What is drug allergy test

What is an allergy blood test?

Allergies are a common and chronic condition that involves the body’s immune system. Normally, your immune system works to fight off viruses, bacteria, and other infectious agents. When you own an allergy, your immune system treats a harmless substance, love dust or pollen, as a threat. To fight this perceived threat, your immune system makes antibodies called immunoglobulin E (IgE).

Substances that cause an allergic reaction are called allergens.

Besides dust and pollen, other common allergens include animal dander, foods, including nuts and shellfish, and certain medicines, such as penicillin. Allergy symptoms can range from sneezing and a stuffy nose to a life-threatening complication called anaphylactic shock. Allergy blood tests measure the quantity of IgE antibodies in the blood. A little quantity of IgE antibodies is normal. A larger quantity of IgE may mean you own an allergy.

Other names: IgE allergy test, Quantitative IgE, Immunoglobulin E, Entire IgE, Specific IgE

When Should You Seek Out Emergency Care?

Symptoms of vertigo are rarely caused by a serious, life-threatening condition.

But, you should visit your doctor immediately or seek emergency medical care if you experience dizziness along with the following:

  1. Numbness or tingling
  2. Fever
  3. Limb weakness
  4. Slurred lecture or trouble speaking
  5. Loss of consciousness
  6. A new, diverse, or severe headache
  7. Double vision or loss of vision
  8. Difficulty walking
  9. Loss of coordination
  10. Hearing loss
  11. Inability to hold food below, or continuous vomiting
What is an allergy blood test?

Allergies are a common and chronic condition that involves the body’s immune system.

Normally, your immune system works to fight off viruses, bacteria, and other infectious agents. When you own an allergy, your immune system treats a harmless substance, love dust or pollen, as a threat. To fight this perceived threat, your immune system makes antibodies called immunoglobulin E (IgE).

Substances that cause an allergic reaction are called allergens. Besides dust and pollen, other common allergens include animal dander, foods, including nuts and shellfish, and certain medicines, such as penicillin.

Allergy symptoms can range from sneezing and a stuffy nose to a life-threatening complication called anaphylactic shock. Allergy blood tests measure the quantity of IgE antibodies in the blood. A little quantity of IgE antibodies is normal. A larger quantity of IgE may mean you own an allergy.

Other names: IgE allergy test, Quantitative IgE, Immunoglobulin E, Entire IgE, Specific IgE

How Common Is It to Experience Vertigo?

Vertigo is considered a common symptom. Almost 40 percent of every adults in the United States experience vertigo at least once during their lifetime, according to the University of California San Francisco Medical Middle.

(1)

Vertigo is typically more prevalent in older people, but it can affect anyone at any age. Women are slightly more likely to experience vertigo symptoms than men.

Other research has shown that about 12.5 million adults over age 65 in the United States own a dizziness or balance issue that significantly interferes with their lives. (2)

According to the National Dizzy and Balance Middle, there are between 5 million and 8 million doctor’s visits for dizziness in the United States each year, and dizziness is a primary reason for an office visit in people over age 75. (2)

There Are Two Main Types of Vertigo

The two main types of vertigo are:

  1. Peripheral Vertigo Peripheral vertigo is caused by a problem in areas of the inner ear or the vestibular nerve, which connects the inner ear and the brain.

    This is the most common type of vertigo.

  2. Central Vertigo Central vertigo happens when there’s a glitch in the brain, particularly in an area of the brain called the cerebellum.

RSV-HSN: A New Type of Vertigo?

Researchers recently discovered a new helpful of vertigo. In a study published in June 2018 in the journal Neurology, scientists called it “recurrent spontaneous vertigo with head-shaking nystagmus” (RSV-HSN).(3)

To diagnose this condition, participants sat in a dark room while an examiner moved their heads forward and then side-to-side for about 15 seconds.

Next, researchers video-recorded the participants’ eye motions. Results showed those with RSV-HSN had eye movements, known as “nystagmus,” that lasted longer than it does in others with vertigo. (3)

The scientists tell that, compared to other types of vertigo, RSV-HSN involves more severe bouts of motion sickness. In the study, people with RSV-HSN had attacks that included nausea, vomiting, headaches, and intolerance of head motions. They experienced symptoms anywhere from a few times a week to once a year.(3)

At this point, the cause of RSV-HSN isn’t known, but the condition does seem to reply well to medication.

(3)

Vertigo: Problems With the Inner Ear

Symptoms of vertigo are often the result of an inner ear (vestibular system) problem. Your inner ear plays a large role in helping you feel balanced.

Inside your ear, there’s a tiny organ called the vestibular labyrinth, which includes semicircular canals that contain fluid and hair-like sensors.

Other structures in the ear, called otolith organs, assist monitor the movement and position of your head in relation to gravity. Otolith organs contain little crystals that make you responsive to gravity.

Sometimes, these crystals can break free and move into the semicircular canals. This can irritate the hair cells within the canals and make them more sensitive to head position changes.

It can permit for untrue messages about your body’s position to be sent to your brain.

Basically, inner ear disorders cause your brain to obtain signals from the inner ear that don’t match up with what your eyes and sensory nerves (nerves that send messages to your brain) receive.

When Should You Call Your Doctor About Your Symptoms?

You should see a doctor if you own vertigo symptoms that come back periodically for more than one week.

(4)

It’s also a excellent thought to see your healthcare provider if you own any type of dizziness that interferes with your daily activities.

Many diverse medical conditions can lead to vertigo. Your physician can recommend tests to assist you figure out what’s causing your symptoms. Sometimes, this process can take a while.

A primary care physician may be capable to diagnose the cause of your vertigo. In fact, about 91 percent of people with vertigo are managed by their general practitioner. (5)

You may also be referred to a specialist, such as an otolaryngologist or a neurologist, to assist diagnose or treat your condition.

What Does It Feel Love to Own Vertigo?

Many people describe vertigo as feeling love the room is spinning.

It might cause you to feel love you’re tilted, rocking, unbalanced, or unsteady.

Sometimes, these unpleasant sensations are worse if you’re standing up, walking, or moving your head around. Numerous people describe these feelings as physically exhausting and taxing. Sometimes, the sensations are so severe that you feel nauseous or experience vomiting.

Symptoms can final a few minutes, or they can persist for hours.

Some people own constant, chronic episodes of vertigo. Others own vertigo symptoms that go away and then reappear after some time.

Usually symptoms of vertigo don’t include light-headedness, fainting, or motion sickness.

Signs and Symptoms of Vertigo Vary From Person to Person

Symptoms of vertigo vary from person to person. Your symptoms might be mild or severe, depending on what’s causing the issue.

Some common signs and symptoms of peripheral vertigo include:

  1. Ringing in the ears
  2. Problems focusing the eyes
  3. Hearing loss in one ear
  4. Feeling love you’re moving or spinning
  5. Balance problems
  6. Dizziness
  7. Sweating
  8. Nausea or vomiting

Central vertigo may cause signs and symptoms, such as:

  1. Cosgrove SE, Vigliani GA, Fowler VG, et al.

    Initial low-dose gentamicin for Staphylococcus aureus bacteremia and endocarditis is nephrotoxic. Clin Infect Dis. 2009;48(6):713-21. [PMID:19207079]

    Comment: Evidence for nephrotoxicity associated with short course synergy dose gentamicin in the treatment of S. aureus bacteremia and endocarditis.

  2. Walters MS, Eggers P, Albrecht V, et al. Vancomycin-Resistant Staphylococcus aureus — Delaware, 2015. MMWR Morb Mortal Wkly Rep. 2015;64(37):1056. [PMID:26402026]

    Comment: Reasons for limited development of VRSA is unclear (compared to enterococci); however, only 14 isolates described since 2001.

    Final four own been from the state of Delaware.

  3. Pallin DJ, Binder WD, Allen MB, et al. Clinical trial: comparative effectiveness of cephalexin plus trimethoprim-sulfamethoxazole versus cephalexin alone for treatment of uncomplicated cellulitis: a randomized controlled trial. Clin Infect Dis. 2013;56(12):1754-62. [PMID:23457080]

    Comment: Interestingly this trial did not propose that adding an agent with activity against CA-MRSA (TMP/SMX) did not substantially improve outcomes [82% cephalexin alone, 85% combination]. This suggests that MRSA is not a common driver of cellulitis in the absence of purulence.

  4. Miller LG, Daum RS, Creech CB, et al.

    Clindamycin versus trimethoprim-sulfamethoxazole for uncomplicated skin infections. N Engl J Med. 2015;372(12):1093-103. [PMID:25785967]

    Comment: As TMP/SMX often thought of as a better staph than strep agent, this study found no diverse between clindamycin or TMP/SMX in those with either abscess, cellulitis or mixed infection. This suggests that fretting about choices if more celllulitic vs. abscess scenarios is not necessary for those with mild-moderate infections.

  5. Thwaites GE, Edgeworth JD, Gkrania-Klotsas E, et al.

    Clinical management of Staphylococcus aureus bacteraemia. Lancet Infect Dis. 2011;11(3):208-22. [PMID:21371655]

    Comment: Important to note that only 16 studies with < 1500 patients in RCTs form basis for guidance in this hard infection. Authors rightly point out that much guideline recommendations are based on observational or limited case studies. Key questions that remain to be answered in their opinion include: 1) How should SAB be defined?, 2) Is identification and removal of infection focus important?

    3) Should every SAB pts own echocardiography? 4) Are glycopeptides equivalent to beta-lactams? 5) Are cephalosporins equivalent to penicillins?, 6) Is teicoplanin as effective as vancomycin? 7) What is the optimum duration of treatment for SAB? 8) Is oral therapy the equivalent to parenteral? 9) Is combination therapy better than monotherapy? 10) what is the role of linezolid, daptomycin and newer antimicrobials?
    Rating: Important

  6. Facial paralysis
  7. Daum RS, Miller LG, Immergluck L, et al.

    A Placebo-Controlled Trial of Antibiotics for Smaller Skin Abscesses. N Engl J Med. 2017;376(26):2545-2555. [PMID:28657870]

  8. Dhand A, Bayer AS, Pogliano J, et al. Use of antistaphylococcal beta-lactams to increase daptomycin activity in eradicating persistent bacteremia due to methicillin-resistant Staphylococcus aureus: role of enhanced daptomycin binding. Clin Infect Dis. 2011;53(2):158-63. [PMID:21690622]

    Comment: Authors capable to clear persistent bacteremia in 7 pts with combination of daptomycin and oxacillin or nafcillin (2g IV q4h) in seven patients. Mechanism not entirely clear but may be due to enhanced membrane binding of daptomycin in the presence of the beta-lactam.

  9. Vos FJ, Kullberg BJ, Sturm PD, et al.

    Metastatic infectious disease and clinical outcome in Staphylococcus aureus and Streptococcus species bacteremia. Medicine (Baltimore). 2012;91(2):86-94. [PMID:22391470]

    Comment: Study of 115 patients with staph or strep bacteremia using FDG-PET/CT technology looking for metastatic infections found foci in 84 of 115 (73%) patients: endocarditis (22 cases), endovascular infections (19 cases), pulmonary abscesses (16 cases), and spondylodiscitis (11 cases) were diagnosed most frequently.

    Signs or symptoms directing a diagnostic work-up were only present in 41%, suggesting that additional studies may be helpful even in absence of specific findings: for example in this study PET was the first to detect problems in 30%.

