May ID Update

CDC Health Alert Network #401

  • CDC has identified an increase in Shigella* isolates in the US with elevated MIC values (0.12-1 μg/mL) for ciprofloxacin*. These isolates likely have a quinolone resistance gene that may lead to clinically significant reduced susceptibility to fluoroquinolone antibiotics. Current CLSI interpretive criteria categorize isolates with a ciprofloxacin MIC of ≤1 μg/mL as susceptible to ciprofloxacin. This Health Advisory outlines new recommendations for diagnosis, management, and reporting of Shigella with possible reduced susceptibility to ciprofloxacin.

Updated Treatment Guidelines

  • Updated guidelines for the use of antiretroviral agents in pediatric HIV infection* from the HHS Panel on Antiretroviral Therapy and Medical Management of Children Living with HIV are available for download off the AIDSinfo website.
  • Updated guidelines for the management of fever and neutropenia in children with cancer and hematopoietic stem-cell transplantation recipients have been published (J Clin Oncol 2017 May 1 [Epub ahead of print]). These guidelines update the 2012 release and are available for download on the JCO website.
  • The last version of the CDC Guideline for Prevention of Surgical Site Infection was published in 1999. Most recommendations were based on expert opinion. CDC has updated that version using a modified Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach (JAMA Surg 2017 May 3 [Epub ahead of print]). The updated guidelines are available for download on the JAMA Surgery website.

Practice Pearls

  • The currently recommended formulation of amoxicillin-clavulanate* for acute otitis media* (AOM) contains the two components in a 14:1 ratio. The trend in commercially available products has been to increase this ratio to provide improved efficacy of amoxicillin against penicillin-nonsusceptible S. pneumoniae while reducing the dose of clavulanate, thereby reducing the incidence of diarrhea while maintaining activity against H. influenzae and M. catarrhalis. The lowest quantity of clavulanate that will provide effective beta-lactamase inhibition has not been determined. In a small, open-label, nonrandomized study, 40 children (age 6-23 months) were treated with a novel 28:1 product (90 mg/kg/day amoxicillin component x10 days). No difference in protocol-defined diarrhea, diaper dermatitis, or AOM clinical response was observed compared to historical controls receiving the standard 14:1 regimen. 72 children were then treated with the 28:1 product at a reduced dosage (80 mg/kg/day amoxicillin component x10 days); a lower (but not statistically significant) reduction in protocol-defined diarrhea and a significantly lower rate of diaper dermatitis was observed compared to historical controls, again with no apparent reduction in clinical efficacy. Pharmacokinetic findings are also presented. These intriguing results await validation in a larger randomized clinical trial (Antimicrob Agents Chemother 2017 Apr 24 [Epub ahead of print]).
  • For treatment of acute pyelonephritis* the current IDSA recommendation is 5-7 days of a fluoroquinolone (ciprofloxacin or levofloxacin, treatment duration depending on the specific choice) or 14 days of TMP-SMX. In this multicenter, retrospective study, 272 women (≥16 years of age) with pyelonephritis were treated with 7 days of TMP-SMX (n=191) or 7 days of ciprofloxacin (n=81). In an adjusted model, the likelihood of a recurrent UTI within 30 days for the two groups was similar. Fewer women treated with TMP-SMX were bacteremic with E. coli or were hospitalized. These data suggest that for pyelonephritis, 7 days of TMP-SMX may be as effective as 7 days of ciprofloxacin. Clinical validation requires a randomized controlled trial (Am J Med 2017 Feb 16 [Epub ahead of print]).
  • For over 60 years the standard duration of treatment with penicillin for acute streptococcal pharyngitis* has been 10 days. A fascinating investigation into the history of this duration shows that it simply evolved over time in an era much different than today. No therapeutic trials have verified the need for 10 days of penicillin to prevent acute rheumatic fever. The decreasing incidence of rheumatic fever in developed countries, the increasing failure rates for streptococcal eradication with penicillin, and the evidence for equivalent streptococcal eradication rates with short-course regimens (mainly cephalosporins) have failed to alter our faithful devotion to 10 days of penicillin for streptococcal pharyngitis. The practice has the longest lineage of any antimicrobial recommendation in clinical infectious disease and seems to be, as the author puts it, an example of “a more generalized phenomenon in clinical medicine, the fierce inertia of established usage” (Pediatr Infect Dis J 36:507, 2017).
  • Obesity is a common co-morbidity among patient with skin and soft tissue infections (SSTIs). The pharmacokinetics and pharmacodynamics of antibiotics used for the prevention and treatment of SSTIs are altered in obesity, often in a complex manner. A specific question that arises regarding surgical prophylaxis with cefazolin* in obese patients undergoing bariatric surgery or cesarean delivery is the initial dose (and also the need for redose). Surgical prophylaxis guidelines suggest a dose of 3 grams for patients weighing at least 120 kg, but supportive data are limited (Am J Health-Syst Pharm 70:195, 2013). More recent PK/PD data including information about target tissue concentrations, although limited, suggest that a 2 gram prophylactic dose is sufficient, with consideration of redosing if the surgical procedure is unexpectedly prolonged. This is supported by a recent retrospective review of 436 surgical patients weighing at least 100 kg in whom the rate of surgical site infection was similar when either a 2 gram or a 3 gram prophylactic dose was administered (Curr Opin Infect Dis 30:180, 2017).

Drug Shortages (US)

  •  Antimicrobial drugs or vaccines in reduced supply or unavailable due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons:
    • [New on the list]: No new shortages reported since April
    • [Continue to be in reduced supply]:
      • Aminoglycosides: Amikacin injection, Gentamicin injection, Tobramycin injection
      • Cephalosporins: Cefepime, Cefotetan, Cefotaxime, Cefoxitin, Ceftazidime, Ceftriaxone, Cefuroxime injection
      • Fluoroquinolones: Ciprofloxacin oral suspension, Ofloxacin 0.3% ophthalmic solution
      • Penicillins: Amoxicillin/clavulanate 1000 mg/62.5 mg ER tablets, Ampicillin/sulbactam, Oxacillin injection, Penicillin G benzathine, Penicillin G benzathine 900,000 units/Penicillin G procaine 300,000 units (Bicillin C-R 900/300), Penicillin G benzathine/Penicillin G procaine 1.2 million units (Bicillin C-R), Penicillin G procaine injection (unavailable), Piperacillin/tazobactam
      • Other antimicrobials: Clindamycin injection, Erythromycin lactobionate injection, Mupirocin calcium 2% cream, Mupirocin calcium 2% nasal ointment (unavailable), Vancomycin injection
      • Vaccines: Hepatitis A