  10. Weak limbs
  11. Talan DA, Mower WR, Krishnadasan A, et al. Trimethoprim-Sulfamethoxazole versus Placebo for Uncomplicated Skin Abscess. N Engl J Med. 2016;374(9):823-32. [PMID:26962903]

    Comment: Rather surprising results from this study that is in contrast to the «no antibiotic needed» dogma for uncomplicated, drained S aureus abscesses.

    Study suggested higher cure rates in 507 of 630 participants (80.5%) in the trimethoprim-sulfamethoxazole group versus 454 of 617 participants (73.6%) in the placebo group (difference, 6.9 percentage points; 95% confidence interval [CI], 2.1 to 11.7; P=0.005).

  12. Holland TL, Raad I, Boucher HW, et al. Effect of Algorithm-Based Therapy vs Usual Care on Clinical Success and Serious Adverse Events in Patients with Staphylococcal Bacteremia: A Randomized Clinical Trial. JAMA. 2018;320(12):1249-1258. [PMID:30264119]

    Comment: Randomized trial of 509 adults with staphylococcal bacteremia, use of an algorithm compared with usual care resulted in a clinical success rate of 82.0% vs 81.5%, respectively—showing little difference and similar serious adverse events occurred in 32.5% vs 28.3% of patients, a difference that was not statistically significant but with wide confidence intervals.

    The trial used 14 +/- 2 d for short course vs. 28-42 days for complicated. Trial suggests that staphylococcal bacteremia can be treated by the algorithm if diagnostic and therapeutic recommendations are followed. An exciting sidebar is in the uncomplicated, short-course group, the failure rate was 25-30%.

  13. DiNubile MJ. Short-course antibiotic therapy for right-sided endocarditis caused by Staphylococcus aureus in injection drug users. Ann Intern Med. 1994;121(11):873-6. [PMID:7978701]

    Comment: A review of the option of shorter course antibiotic therapy for right-sided heart infections in injection drug users.

  14. Wunderink RG, Niederman MS, Kollef MH, et al. Linezolid in methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a randomized, controlled study. Clin Infect Dis. 2012;54(5):621-9. [PMID:22247123]

    Comment: Fairly large trial in a hard to study condition. RCT examined linezolid (600 mg every 12 hours) or vancomycin (15 mg/kg every 12 hours) x 7-14d. Enrolled pts numbered 1184, 448 (linezolid, n = 224; vancomycin, n = 224) were included in the mITT and 348 (linezolid, n = 172; vancomycin, n = 176) in the PP population.

    In the PP population, 95 (57.6%) of 165 linezolid-treated patients and 81 (46.6%) of 174 vancomycin-treated patients achieved clinical success at EOS (95% confidence interval for difference, 0.5%-21.6%; P = .042). Howvever, all-cause 60-day mortality was similar (linezolid, 15.7%; vancomycin, 17.0%), as was incidence of adverse events. Nephrotoxicity occurred more frequently with vancomycin (18.2%; linezolid, 8.4%). This study suggests that the PK/PD elements favoring linezolid may in fact own clinical efficacy favorable over vancomycin but the larger 60d picture is not telling.

    For the extremely ill with potential for added complications such as renal failure, linezolid may be the better option.

  15. Naimi TS, LeDell KH, Como-Sabetti K, et al. Comparison of community- and health care-associated methicillin-resistant Staphylococcus aureus infection. JAMA. 2003;290(22):2976-84.

    What is drug allergy test

    [PMID:14665659]

    Comment: A study that elucidates the clinical and microbiologic differences between healthcare-associated MRSA and community-associated MRSA.
    Rating: Important

  16. Cosgrove SE, Carroll KC, Perl TM. Staphylococcus aureus with reduced susceptibility to vancomycin. Clin Infect Dis. 2004;39(4):539-45. [PMID:15356818]

    Comment: Review of the epidemiology, diagnosis, and management of patients with S. aureus with reduced susceptibility to vancomycin.
    Rating: Important

  17. Double vision
  18. Tranter HS. Foodborne staphylococcal illness. Lancet.

    1990;336(8722):1044-6. [PMID:1977028]

    Comment: A review of GI tract infections caused by ingestion of certain toxin-producing strains of S. aureus.

    What is drug allergy test

  19. Kaasch AJ, Barlow G, Edgeworth JD, et al. Staphylococcus aureus bloodstream infection: a pooled analysis of five prospective, observational studies. J Infect. 2014;68(3):242-51. [PMID:24247070]

    Comment: Five cohorts of S. aureus bacteremia with adjusted HR mortality in this group of 3346 with 30d mortality = 21%, 90d mortality = 29%.

  20. Carr DR, Stiefel U, Bonomo RA, et al. A Comparison of Cefazolin Versus Ceftriaxone for the Treatment of Methicillin-Susceptible Staphylococcus aureus Bacteremia in a Tertiary Care VA Medical Middle. Open Forum Infect Dis. 2018;5(5):ofy089.

    [PMID:30568987]

  21. Fowler VG, Boucher HW, Corey GR, et al. Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus. N Engl J Med. 2006;355(7):653-65. [PMID:16914701]

    Comment: Recent publication demonstrating that daptomycin is not inferior to standard therapy in the treatment of S. aureus bacteremia and right-sided endocarditis.
    Rating: Important

  22. Figueroa DA, Mangini E, Amodio-Groton M, et al. Safety of high-dose intravenous daptomycin treatment: three-year cumulative experience in a clinical program. Clin Infect Dis.

    2009;49(2):177-80. [PMID:19500039]

    Comment: Single middle study evaluating the safety of higher doses of daptomycin.
    Rating: Important

  23. del Río A, Gasch O, Moreno A, et al. Efficacy and safety of fosfomycin plus imipenem as save therapy for complicated bacteremia and endocarditis due to methicillin-resistant Staphylococcus aureus: a multicenter clinical trial. Clin Infect Dis. 2014;59(8):1105-12. [PMID:25048851]

    Comment: Available in some European and other countries, this little study examined S aureus bacteremia or endocarditis and found that fosfomycin [2g IV q 6] + imipenem appeared to be helpful in those failing regimens including vancomcyin, daptomycin and others.

    Success rate was 69% of the 16 patients.

  24. Heldman AW, Hartert TV, Ray SC, et al. Oral antibiotic treatment of right-sided staphylococcal endocarditis in injection drug users: prospective randomized comparison with parenteral therapy. Am J Med. 1996;101(1):68-76.

    What is drug allergy test

    [PMID:8686718]

    Comment: A study comparing standard therapy for right-sided endocarditis to oral ciprofloxacin and rifampin for 4 weeks that demonstrates the efficacy of the oral regimen.

  25. Nambiar K, Seifert H, Rieg S, et al. Survival following Staphylococcus aureus bloodstream infection: A prospective multinational cohort study assessing the impact of put of care. J Infect. 2018;77(6):516-525. [PMID:30179645]

    Comment: Among diverse hospitals, mortality rates among the pooled 1851 patients with a median age of 66 years (64% male) were analyzed.

    Crude 90-day mortality differed significantly between hospitals (range 23-39%) which authors attributed to numerous factors.

  26. Difficulty swallowing
  27. Markowitz N, Quinn EL, Saravolatz LD. Trimethoprim-sulfamethoxazole compared with vancomycin for the treatment of Staphylococcus aureus infection. Ann Intern Med. 1992;117(5):390-8. [PMID:1503330]

    Comment: A study of 101 injection drug users with S. aureus infection of whom 65% were bacteremic.

    The success rate for therapy of MRSA infections was equivalent for the TMP-SMX and vancomycin groups, although vancomycin was marginally more successful as a therapy in the non-MRSA group. The authors thus suggests that TMP-SMX may be a viable alternative to vancomycin for MRSA infection in this group of patients. Failures with TMP/SMX were seen only in the group with endocarditis but not those with straight (or supposedly straight) bacteremia.
    Rating: Important

  28. Rieg S, von Cube M, Kaasch A, et al.

    Investigating the impact of early valve surgery on survival in Staphylococcus aureus infective endocarditis using a marginal structural model approach — results of a large prospectively evaluated cohort. Clin Infect Dis. 2018. [PMID:30346527]

    Comment: Although early valve surgery advocated by numerous, this series did not discover significant benefit.

  29. Eye movement difficulties
  30. Fowler VG, Li J, Corey GR, et al. Role of echocardiography in evaluation of patients with Staphylococcus aureus bacteremia: experience in 103 patients. J Am Coll Cardiol. 1997;30(4):1072-8. [PMID:9316542]

    Comment: A study demonstrating the presence of endocarditis in 25% of patients with S.

    aureus bacteremia when evaluated with TEE.
    Rating: Important

  31. Simor AE. Staphylococcal decolonisation: an effective strategy for prevention of infection? Lancet Infect Dis. 2011;11(12):952-62. [PMID:22115070]

    Comment: Best data regarding decolonization efficacy exists in pre-surgical patients and those on dialysis. Efficacy for decreasing CA-MRSA recurrent infections doesn’t yet exist in robust fashion.
    Rating: Important

  32. Slurred speech
  33. Berbari EF, Kanj SS, Kowalski TJ, et al.

    Executive Summary: 2015 Infectious Diseases Society of America (IDSA) Clinical Practice Guidelines for the Diagnosis and Treatment of Native Vertebral Osteomyelitis in Adults. Clin Infect Dis. 2015;61(6):859-63. [PMID:26316526]

    Comment: Guidance document suggesting 6 wks of parenteral or highly bioavailable oral therapy for native (no hardware) vertebral osteomyelitis. First line choices for MSSA, recs include nafcillin, oxacillin, cefazolin or ceftriaxone.

    For MRSA, vancomycin or daptomycin.

  34. Song KH, Jung SI, Lee S, et al. Inoculum effect of methicillin-susceptible Staphylococcus aureus against broad-spectrum beta-lactam antibiotics. Eur J Clin Microbiol Infect Dis. 2019;38(1):67-74. [PMID:30269181]

    Comment: Among 302 MSSA isolates in this South Korean study representing hospital isolates, 254 (84.1%) were positive for blaZ; types A, B, C and D were 13.6%, 26.8%, 43.4% and 0.3%, respectively. Mean HI MICs of every tested antibiotics were significantly increased and increases in HI MIC of piperacillin/tazobactam (HI, 48.14 ± 4.08 vs.

    SI, 2.04 ± 0.08 mg/L, p <  0.001) and ampicillin/sulbactam (HI, 24.15 ± 1.27 vs. SI, 2.79 ± 0.11 mg/L, p <  0.001) were most prominent. No MSSA isolates exhibited meropenem InE, and few isolates exhibited cefepime (0.3%) and ceftriaxone (2.3%) InE, whereas 43.0% and 65.9% of MSSA isolates exhibited piperacillin/tazobactam and ampicillin/sulbactam InE, respectively. About 93% of type C blaZ versus 45% of non-type C exhibited ampicillin/sulbactam InE (p <  0.001) and 88% of type C blaZ versus 9% of non-type C exhibited piperacillin/tazobactam InE (p <  0.001).

    A large proportion of MSSA clinical isolates, especially those positive for type C blaZ, showed marked ampicillin/sulbactam InE and piperacillin/tazobactam.

  35. von Eiff C, Becker K, Machka K, et al. Nasal carriage as a source of Staphylococcus aureus bacteremia. Study Group. N Engl J Med. 2001;344(1):11-6. [PMID:11136954]

    Comment: A German study indicating that S. aureus bacteremia appears to frequently be caused by strains of S. aureus colonizing the patient’s own nasal mucosa. An accompanying editorial emphasizes the importance of attempting to eradicate this colonization in order to control nosocomial infections, but highlights the failure of most currently used agents to achieve this goal (N Engl J Med 2001; 344: 55-57)

  36. Paul M, Bishara J, Yahav D, et al.

    Trimethoprim-sulfamethoxazole versus vancomycin for severe infections caused by meticillin resistant Staphylococcus aureus: randomised controlled trial. BMJ. 2015;350:h2219. [PMID:25977146]

    Comment: For those with severe infections including bacteremia especially, TMP/SMX did not acheive non-inferiority compared to vancomycin. Multivariable logistic regression had trimethoprim-sulfamethoxazole significantly associated with treatment failure (adjusted odds ratio 2.00, 1.09 to 3.65).

    The 30 day mortality rate was 32/252 (13%), with no significant difference between arms. Among patients with bacteraemia, 14/41 (34%) treated with trimethoprim-sulfamethoxazole and 9/50 (18%) with vancomycin died (risk ratio 1.90, 0.92 to 3.93).

  37. Lee BK, Crossley K, Gerding DN. The association between Staphylococcus aureus bacteremia and bacteriuria. Am J Med. 1978;65(2):303-6. [PMID:686015]

    Comment: The classic paper describing the presence of S. aureus bacteriuria in 27% of patients with S.

    aureus bacteremia in the absence of obvious renal infection.

Living With Vertigo Can Be Challenging

Vertigo can impact your daily life. If your episodes are frequent or severe, you may not be capable to work, drive, or act out other tasks.

Typically, people with persistent vertigo are advised not to drive or operate machinery because these activities can pose dangers to the individuals and others.

Vertigo can also lead to falls, which may cause injuries.

Falling is particularly a concern for older people, who are more prone to bone fractures and other complications. In fact, falling is the number one cause of fatal and nonfatal accidents in older Americans, according to the National Council on Aging. (6)

Living with vertigo can be frustrating. Your episodes might be unpredictable and sporadic. Some days, you may not experience any symptoms, while other days, you might own debilitating bouts of dizziness.

The excellent news is there are effective treatment options that can improve your symptoms and quality of life.

In most cases, people with allergies develop mild to moderate symptoms, such as watery eyes, a runny nose or a rash.

But sometimes, exposure to an allergen can cause a life-threatening allergic reaction known as anaphylaxis. This severe reaction happens when an over-release of chemicals puts the person into shock. Allergies to food, insect stings, medications and latex are most frequently associated with anaphylaxis.

A second anaphylactic reaction, known as a biphasic reaction, can happen as endless as 12 hours after the initial reaction.

Call 911 and get to the nearest emergency facility at the first sign of anaphylaxis, even if you own already istered epinephrine, the drug used to treat severe allergic reactions.

Just because an allergic person has never had an anaphylactic reaction in the past to an offending allergen, doesn’t mean that one won’t happen in the future. If you own had an anaphylactic reaction in the past, you are at risk of future reactions.

Sulfatrim S/S

Generic Name: Sulfonamides and Trimethoprim
This monograph includes information on the following:

1) Sulfadiazine and Trimethoprim*
2) Sulfamethoxazole and Trimethoprim

BAN:
{04}Sulfadiazine—Sulphadiazine
Sulfamethoxazole—Sulphamethoxazole

JAN:
{04}Sulfamethoxazole—Acetylsulfamethoxazole
Sulfamethoxazole—Sulfamethoxazole sodium

VA CLASSIFICATION
Primary: AM650

Commonly used brand name(s): Apo-Sulfatrim2; Apo-Sulfatrim DS2; Bactrim2; Bactrim DS2; Bactrim I.V.2; Bactrim Pediatric2; Cofatrim Forte2; Coptin1; Coptin 11; Cotrim2; Cotrim DS2; Cotrim Pediatric2; Novo-Trimel2; Novo-Trimel D.S.2; Nu-Cotrimox2; Nu-Cotrimox DS2; Roubac2; Septra2; Septra DS2; Septra Grape Suspension2; Septra I.V.2; Septra Suspension2; Sulfatrim2; Sulfatrim Pediatric2; Sulfatrim S/S2; Sulfatrim Suspension2; Sulfatrim-DS2.

Other commonly used names are

• Cotrimazine Sulfadiazine and Trimethoprim

• Cotrimoxazole Sulfamethoxazole and Trimethoprim

• SMZ-TMP Sulfamethoxazole and Trimethoprim
Note:For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

*Not commercially available in the U.S.

Category:

Antibacterial (systemic)—Sulfadiazine and Trimethoprim; *Sulfamethoxazole and Trimethoprim;

Antiprotozoal—Sulfamethoxazole and Trimethoprim;

Indications

Note:Bracketed information in the Indications section refers to uses that are not included in U.S.

product labeling.

General considerations
Sulfonamides, such as sulfadiazine and sulfamethoxazole, used together with trimethoprim, produce synergistic antibacterial activity. {14}{156} Sulfadiazine and sulfamethoxazole own equal antibacterial properties, covering the same spectrum of activity. {14}These sulfonamides, in combination with trimethoprim, are athletic in vitro against numerous gram-positive and gram-negative aerobic organisms. They own minimal activity against anaerobic bacteria.

{104} Susceptible gram-positive organisms include numerous Staphylococcus aureus , including some methicillin-resistant strains, S. saprophyticus , some group A beta-hemolytic streptococci, Streptococcus agalactiae , and most but not every strains of S. pneumoniae . {104} Gram-negative organisms that are susceptible include Escherichia coli, numerous Klebsiella species, Citrobacter diversus and C.

fruendii , Enterobacter species, Salmonella species, Shigella species, Haemophilus influenzae , including some ampicillin-resistant strains, H. ducreyi , Morganella morganii , Proteus vulgaris and P. mirabilis , and some Serratia species. {104} Sulfonamide and trimethoprim combinations also own activity against Acinetobacter species, Pneumocystis carinii, Providencia rettgeri , P. stuarti , Aeromonas , Brucella , and Yersinia species. {104} They are also generally athletic against Neisseria meningitidis , Branhamella (Moraxella) catarrhalis , and some, but not every, N.

gonorrhoeae . {104}Pseudomonas aeruginosa is generally resistant, but P. cepacia and P. maltophilia may be sensitive.

What is drug allergy test

{104}

The major difference between sulfadiazine and sulfamethoxazole exists in their respective pharmacokinetics. The primary distinction is that sulfadiazine is metabolized to a much lesser extent than is sulfamethoxazole. {14}{152}{156} This allows for a higher urinary concentration of unchanged sulfadiazine {152}{156}{164}, as well as an increased risk of crystalluria when it is istered in high doses {152}; the antibacterial urinary concentration of sulfadiazine is maintained over a 24-hour interval, allowing for once-a-day dosing in adults.

{150}{164} Also, sulfadiazine achieves higher concentrations in the bile and cerebrospinal fluid. {14}{151}

Accepted

Bronchitis (treatment)—Oral sulfamethoxazole and trimethoprim combination is indicated in adults in the treatment of acute exacerbations of chronic bronchitis caused by susceptible organisms. {03}{05}{18}{22}{38}{168}{170}

Enterocolitis, Shigella species (treatment) —Oral and parenteral sulfamethoxazole and trimethoprim combinations are indicated in the treatment of enterocolitis caused by susceptible strains of Shigella flexneri and S.

sonnei.{01}{03}{05}{21}{38}{168}{169}{170}{171}

Otitis media, acute (treatment)—Oral sulfamethoxazole and trimethoprim combination is indicated in the treatment of acute otitis media caused by susceptible organisms in children. {03}{05}{21}{38}{168}{170}

Pneumonia, Pneumocystis carinii (prophylaxis)1—Oral sulfamethoxazole and trimethoprim combination is indicated in the prophylaxis of Pneumocystis carinii pneumonia (PCP) in patients who are immunocompromised and considered to be at increased risk of developing PCP, including patients with acquired immunodeficiency syndrome (AIDS).

{168}{170} It is considered to be the treatment of choice for this indication. {94} Sulfamethoxazole and trimethoprim combination is indicated in both secondary prophylaxis (patients who own already had at least one episode of PCP), and primary prophylaxis (HIV-infected adults with a CD4 lymphocyte count less than or equal to 200 cells per cubic millimeter and/or less than 20% of entire lymphocytes; every children born to HIV-infected mothers, beginning at 4 to 6 weeks of age, and subsequent prophylaxis given as sure on the basis of age-specific CD4 lymphocyte count{94}) of PCP. {03}{05}{53}{54}{55}{56}{57}{60}{61}{113}

Pneumonia, Pneumocystis carinii (treatment) —Oral and parenteral sulfamethoxazole and trimethoprim combinations are indicated as primary agents in the treatment of Pneumocystis carinii pneumonia (PCP) in immunocompromised patients, including patients with acquired immunodeficiency syndrome (AIDS).

{01}{03}{05}{18}{95}{168}{169}{170}{171}Pentamidine is considered an alternative agent for PCP.

Traveler’s diarrhea (treatment)—Oral sulfamethoxazole and trimethoprim combination is indicated in the treatment of traveler’s diarrhea caused by susceptible strains of enterotoxigenic Escherichia coli and Shigella species. {03}{18}{38}{138}{139}{168}{170}

Urinary tract infections, bacterial (treatment)— Sulfadiazine and trimethoprim combination {150}{157}{158}{159}{160}{161}{162}{163}{164} and oral and parenteral sulfamethoxazole and trimethoprim combinations {01}{03}{22}{38}{140}{141}{168}{169}{170}{171} are indicated in the treatment of urinary tract infections caused by susceptible organisms.

[Biliary tract infections (treatment)]—Sulfamethoxazole and trimethoprim combination is used in the treatment of biliary tract infections caused by susceptible organisms.

{38}

[Bone and joint infections (treatment)]—Sulfamethoxazole and trimethoprim combination is used in the treatment of bone and joint infections caused by susceptible organisms. {22}{38}

[Chancroid (treatment)]1—Sulfamethoxazole and trimethoprim combination is used as an alternative agent in the treatment of chancroid. {38}{147}{148}{149}

[Chlamydial infections (treatment) ]1—Sulfamethoxazole and trimethoprim combination is used as an alternative agent in the treatment of chlamydial infections.

{37}

[Cyclospora infections (treatment) ]1—Sulfamethoxazole and trimethoprim combination is used in the treatment of diarrhea caused by Cyclospora cayetanensis , but may not completely eradicate the organism. {106}{107}{108}{109}

[Endocarditis, bacterial (treatment) ]1—Sulfamethoxazole and trimethoprim combination is used as an alternative agent in the treatment of bacterial endocarditis caused by susceptible organisms. {37}{38}

[Gonorrhea, endocervical and urethral, uncomplicated (treatment)]—Sulfamethoxazole and trimethoprim combination is used as an alternative agent in the treatment of gonorrhea caused by susceptible organisms.

{22}{38}{146}

[Granuloma inguinale (treatment)]1—Sulfamethoxazole and trimethoprim combination is used as an alternative agent in the treatment of granuloma inguinale. {37}{145}

[HIV-related infections in Africa (prophylaxis)]1—Sulfamethoxazole and trimethoprim combination is used in the prophylaxis of HIV-related infections in Africa{172}{173}{174}.
—Given the large number of patients with HIV-related infections throughout Africa and the high mortality they experience, sulfamethoxazole and trimethoprim combination prophylaxis if widely applicable and implemented could significantly affect care and survival (i.e., could significantly lower morbidity and mortality) among HIV-infected patients in Africa{172}{173}{174}.

[Isosporiasis (prophylaxis and treatment) ]1—Sulfamethoxazole and trimethoprim combination is used in the prophylaxis and treatment of isosporiasis caused by Isospora belli .

{38}{39}{40}{104}

[Lymphogranuloma venereum (treatment) ]1—Sulfamethoxazole and trimethoprim combination is used in the treatment of lymphogranuloma venereum. {38}{104}

[Meningitis (treatment)]—Sulfamethoxazole and trimethoprim combination is used as an alternative agent in the treatment of meningitis caused by susceptible organisms. {37}{38}

[Nocardiosis (treatment)]—Sulfamethoxazole and trimethoprim combination is used in the treatment of nocardiosis. {22}{38}{104}{137}

[Paracoccidioidomycosis (treatment) ]1—Sulfamethoxazole and trimethoprim combination is used in the treatment of paracoccidioidomycosis.

{38}

[Paratyphoid fever (treatment)] or
[Typhoid fever (treatment)]—Sulfamethoxazole and trimethoprim combination is used as an alternative agent in the treatment of paratyphoid and typhoid fevers caused by susceptible strains. {22}{38}

[Septicemia, bacterial (treatment)]—Sulfamethoxazole and trimethoprim combination is used as an alternative agent in the treatment of bacterial septicemia caused by susceptible organisms.

{37}{38}

[Sinusitis (treatment)]1—Sulfamethoxazole and trimethoprim combination is used in the treatment of sinusitis caused by susceptible organisms. {38}{103}{104}

[Skin and soft tissue infections (treatment)]—Sulfamethoxazole and trimethoprim combination is used in the treatment of skin and soft tissue infections, including burn wound infections caused by susceptible organisms. {22}

[Toxoplasmosis (prophylaxis)]1—Sulfamethoxazole and trimethoprim combination is used in the primary prophylaxis of toxoplasmosis in patients with AIDS. {38}{94}{95}{100}{114}{115}{167}

[Urinary tract infections, bacterial (prophylaxis)]1—Sulfamethoxazole and trimethoprim combination is used in the prophylaxis of bacterial urinary tract infections.

{37}{102}{142}

[Whipple’s disease (treatment)]1—Sulfamethoxazole and trimethoprim combination is used in the treatment of Whipple’s disease. {104}{105}{109}{110}{111}{112}

—Not every strains of a specific organism may be susceptible to sulfonamide and trimethoprim combinations.

Unaccepted
Sulfamethoxazole and trimethoprim combination is not indicated for prophylaxis or prolonged therapy in otitis media. {03}{168}{170} Sulfamethoxazole and trimethoprim combination is not effective in the treatment of syphilis{37}{38} andUreaplasm urealyticum{37}.

Sulfamethoxazole and trimethoprim combination should not be used in the treatment of group A beta-hemolytic streptococcal tonsillopharyngitis since it may not eradicate streptococci and therefore may not prevent sequelae such as rheumatic fever.

{01}{05}{37}

1Not included in Canadian product labeling.

Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
Sulfadiazine: 250.28 {04}
Sulfamethoxazole: 253.28 {04}
Trimethoprim: 290.32 {04}

Mechanism of action/Effect:

Sulfonamides:

Sulfonamides are broad-spectrum, bacteriostatic anti-infectives.

{22} They are structural analogs of para-aminobenzoic acid (PABA) and competitively inhibit a bacterial enzyme, dihydropteroate synthetase, that is responsible for incorporation of PABA into dihydrofolic acid, the immediate precursor of folic acid. {23} This blocks the synthesis of dihydrofolic acid and decreases the quantity of metabolically athletic tetrahydrofolic acid, a cofactor for the synthesis of purines, thymidine, and DNA. {37}

Susceptible bacteria are those that must synthesize folic acid.

Mammalian cells require preformed folic acid and cannot synthesize it. {37}{38} The action of sulfonamides is antagonized by PABA and its derivatives (e.g., procaine and tetracaine) and by the presence of pus or tissue breakdown products, which provide the necessary components for bacterial growth. {23}

Trimethoprim:

Trimethoprim is a bacteriostatic lipophilic feeble base structurally related to pyrimethamine. It binds to and reversibly inhibits the bacterial enzyme dihydrofolate reductase, selectively blocking conversion of dihydrofolic acid to its functional form, tetrahydrofolic acid. {03}{22}{37} This depletes folate, an essential cofactor in the biosynthesis of nucleic acids, resulting in interference with bacterial nucleic acid and protein production.

{23} Bacterial dihydrofolate reductase is approximately 50,000 to 100,000 times more tightly bound by trimethoprim than is the corresponding mammalian enzyme. {37}{38}

Trimethoprim exerts its effect at a step in the folate biosynthesis immediately subsequent to the one at which sulfonamides exert their effect. When trimethoprim is istered concurrently with sulfonamides, synergism occurs, which is attributed to inhibition of tetrahydrofolate production at 2 sequential steps in its biosynthesis. {22}{23}{37}

Absorption:

Oral—Sulfonamides and trimethoprim are rapidly and well absorbed (70 to 100%).

{22}{151}{152}

Distribution:

Sulfonamides:

Widely distributed throughout body tissues and fluids, including pleural {01}{23}{165}, peritoneal {01}{23}{165}, synovial {01}{23}{165}, middle ear {01}{23}, and ocular fluids {01}{23}{165}, as well as nasal secretions {154}, sputum {01}{23}, and prostate {152}, lymph {153}, and renal tissue {152}.

Sulfadiazine is distributed throughout entire body water {23}{37} and achieves higher concentrations in bile than does sulfamethoxazole {14}. Sulfonamides readily cross the placenta and are distributed into breast milk, also. {01}{23}{37} Sulfonamides penetrate into the cerebrospinal fluid (CSF) with CSF concentrations of sulfadiazine reaching 32 to 65% {151} and those of sulfamethoxazole reaching 14 to 30% of the corresponding blood concentrations. {23}{27}{37}{38} Sulfonamides may be detected in the urine in approximately 30 minutes.

{23}

Trimethoprim:

Rapidly and widely distributed to various tissues and fluids, including kidneys, liver, spleen, bronchial secretions, saliva, sputum, middle ear, and prostatic tissue and fluid. {01}{23}{37} Trimethoprim is also distributed into bile, aqueous humor, bone, mucosa, and seminal fluid. {37}{38} It penetrates into the CSF with CSF concentrations reaching 20 to 40% of corresponding plasma concentrations. {37}{38} Trimethoprim crosses the placenta and is distributed into breast milk. {01}{37}

Urine solubility:

Sulfadiazine: Acetylated sulfadiazine has the least solubility, followed by sulfadiazine.

{152}

Sulfamethoxazole: Acetylated sulfamethoxazole is more soluble than sulfadiazine, but less soluble than sulfamethoxazole. {152}

Vol D:

Sulfadiazine: Approximately 33.7 liters. {165}

Sulfamethoxazole: Approximately 0.21 liters per kg of body weight (L/kg). {23}{37}

Trimethoprim: Approximately 1.8 L/kg. {23}{37}

Protein binding:

Sulfonamides:

Sulfonamides compete with bilirubin for binding to albumin.

Kernicterus may develop in premature infants or neonates. {37} Binding is decreased in patients with severely impaired renal function. {38} Only free, unbound drug has antibacterial activity. {27}

Sulfadiazine: Moderate (38 to 56%). {151}{152}

Sulfamethoxazole: Moderate to high (60 to 70%). {01}{23}{38}

Trimethoprim:

Moderate (40 to 45%).

{01}{23}{24}{37} Protein binding does not significantly decrease in patients with uremia. {38}

Biotransformation:

Sulfonamides—Hepatic; primarily by acetylation to inactive metabolites, which retain the toxicity of the parent compound. {23} Some hepatic glucuronide conjugation may happen. {37}

Trimethoprim—Hepatic; 10 to 20% metabolized to inactive metabolites by O-demethylation, ring N-oxidation, and alpha-hydroxylation; metabolites may be free or conjugated. {24}

Half-life:

Sulfadiazine:

Normal renal function: 9 to 13.7 hours.

{152}{155}{156}

Renal failure: Approximately 34 hours. {23}{38}

Sulfamethoxazole:

Normal renal function: 10 to 12 hours. {01}{03}{22}{23}{37}{38}

Creatinine clearance less than 10 mL per minute (mL/min) (0.17 mL per second [mL/sec]): 18 to 50 hours. {38}{118}

Trimethoprim:

Normal renal function: 8 to 10 hours. {01}{03}{22}{23}{24}{37}{152}{156}

Creatinine clearance less than 10 mL/min (0.17 mL/sec): Approximately 24 hours.

{38}{118}

Time to peak serum concentration

Oral:

Sulfadiazine: 2.7 to 4 hours. {152}{155}{156}

Sulfamethoxazole: 2 to 4 hours. {22}{23}

Trimethoprim: 1 to 4 hours. {03}{22}{23}{37}{38}{156}

Peak serum concentration:

Sulfadiazine:

Single 820-mg dose: 27.5 to 31.7 mcg/mL.

{152}{155}{156}

Sulfamethoxazole:

Oral, 800 mg twice a day: Approximately 40 mcg/mL. {23}{38}

Intravenous, 800 mg three times a day: Approximately 106 mcg/mL. {37}{38}

Trimethoprim:

Oral, 160 mg twice a day: Approximately 2 to 2.4 mcg/mL. {23}{38}{156}

Intravenous, 160 mg three times a day: Approximately 9 mcg/mL. {37}{38}

Elimination:

Sulfonamides—
Renal, by glomerular filtration, with some tubular secretion {01} and reabsorption of both athletic medication and metabolites.

Excretion is increased in alkaline urine {37}{38}.

Percent of medication unchanged in the urine—
Sulfadiazine: 43 to 58% in 24 hours. {151}{155}{156}
Sulfamethoxazole: 20 to 40%. {23}{37}

Little amounts are excreted in the feces, bile, and other body secretions. {38}

In dialysis—
Sulfamethoxazole is removed from the blood by hemodialysis.

{21}{37} However, peritoneal dialysis is not effective. {27}{118}

Trimethoprim—
Renal, 40 to 60% excreted within 24 hours, primarily by glomerular filtration and tubular secretion {03}{22}{23}{37}{156}; of this quantity, 80 to 90% is excreted unchanged and the remainder is excreted as inactive metabolites. {37} Excretion is increased in acid urine and decreased in alkaline urine.

{38}
Little amounts are excreted in the feces and bile. {22}

In dialysis—
Significant amounts of trimethoprim are removed from the blood by hemodialysis {21}, requiring a full maintenance dose after dialysis. Peritoneal dialysis is not effective in removing trimethoprim from the blood. {118}

Precautions to Consider

Cross-sensitivity and/or related problems

Patients allergic to sulfonamides or trimethoprim may be allergic to sulfonamide and trimethoprim combinations.

{01}{150}

Patients allergic to furosemide, thiazide diuretics, sulfonylureas, or carbonic anhydrase inhibitors may be allergic to sulfonamides also. {25}{26}

Patients sensitive to sulfites may own an allergic reaction to Bactrim I.V. since it contains sodium metabisulfite. {01}

Carcinogenicity

Sulfamethoxazole and trimethoprim—Long-term studies to assess the carcinogenic potential of sulfamethoxazole and trimethoprim combination own not been done.

{01}

Mutagenicity

Sulfamethoxazole and trimethoprim—Bacterial mutagenicity studies with sulfamethoxazole and trimethoprim combination own not been done. Trimethoprim has not been shown to be mutagenic in the Ames assay. Studies in human leukocytes cultured in vitro with sulfamethoxazole and trimethoprim combination, using concentrations that exceeded therapeutic serum concentrations, own not shown that sulfamethoxazole and trimethoprim combination causes chromosomal damage. {01}

Pregnancy/Reproduction
Fertility—
Sulfamethoxazole and trimethoprim: Studies in rats, given oral doses as high as 70 mg of trimethoprim per kg of body weight (mg/kg) and 350 mg/kg of sulfamethoxazole daily, own not shown that sulfamethoxazole or trimethoprim causes any adverse effects on fertility or general reproductive performance.

{01}

Pregnancy—
Sulfadiazine: FDA Pregnancy Category C. {151}

Sulfamethoxazole and trimethoprim: Sulfamethoxazole and trimethoprim cross the placenta. Adequate and well-controlled studies in humans own not been done. {01} However, prophylaxis for Pneumocystis carinii pneumonia (PCP) is recommended in HIV-infected pregnant women. {94} In one retrospective study in 186 women who received placebo or sulfamethoxazole and trimethoprim combination during pregnancy, the incidence of congenital abnormalities was lower (3.3% versus 4.5%) in the sulfamethoxazole and trimethoprim combination–treated group.

No abnormalities were reported in the 10 children whose mothers received sulfamethoxazole and trimethoprim combination during the first trimester. In another study, no congenital abnormalities were reported in 35 children whose mothers received sulfamethoxazole and trimethoprim combination at the time of conception or shortly thereafter. However, sulfamethoxazole and trimethoprim may interfere with folic acid metabolism in the fetus. {01}

Studies in rats given oral doses of 200 mg/kg of trimethoprim and 533 mg/kg of sulfamethoxazole own shown that sulfamethoxazole causes teratogenic effects (primarily cleft palates).

However, doses of 192 mg/kg of trimethoprim and 512 mg/kg of sulfamethoxazole, when istered separately, did not cause cleft palates in rats. Doses of 88 mg/kg of trimethoprim and 355 mg/kg of sulfamethoxazole own been shown to cause cleft palates when istered concurrently. {01} Studies in rabbits given doses of trimethoprim 6 times the usual human therapeutic dose own shown that trimethoprim causes an increase in the number of dead, resorbed, and malformed fetuses.

{01}

FDA Pregnancy Category C. {01}

Labor and delivery—

Sulfonamides are not recommended at term since they may cause jaundice, hemolytic anemia, and kernicterus in the newborn. {26}{38}

Breast-feeding

Sulfonamides—Sulfonamides are distributed into breast milk. {01} Use is not recommended in nursing women since sulfonamides may cause kernicterus in nursing infants. {01}{18}{150} Also, sulfonamides may cause hemolytic anemia in glucose-6-phosphate dehydrogenase (G6PD)–deficient infants.

{26}

Trimethoprim—Trimethoprim is distributed into breast milk. {01} Trimethoprim may interfere with folic acid metabolism in nursing infants.

Pediatrics

Sulfonamides compete for bilirubin binding sites on plasma albumin, increasing the risk of kernicterus in the newborn. Also, because the acetyltransferase system is not fully developed in the newborn, increased blood concentrations of the free sulfonamide can further increase the risk of kernicterus. {26}{38}

Sulfadiazine and trimethoprim:

Sulfadiazine and trimethoprim combination is not recommended in premature infants and neonates up to 12 weeks of age.

{150}

Sulfamethoxazole and trimethoprim:

Although sulfamethoxazole and trimethoprim combination is indicated in the treatment of acute otitis media in children, it is not indicated for prophylaxis or prolonged therapy. {03}

Except as concurrent adjunctive therapy with pyrimethamine in the treatment of congenital toxoplasmosis or for the prophylaxis of Pneumocystis carinii pneumonia (PCP) in infants 4 weeks of age or over, the use of sulfamethoxazole and trimethoprim combination is contraindicated in infants up to 2 months of age since sulfonamides may cause kernicterus in neonates.

{18}{56}

Geriatrics

Elderly patients may be at increased risk of severe side/adverse effects. Severe skin reactions, generalized bone marrow depression, and decreased platelet count (with or without purpura) are the most frequently reported severe side/adverse effects in the elderly. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients who are receiving diuretics, primarily thiazides, concurrently with sulfonamide and trimethoprim combinations.

{01}{18}{27}{150}

Pharmacogenetics
Sulfonamides are metabolized primarily by acetylation. {41} Patients can be divided into 2 groups, slow and quick acetylators. Slow acetylators own a higher incidence of severe sulfonamide reactions, although a slow acetylator phenotype is not thought to be the sole reason for sulfonamide toxicity. {41}{42}{43}{44}{83} The incidence of the slow acetylator phenotype is approximately 50% in North American blacks and whites.

{41}{42}{45}{83} Approximately 30% of the Hispanic population {43} and 10% of the Asian population {42} are slow acetylators. Also, acquired immunodeficiency syndrome (AIDS) patients with acute illness, but not AIDS patients who are stable or human immunodeficiency virus (HIV)-infected patients without AIDS, own an increased incidence of slow acetylation. {43}

Dental

The leukopenic and thrombocytopenic effects of sulfonamides may result in an increased incidence of certain microbial infections, delayed healing, and gingival bleeding.

If leukopenia or thrombocytopenia occurs, dental work should be deferred until blood counts own returned to normal. Patients should be instructed in proper oral hygiene, including caution in use of regular toothbrushes, dental floss, and toothpicks.

Drug interactions and/or related problems
The following drug interactions and/or related problems own been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (»=major clinical significance):

Note:Combinations containing any of the following medications, depending on the quantity present, may also interact with this medication.

» Anticoagulants, coumarin- or indandione-derivative or {01}{47}{124}{125}{150}{168}{169}{170}{171}
» Anticonvulsants, hydantoin or {01}{47}{122}{150}{168}{169}{170}{171}
» Antidiabetic agents, oral {47}{120}{121}{150}{168}{170}{171}(these medications may be displaced from protein binding sites and/or their metabolism may be inhibited by some sulfonamides, resulting in increased or prolonged effects and/or toxicity; dosage adjustments may be necessary during and after sulfonamide therapy)

Atovaquone {149}(concurrent istration of sulfamethoxazole and trimethoprim combination with atovaquone suspension resulted in an 8 and 17% decrease in the steady-state serum concentration of sulfamethoxazole and trimethoprim, respectively; this effect is thought to be minor and is not expected to produce clinically significant events)

Bone marrow depressants (See Appendix II )(concurrent use of bone marrow depressants with sulfonamides may increase the leukopenic and/or thrombocytopenic effects; if concurrent use is required, shut observation for myelotoxic effects should be considered)

Contraceptives, estrogen-containing, oral {29}(concurrent long-term use of sulfonamides may result in reduced contraceptive reliability and increased incidence of breakthrough bleeding)

Cyclosporine {47}{48}{49}{50}{168}(concurrent use with sulfonamides may increase the metabolism of cyclosporine, resulting in decreased plasma concentrations and potential transplant rejection; there may also be additive nephrotoxicity; plasma cyclosporine concentrations and renal function should be monitored)

Dapsone {35}(concurrent use with trimethoprim will generally increase the plasma concentrations of both dapsone and trimethoprim, possibly due to an inhibition in dapsone metabolism, and/or competition for renal secretion between the 2 medications; increased serum dapsone concentrations may increase the number and severity of side effects, especially methemoglobinemia)

» Digoxin {168}(concurrent use with trimethoprim and sulfamethoxazole may increase the serum concentration of digoxin; serum digoxin levels should be monitored)

Folate antagonists, other (See Appendix II ) {150}(concurrent use with trimethoprim or use of trimethoprim between courses of other folic acid antagonists is not recommended because of the possibility of megaloblastic anemia)

» Hemolytics, other (See Appendix II )(concurrent use with sulfonamides may increase the potential for toxic side effects)

» Hepatotoxic medications, other (See Appendix II )(concurrent use with sulfonamides may result in an increased incidence of hepatotoxicity; patients, especially those on prolonged istration or those with a history of liver disease, should be carefully monitored)

Lamivudine (3TC)(in one little study, sulfamethoxazole and trimethoprim combination was found to decrease significantly the clearance, steady-state volume of distribution, and elimination half-life of lamivudine {36}; trimethoprim was also found to decrease the renal clearance of lamivudine by approximately 59% in an isolated perfused rat kidney {67})

» Methenamine {37}{38}(in acid urine, methenamine breaks below into formaldehyde, which may form an insoluble precipitate with certain sulfonamides and may also increase the harm of crystalluria; concurrent use is not recommended)

» Methotrexate or {01}{38}{51}{123}{150}{168}{169}{170}{171}
Phenylbutazone or {37}{38}{150}
Sulfinpyrazone {18}{38}{150}(the effect of methotrexate may be potentiated during concurrent use with sulfonamides because of displacement from plasma protein binding sites; phenylbutazone and sulfinpyrazone may displace sulfonamides from plasma protein-binding sites, increasing sulfonamide concentrations)

Procainamide {31}{32}(concurrent use with trimethoprim may increase the plasma concentration of both procainamide and its metabolite, N-acetylprocainamide [NAPA], by decreasing their renal clearance)

Rifampin {30}{38}(concurrent use may significantly increase the elimination and shorten the elimination half-life of trimethoprim)

Thiazide diuretics {01}(there has been an increased incidence of thrombocytopenia with purpura in elderly patients who received sulfamethoxazole and trimethoprim combination with thiazide diuretics)

Tricyclic antidepressants(efficacy of tricyclic antidepressants may be decreased)

Laboratory worth alterations
The following own been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (»=major clinical significance):

With diagnostic test results
Benedict»s test {37}{52}(sulfonamides may produce a false-positive Benedict»s test for urine glucose )

Creatinine determinations {01}{18}{168}(trimethoprim may interfere with the Jaffé alkaline picrate assay for creatinine, resulting in creatinine values that are approximately 10% higher than actual values)

Methotrexate assays, serum {01}{18}{168}{169}(trimethoprim may interfere with serum methotrexate assays if methotrexate is measured by the competitive binding protein technique [CBPA] using a bacterial dihydrofolate reductase as the binding protein; no interference occurs if methotrexate is measured by radioimmunoassay [RIA])

Sulfosalicylic acid test {37}{52}(sulfonamides may produce a false-positive sulfosalicylic acid test for urine protein)

Urine urobilinogen test strip (e.g., Urobilistix) {37}{52}(sulfonamides may interfere with the Urobilistix test for urinary urobilinogen )

With physiology/laboratory test values
Alanine aminotransferase (ALT [SGPT]) values, serum and
Aspartate aminotransferase (AST [SGOT]) values, serum and
Bilirubin, serum(concentrations may be increased {01}{18}{66}{150})

Blood urea nitrogen (BUN) and
Creatinine, serum(concentrations may be increased {01}{37}{49}{66})

Glucose, blood(concentrations may be decreased, resulting in hypoglycemia on rare occasions {65})

Potassium, serum(concentrations may be increased; this generally occurs with higher doses, such as for the treatment of Pneumocystis carinii pneumonia, but may also happen at regular doses {76}{77}{78}{79}{80}{81})

Medical considerations/Contraindications
The medical considerations/contraindications included own been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (»=major clinical significance).

Except under special circumstances, this medication should not be used when the following medical problem exists:
» Allergy to sulfonamides, furosemide, thiazide diuretics, sulfonylureas, carbonic anhydrase inhibitors, sulfites, or trimethoprim {01}{18}
Risk-benefit should be considered when the following medical problems exist
» Blood dyscrasias or
» Megaloblastic anemia due to folate deficiency {01}{24}{27}{168}{169}{170}{171}(trimethoprim may cause folic acid deficiency; sulfonamides and trimethoprim may cause blood dyscrasias)

» Glucose-6-phosphate dehydrogenase (G6PD) deficiency {01}{37}{116}{117}{150}{168}{169}{170}{171}(hemolysis may rarely occur; frequency may be dose-related)

» Hepatic function impairment {01}{21}{150}{168}{169}{170}{171}(sulfonamides and trimethoprim are metabolized in the liver; delayed metabolism may increase the risk of toxicity; also, sulfonamides may cause fulminant hepatic necrosis)

» Porphyria {26}{28}(sulfonamides may precipitate an acute attack of porphyria)

» Renal function impairment {01}{21}{27}{150}{168}{169}{170}{171}(sulfonamides and trimethoprim are renally excreted; delayed elimination may increase the risk of toxicity; sulfonamides may cause tubular necrosis or interstitial nephritis)

Patient monitoring
The following may be especially significant in patient monitoring (other tests may be warranted in some patients, depending on condition; »=major clinical significance):

Finish blood counts (CBCs) {01}{27}{150}{168}{169}{170}{171}(may be required prior to and monthly during treatment to detect blood dyscrasias in patients on prolonged therapy; therapy should be discontinued if a significant decrease in the count of any formed blood elements occurs)

Urinalyses {01}{27}{150}{168}{169}{170}{171}(may be required prior to and periodically during treatment to detect crystalluria and/or urinary calculi formation in patients on long-term or high-dose therapy and in patients with impaired renal function)

Side/Adverse Effects

Note:Fatalities own occurred, although rarely, due to severe reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias.

Therapy should be discontinued at the first appearance of skin rash or any serious side/adverse effects or if signs of folic acid deficiency happen. {01}{18}{168}{169}{170}{171}
Patients infected with human immunodeficiency virus (HIV) own a greater incidence of side/adverse effects, especially rash, fever, and leukopenia, than do non-HIV–infected patients. {01}{85}{86}{168}{169}{170}{171} On rare occasions, adverse reactions may become extremely severe or life-threatening.

{85}{86}{87}{88} Adverse effects may happen in up to 65% of acquired immunodeficiency syndrome (AIDS) patients {66}{84}, with 24 to 57% having such severe toxicity that therapy has to be discontinued. {66} Sulfamethoxazole and trimethoprim combination desensitization in HIV-infected patients has been successful in some patients, who own then been capable to tolerate regular dosing for the prophylaxis of Pneumocystis carinii pneumonia (see Selected Bibliography).

{89}{90}{91}{92}{93}{166}
The multiorgan toxicity of sulfonamides is thought to be the result of the way sulfonamides are metabolized in certain patients. It is probably due to the inability of the body to detoxify reactive metabolites. Sulfonamides are metabolized primarily by acetylation. {41}{83}{135} Patients can be divided into slow and quick acetylators.

What is drug allergy test

Slow acetylation of sulfonamides makes more of the medication available for metabolism by the oxidative pathways of the cytochrome P-450 system. {44}{45}{83} These pathways produce reactive toxic metabolites, such as hydroxylamine and nitroso compounds. {43}{44}{45}{135} The metabolites are normally detoxified by scavengers, such as glutathione. However, some populations, such as HIV-infected patients, own low concentrations of glutathione and these metabolites accumulate, producing toxicity.

{43}{46}{83}{135} Patients who are slow acetylators own a higher incidence of sulfonamide hypersensitivity reactions {41}{42}{43}{44}, although severe toxicity has also been seen in quick acetylators. {41} Acetylation status alone cannot fully explain sulfonamide toxicity {45}{83} since approximately 50% of North American blacks and whites are slow acetylators and severe reactions happen in less than 1% of patients treated with sulfonamides. {45} However, decreased acetylation may increase the quantity of sulfonamide metabolized to toxic metabolites.

{45}{135}
Sulfonamides own been associated with crystalluria in the past; however, the risk is little with current sulfonamides and the doses used. Acetylated sulfadiazine has the least solubility, followed by sulfadiazine, acetylated sulfamethoxazole, and sulfamethoxazole. {152} Solubility also varies with pH and dose. The risk of crystalluria is high with sulfadiazine at a combined dose of 6 grams a day (4920 mg of sulfadiazine and 1080 mg of trimethoprim); however, this is 6 times the recommended daily dose.

{152}

The following side/adverse effects own been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent

Hypersensitivity (fever; itching; skin rash){01}{18}{37}{66}

photosensitivity (increased sensitivity of skin to sunlight){01}{18}{37}

Incidence less frequent

Blood dyscrasias (fever and sore throat; pale skin; unusual bleeding or bruising; unusual tiredness or weakness){01}{18}{23}{59}{66}{133}{134}{150}{168}{169}{170}{171}

cholestatic hepatitis (yellow eyes or skin ){01}{68}{69}{70}{71}{129}{130}{150}{168}{169}{170}{171}

pancreatitis (back or stomach pain, severe; quick heart beat; fever; nausea or vomiting; swelling of the stomach){168}{169}{170}{171}

Stevens-Johnson syndrome (aching joints and muscles; redness, blistering, peeling, or loosening of skin; unusual tiredness or weakness){01}{18}{23}{37}{150}{168}{169}{170}{171}

toxic epidermal necrolysis ( difficulty in swallowing; redness, blistering, peeling, or loosening of skin){01}{18}{23}{37}{150}{168}{169}{170}{171}

Incidence rare

Aseptic meningitis (confusion; drowsiness; general feeling of illness; severe headache; nausea; stiff neck and/or back){01}{33}{34}{72}{73}{74}{75}{131}{132}{168}{169}{170}{171}

central nervous system (CNS) toxicity (anxiety; hallucinations; mental depression; nervousness; seizures (convulsions)){01}{126}{127}{128}{150}{168}{169}{170}{171}

Clostridium difficile colitis ( severe abdominal or stomach cramps and pain; abdominal tenderness ; watery and severe diarrhea, which may also be bloody; fever)—may happen up to several weeks after discontinuation of medication{01}{82}{136}

crystalluria or hematuria (blood in urine ; lower back pain; pain or burning while urinating){01}{152}

goiter or thyroid function disturbance ( swelling of front part of neck){01}{37}

interstitial nephritis or tubular necrosis (greatly increased or decreased frequency of urination or quantity of urine; increased thirst; loss of appetite ; nausea; vomiting){01}{37}{150}{168}{169}{170}{171}

methemoglobinemia (bluish fingernails, lips, or skin; hard breathing; pale skin; sore throat and fever; unusual bleeding or bruising; unusual tiredness or weakness){01}{37}{168}{169}{170}{171}

rhabdomyolysis ( fatigue; muscle pain; muscle weakness)—has been reported mainly in AIDS patients

thrombophlebitis (pain at site of injection){01}{37}

Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent

CNS effects (dizziness; headache; ringing in the ears; tiredness){01}{23}{37}{150}

gastrointestinal disturbances (abdominal pain ; diarrhea; loss of appetite; nausea or vomiting){01}{18}{23}{37}{66}{150}

glossitis or stomatitis (mouth sores; swelling of the tongue){168}{169}{170}{171}

Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Sulfonamides and Trimethoprim (Systemic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
» Conditions affecting use, especially:
Allergy to sulfonamides, furosemide, thiazide diuretics, sulfonylureas, carbonic anhydrase inhibitors, sulfites, or trimethoprim

Pregnancy—Sulfonamides and trimethoprim cross the placenta; trimethoprim may interfere with folic acid metabolism; use is not recommended at term since sulfonamides may cause jaundice, hemolytic anemia, and kernicterus in neonates

Breast-feeding—Sulfonamides and trimethoprim are distributed into breast milk; sulfonamides may cause kernicterus in nursing infants; trimethoprim may interfere with folic acid metabolism

Use in children—Sulfadiazine and trimethoprim combination is contraindicated in infants up to 3 months of age and sulfamethoxazole and trimethoprim combination is contraindicated in infants up to 2 months of age for most indications since sulfonamides may cause kernicterus in neonates; however, sulfamethoxazole and trimethoprim combination is indicated in every infants born to human immunodeficiency virus (HIV)–infected mothers, starting at 4 to 6 weeks

Use in the elderly—Elderly patients, especially those also taking diuretics, may be at increased risk of severe side/adverse effects
Other medications, especially coumarin- or indandione-derivative anticoagulants, hydantoin anticonvulsants, oral antidiabetic agents, other hemolytics, other hepatotoxic medications, methenamine, or methotrexate
Other medical problems, especially blood dyscrasias, G6PD deficiency, hepatic function impairment, megaloblastic anemia due to folic acid deficiency, porphyria, and renal function impairment

Proper use of this medication
» Not giving sulfadiazine and trimethoprim combination to infants under 3 months of age, or sulfamethoxazole and trimethoprim combination to infants under 2 months of age, except under special circumstances

» Maintaining adequate fluid intake

Proper istration technique for oral liquids

» Compliance with full course of therapy

» Importance of not missing doses and taking at evenly spaced times

» Proper dosing
Taking as soon as possible; not taking if almost time for next dose; not doubling doses

» Proper storage

Precautions while using this medication
» Regular visits to physician to check blood counts

Checking with physician if no improvement within a few days

Caution in use of regular toothbrushes, dental floss, and toothpicks; deferring dental work until blood counts own returned to normal; checking with physician or dentist concerning proper oral hygiene

» Possible skin photosensitivity

» Caution if dizziness occurs

Side/adverse effects
Severe skin problems and blood problems may be more likely to happen in elderly patients who are taking sulfamethoxazole and trimethoprim combination, especially if diuretics are being taken concurrently

Signs of potential side effects, especially hypersensitivity, photosensitivity, blood dyscrasias, cholestatic hepatitis, pancreatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, aseptic meningitis, central nervous system toxicity, Clostridium difficile colitis, crystalluria, hematuria, goiter, thyroid function disturbance, interstitial nephritis, tubular necrosis, methemoglobinemia, rhabdomyolysis and thrombophlebitis

General Dosing Information
Fluid intake should be sufficient to maintain urine output of at least 1200 mL per day in adults.

{05}{18}

Adults with renal function impairment require a reduction in dose in sulfonamide and trimethoprim combinations as follows: {01}{150}

SULFADIAZINE AND TRIMETHOPRIM

Summary of Differences
Indications: Sulfadiazine and trimethoprim combination is recommended for use only in the treatment of urinary tract infections.

Pharmacology/pharmacokinetics: Compared to sulfamethoxazole, sulfadiazine achieves higher concentrations in the bile and cerebrospinal fluid, is metabolized to a lesser extent, and a higher percentage of athletic medication is eliminated in the urine.

{14}{23}{37}{151}{152}{155}{156}{165}

Additional Dosing Information
The usual length of therapy when treating an uncomplicated lower urinary tract infection with sulfadiazine and trimethoprim combination is three {157}{159}{160} to five {158} days in women and seven to ten days in men {64}. Therapy should be continued for fourteen days or more in upper urinary tract infections. {64}

Oral Dosage Forms

SULFADIAZINE AND TRIMETHOPRIM ORAL SUSPENSION

Usual adult and adolescent dose
Antibacterial
Oral, 820 mg of sulfadiazine and 180 mg of trimethoprim once a day.

{150}

Usual pediatric dose
Antibacterial
Infants up to 3 months of age: Use is not recommended. {150}

Children 3 months to 12 years of age: Oral, 7 mg of sulfadiazine and 1.5 mg of trimethoprim per kg of body weight every twelve hours. {150}

Children over 12 years of age: See Usual adult and adolescent dose.{150}

Strength(s) generally available
U.S.—
Not commercially available.

Canada—

205 mg of sulfadiazine and 45 mg of trimethoprim per 5 mL (Rx) [Coptin]

Packaging and storage:
Store under 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer.

Auxiliary labeling:
• Shake well.
• Take with a full glass of water.
• May cause dizziness.
• Avoid too much sun or use of sunlamp.
• Continue medicine for full time of treatment.

Note:When dispensing, include a calibrated liquid-measuring device.

SULFADIAZINE AND TRIMETHOPRIM TABLETS

Usual adult and adolescent dose
See Sulfadiazine and Trimethoprim Oral Suspension .

{150}

Usual pediatric dose
See Sulfadiazine and Trimethoprim Oral Suspension . {150}

Strength(s) generally available
U.S.—
Not commercially available.

Canada—

410 mg of sulfadiazine and 90 mg of trimethoprim (Rx) [Coptin]

820 mg of sulfadiazine and 180 mg of trimethoprim (Rx) [Coptin 1]

Packaging and storage:
Store under 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer.

Auxiliary labeling:
• Take with a full glass of water.
• May cause dizziness.
• Avoid too much sun or use of sunlamp.
• Continue medicine for full time of treatment.

SULFAMETHOXAZOLE AND TRIMETHOPRIM

Summary of Differences
Pharmacology/pharmacokinetics: Sulfamethoxazole is more soluble in urine than is sulfadiazine.

{152}

Additional Dosing Information
Therapy should be continued for at least ten to fourteen days in acute exacerbations of chronic bronchitis {05}; as single-dose therapy or for three to five {119} days in urinary tract infections {101}{140}{141}{143}{144}; for five {05} to seven {119} days in shigellosis; for ten days in acute otitis media in children {05}; for five days in travelers diarrhea {05}; and for fourteen to twenty-one days in Pneumocystis carinii pneumonia {05}.

Sulfamethoxazole and trimethoprim combination may also be given for one or two days or as single-dose therapy for lower urinary tract infections. Therapy should be continued for fourteen days or more in upper urinary tract infections. {64}

Oral Dosage Forms

Note:Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.

SULFAMETHOXAZOLE AND TRIMETHOPRIM ORAL SUSPENSION USP

Usual adult and adolescent dose
Antibacterial (systemic)
Oral, 800 mg of sulfamethoxazole and 160 mg of trimethoprim every twelve hours.

{03}{05}

Antiprotozoal

Pneumocystis carinii pneumonia {03}:

Treatment—
Oral, 18.75 to 25 mg of sulfamethoxazole and 3.75 to 5 mg of trimethoprim per kg of body weight every six hours for fourteen to twenty-one days {03}{05}{168}{169}{170}{171}.

Prophylaxis1
Oral, 800 mg of sulfamethoxazole and 160 mg of trimethoprim once a day. {05}{94}{97}{98}{99}{168}{170}

Acceptable alternative dosing schedules include—
Oral, 800 mg of sulfamethoxazole and 160 mg of trimethoprim three times a week (e.g., Monday, Wednesday, Friday) {55}{62}{63}{94}.

Oral, 400 mg of sulfamethoxazole and 80 mg of trimethoprim once a day {94}{96}{99}.

[Toxoplasmosis (prophylaxis)]1:
Oral, 800 mg of sulfamethoxazole and 160 mg of trimethoprim once a day.

{94}

Acceptable alternative dosing schedules include—
Oral, 800 mg of sulfamethoxazole and 160 mg of trimethoprim three times a week (e.g., Monday, Wednesday, Friday) {94}.

Oral, 400 mg of sulfamethoxazole and 80 mg of trimethoprim once a day. {94}

[ HIV-related infection in Africa (prophylaxis)]1
Oral, 800 mg of sulfamethoxazole and 160 mg of trimethoprim once a day{172}{173}{174}.

Usual pediatric dose
Antibacterial (systemic)

Infants up to 2 months of age:
Use is not recommended since sulfonamides may cause kernicterus in neonates.

{03}{168}{169}{170}{171}

Infants 2 months of age and over:
Infants and children up to 40 kg of body weight—Oral, 20{168}{170} to 30 mg of sulfamethoxazole and 4 {168}{170}to 6 mg of trimethoprim per kg of body weight every twelve hours. {03}{58}

Children 40 kg of body weight and over—See Usual adult and adolescent dose.

Antiprotozoal

  • Song KH, Jung SI, Lee S, et al.

    Inoculum effect of methicillin-susceptible Staphylococcus aureus against broad-spectrum beta-lactam antibiotics. Eur J Clin Microbiol Infect Dis. 2019;38(1):67-74. [PMID:30269181]

    Comment: Among 302 MSSA isolates in this South Korean study representing hospital isolates, 254 (84.1%) were positive for blaZ; types A, B, C and D were 13.6%, 26.8%, 43.4% and 0.3%, respectively. Mean HI MICs of every tested antibiotics were significantly increased and increases in HI MIC of piperacillin/tazobactam (HI, 48.14 ± 4.08 vs. SI, 2.04 ± 0.08 mg/L, p <  0.001) and ampicillin/sulbactam (HI, 24.15 ± 1.27 vs. SI, 2.79 ± 0.11 mg/L, p <  0.001) were most prominent.

    No MSSA isolates exhibited meropenem InE, and few isolates exhibited cefepime (0.3%) and ceftriaxone (2.3%) InE, whereas 43.0% and 65.9% of MSSA isolates exhibited piperacillin/tazobactam and ampicillin/sulbactam InE, respectively. About 93% of type C blaZ versus 45% of non-type C exhibited ampicillin/sulbactam InE (p <  0.001) and 88% of type C blaZ versus 9% of non-type C exhibited piperacillin/tazobactam InE (p <  0.001). A large proportion of MSSA clinical isolates, especially those positive for type C blaZ, showed marked ampicillin/sulbactam InE and piperacillin/tazobactam.

  • Rieg S, von Cube M, Kaasch A, et al. Investigating the impact of early valve surgery on survival in Staphylococcus aureus infective endocarditis using a marginal structural model approach — results of a large prospectively evaluated cohort.

    Clin Infect Dis. 2018. [PMID:30346527]

    Comment: Although early valve surgery advocated by numerous, this series did not discover significant benefit.

  • Carr DR, Stiefel U, Bonomo RA, et al. A Comparison of Cefazolin Versus Ceftriaxone for the Treatment of Methicillin-Susceptible Staphylococcus aureus Bacteremia in a Tertiary Care VA Medical Middle. Open Forum Infect Dis. 2018;5(5):ofy089. [PMID:30568987]
  • Nambiar K, Seifert H, Rieg S, et al. Survival following Staphylococcus aureus bloodstream infection: A prospective multinational cohort study assessing the impact of put of care.

    J Infect. 2018;77(6):516-525. [PMID:30179645]

    Comment: Among diverse hospitals, mortality rates among the pooled 1851 patients with a median age of 66 years (64% male) were analyzed. Crude 90-day mortality differed significantly between hospitals (range 23-39%) which authors attributed to numerous factors.

  • Holland TL, Raad I, Boucher HW, et al. Effect of Algorithm-Based Therapy vs Usual Care on Clinical Success and Serious Adverse Events in Patients with Staphylococcal Bacteremia: A Randomized Clinical Trial.

    JAMA. 2018;320(12):1249-1258. [PMID:30264119]

    Comment: Randomized trial of 509 adults with staphylococcal bacteremia, use of an algorithm compared with usual care resulted in a clinical success rate of 82.0% vs 81.5%, respectively—showing little difference and similar serious adverse events occurred in 32.5% vs 28.3% of patients, a difference that was not statistically significant but with wide confidence intervals. The trial used 14 +/- 2 d for short course vs. 28-42 days for complicated. Trial suggests that staphylococcal bacteremia can be treated by the algorithm if diagnostic and therapeutic recommendations are followed.

    An exciting sidebar is in the uncomplicated, short-course group, the failure rate was 25-30%.

  • Daum RS, Miller LG, Immergluck L, et al. A Placebo-Controlled Trial of Antibiotics for Smaller Skin Abscesses. N Engl J Med. 2017;376(26):2545-2555. [PMID:28657870]
  • Talan DA, Mower WR, Krishnadasan A, et al. Trimethoprim-Sulfamethoxazole versus Placebo for Uncomplicated Skin Abscess. N Engl J Med. 2016;374(9):823-32. [PMID:26962903]

    Comment: Rather surprising results from this study that is in contrast to the «no antibiotic needed» dogma for uncomplicated, drained S aureus abscesses.

    Study suggested higher cure rates in 507 of 630 participants (80.5%) in the trimethoprim-sulfamethoxazole group versus 454 of 617 participants (73.6%) in the placebo group (difference, 6.9 percentage points; 95% confidence interval [CI], 2.1 to 11.7; P=0.005).

  • Berbari EF, Kanj SS, Kowalski TJ, et al. Executive Summary: 2015 Infectious Diseases Society of America (IDSA) Clinical Practice Guidelines for the Diagnosis and Treatment of Native Vertebral Osteomyelitis in Adults. Clin Infect Dis. 2015;61(6):859-63. [PMID:26316526]

    Comment: Guidance document suggesting 6 wks of parenteral or highly bioavailable oral therapy for native (no hardware) vertebral osteomyelitis.

    First line choices for MSSA, recs include nafcillin, oxacillin, cefazolin or ceftriaxone. For MRSA, vancomycin or daptomycin.

  • Walters MS, Eggers P, Albrecht V, et al. Vancomycin-Resistant Staphylococcus aureus — Delaware, 2015. MMWR Morb Mortal Wkly Rep. 2015;64(37):1056. [PMID:26402026]

    Comment: Reasons for limited development of VRSA is unclear (compared to enterococci); however, only 14 isolates described since 2001. Final four own been from the state of Delaware.

  • Miller LG, Daum RS, Creech CB, et al. Clindamycin versus trimethoprim-sulfamethoxazole for uncomplicated skin infections.

    N Engl J Med. 2015;372(12):1093-103. [PMID:25785967]

    Comment: As TMP/SMX often thought of as a better staph than strep agent, this study found no diverse between clindamycin or TMP/SMX in those with either abscess, cellulitis or mixed infection. This suggests that fretting about choices if more celllulitic vs. abscess scenarios is not necessary for those with mild-moderate infections.

  • Paul M, Bishara J, Yahav D, et al. Trimethoprim-sulfamethoxazole versus vancomycin for severe infections caused by meticillin resistant Staphylococcus aureus: randomised controlled trial. BMJ. 2015;350:h2219.

    [PMID:25977146]

    Comment: For those with severe infections including bacteremia especially, TMP/SMX did not acheive non-inferiority compared to vancomycin. Multivariable logistic regression had trimethoprim-sulfamethoxazole significantly associated with treatment failure (adjusted odds ratio 2.00, 1.09 to 3.65).

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    The 30 day mortality rate was 32/252 (13%), with no significant difference between arms. Among patients with bacteraemia, 14/41 (34%) treated with trimethoprim-sulfamethoxazole and 9/50 (18%) with vancomycin died (risk ratio 1.90, 0.92 to 3.93).

  • del Río A, Gasch O, Moreno A, et al. Efficacy and safety of fosfomycin plus imipenem as save therapy for complicated bacteremia and endocarditis due to methicillin-resistant Staphylococcus aureus: a multicenter clinical trial. Clin Infect Dis. 2014;59(8):1105-12. [PMID:25048851]

    Comment: Available in some European and other countries, this little study examined S aureus bacteremia or endocarditis and found that fosfomycin [2g IV q 6] + imipenem appeared to be helpful in those failing regimens including vancomcyin, daptomycin and others.

    Success rate was 69% of the 16 patients.

  • Kaasch AJ, Barlow G, Edgeworth JD, et al. Staphylococcus aureus bloodstream infection: a pooled analysis of five prospective, observational studies. J Infect. 2014;68(3):242-51. [PMID:24247070]

    Comment: Five cohorts of S. aureus bacteremia with adjusted HR mortality in this group of 3346 with 30d mortality = 21%, 90d mortality = 29%.

  • Pallin DJ, Binder WD, Allen MB, et al. Clinical trial: comparative effectiveness of cephalexin plus trimethoprim-sulfamethoxazole versus cephalexin alone for treatment of uncomplicated cellulitis: a randomized controlled trial.

    Clin Infect Dis. 2013;56(12):1754-62. [PMID:23457080]

    Comment: Interestingly this trial did not propose that adding an agent with activity against CA-MRSA (TMP/SMX) did not substantially improve outcomes [82% cephalexin alone, 85% combination]. This suggests that MRSA is not a common driver of cellulitis in the absence of purulence.

  • Wunderink RG, Niederman MS, Kollef MH, et al. Linezolid in methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a randomized, controlled study.

    Clin Infect Dis. 2012;54(5):621-9. [PMID:22247123]

    Comment: Fairly large trial in a hard to study condition. RCT examined linezolid (600 mg every 12 hours) or vancomycin (15 mg/kg every 12 hours) x 7-14d. Enrolled pts numbered 1184, 448 (linezolid, n = 224; vancomycin, n = 224) were included in the mITT and 348 (linezolid, n = 172; vancomycin, n = 176) in the PP population. In the PP population, 95 (57.6%) of 165 linezolid-treated patients and 81 (46.6%) of 174 vancomycin-treated patients achieved clinical success at EOS (95% confidence interval for difference, 0.5%-21.6%; P = .042). Howvever, all-cause 60-day mortality was similar (linezolid, 15.7%; vancomycin, 17.0%), as was incidence of adverse events.

    Nephrotoxicity occurred more frequently with vancomycin (18.2%; linezolid, 8.4%). This study suggests that the PK/PD elements favoring linezolid may in fact own clinical efficacy favorable over vancomycin but the larger 60d picture is not telling. For the extremely ill with potential for added complications such as renal failure, linezolid may be the better option.

  • Vos FJ, Kullberg BJ, Sturm PD, et al. Metastatic infectious disease and clinical outcome in Staphylococcus aureus and Streptococcus species bacteremia. Medicine (Baltimore). 2012;91(2):86-94. [PMID:22391470]

    Comment: Study of 115 patients with staph or strep bacteremia using FDG-PET/CT technology looking for metastatic infections found foci in 84 of 115 (73%) patients: endocarditis (22 cases), endovascular infections (19 cases), pulmonary abscesses (16 cases), and spondylodiscitis (11 cases) were diagnosed most frequently.

    Signs or symptoms directing a diagnostic work-up were only present in 41%, suggesting that additional studies may be helpful even in absence of specific findings: for example in this study PET was the first to detect problems in 30%.

  • Thwaites GE, Edgeworth JD, Gkrania-Klotsas E, et al. Clinical management of Staphylococcus aureus bacteraemia. Lancet Infect Dis. 2011;11(3):208-22. [PMID:21371655]

    Comment: Important to note that only 16 studies with < 1500 patients in RCTs form basis for guidance in this hard infection.

    Authors rightly point out that much guideline recommendations are based on observational or limited case studies. Key questions that remain to be answered in their opinion include: 1) How should SAB be defined?, 2) Is identification and removal of infection focus important? 3) Should every SAB pts own echocardiography? 4) Are glycopeptides equivalent to beta-lactams? 5) Are cephalosporins equivalent to penicillins?, 6) Is teicoplanin as effective as vancomycin? 7) What is the optimum duration of treatment for SAB? 8) Is oral therapy the equivalent to parenteral? 9) Is combination therapy better than monotherapy?

    10) what is the role of linezolid, daptomycin and newer antimicrobials?
    Rating: Important

  • Dhand A, Bayer AS, Pogliano J, et al. Use of antistaphylococcal beta-lactams to increase daptomycin activity in eradicating persistent bacteremia due to methicillin-resistant Staphylococcus aureus: role of enhanced daptomycin binding. Clin Infect Dis. 2011;53(2):158-63. [PMID:21690622]

    Comment: Authors capable to clear persistent bacteremia in 7 pts with combination of daptomycin and oxacillin or nafcillin (2g IV q4h) in seven patients. Mechanism not entirely clear but may be due to enhanced membrane binding of daptomycin in the presence of the beta-lactam.

  • Simor AE.

    Staphylococcal decolonisation: an effective strategy for prevention of infection? Lancet Infect Dis. 2011;11(12):952-62. [PMID:22115070]

    Comment: Best data regarding decolonization efficacy exists in pre-surgical patients and those on dialysis. Efficacy for decreasing CA-MRSA recurrent infections doesn’t yet exist in robust fashion.
    Rating: Important

  • Cosgrove SE, Vigliani GA, Fowler VG, et al. Initial low-dose gentamicin for Staphylococcus aureus bacteremia and endocarditis is nephrotoxic. Clin Infect Dis. 2009;48(6):713-21. [PMID:19207079]

    Comment: Evidence for nephrotoxicity associated with short course synergy dose gentamicin in the treatment of S.

    aureus bacteremia and endocarditis.

  • Figueroa DA, Mangini E, Amodio-Groton M, et al. Safety of high-dose intravenous daptomycin treatment: three-year cumulative experience in a clinical program. Clin Infect Dis. 2009;49(2):177-80. [PMID:19500039]

    Comment: Single middle study evaluating the safety of higher doses of daptomycin.
    Rating: Important

  • Fowler VG, Boucher HW, Corey GR, et al. Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus. N Engl J Med. 2006;355(7):653-65.

    [PMID:16914701]

    Comment: Recent publication demonstrating that daptomycin is not inferior to standard therapy in the treatment of S. aureus bacteremia and right-sided endocarditis.
    Rating: Important

  • Cosgrove SE, Carroll KC, Perl TM. Staphylococcus aureus with reduced susceptibility to vancomycin. Clin Infect Dis. 2004;39(4):539-45. [PMID:15356818]

    Comment: Review of the epidemiology, diagnosis, and management of patients with S. aureus with reduced susceptibility to vancomycin.
    Rating: Important

  • Naimi TS, LeDell KH, Como-Sabetti K, et al. Comparison of community- and health care-associated methicillin-resistant Staphylococcus aureus infection.

    JAMA. 2003;290(22):2976-84. [PMID:14665659]

    Comment: A study that elucidates the clinical and microbiologic differences between healthcare-associated MRSA and community-associated MRSA.
    Rating: Important

  • von Eiff C, Becker K, Machka K, et al. Nasal carriage as a source of Staphylococcus aureus bacteremia. Study Group. N Engl J Med. 2001;344(1):11-6. [PMID:11136954]

    Comment: A German study indicating that S. aureus bacteremia appears to frequently be caused by strains of S. aureus colonizing the patient’s own nasal mucosa.

    An accompanying editorial emphasizes the importance of attempting to eradicate this colonization in order to control nosocomial infections, but highlights the failure of most currently used agents to achieve this goal (N Engl J Med 2001; 344: 55-57)

  • Fowler VG, Li J, Corey GR, et al. Role of echocardiography in evaluation of patients with Staphylococcus aureus bacteremia: experience in 103 patients. J Am Coll Cardiol. 1997;30(4):1072-8. [PMID:9316542]

    Comment: A study demonstrating the presence of endocarditis in 25% of patients with S.

    aureus bacteremia when evaluated with TEE.
    Rating: Important

  • Heldman AW, Hartert TV, Ray SC, et al. Oral antibiotic treatment of right-sided staphylococcal endocarditis in injection drug users: prospective randomized comparison with parenteral therapy. Am J Med. 1996;101(1):68-76. [PMID:8686718]

    Comment: A study comparing standard therapy for right-sided endocarditis to oral ciprofloxacin and rifampin for 4 weeks that demonstrates the efficacy of the oral regimen.

  • DiNubile MJ. Short-course antibiotic therapy for right-sided endocarditis caused by Staphylococcus aureus in injection drug users. Ann Intern Med. 1994;121(11):873-6.

    [PMID:7978701]

    Comment: A review of the option of shorter course antibiotic therapy for right-sided heart infections in injection drug users.

  • Markowitz N, Quinn EL, Saravolatz LD. Trimethoprim-sulfamethoxazole compared with vancomycin for the treatment of Staphylococcus aureus infection. Ann Intern Med. 1992;117(5):390-8. [PMID:1503330]

    Comment: A study of 101 injection drug users with S.

    aureus infection of whom 65% were bacteremic. The success rate for therapy of MRSA infections was equivalent for the TMP-SMX and vancomycin groups, although vancomycin was marginally more successful as a therapy in the non-MRSA group. The authors thus suggests that TMP-SMX may be a viable alternative to vancomycin for MRSA infection in this group of patients. Failures with TMP/SMX were seen only in the group with endocarditis but not those with straight (or supposedly straight) bacteremia.
    Rating: Important

  • Tranter HS. Foodborne staphylococcal illness.

    Lancet. 1990;336(8722):1044-6. [PMID:1977028]

    Comment: A review of GI tract infections caused by ingestion of certain toxin-producing strains of S. aureus.

  • Lee BK, Crossley K, Gerding DN. The association between Staphylococcus aureus bacteremia and bacteriuria. Am J Med. 1978;65(2):303-6. [PMID:686015]

    Comment: The classic paper describing the presence of S.

    What is drug allergy test

    aureus bacteriuria in 27% of patients with S. aureus bacteremia in the absence of obvious renal infection.


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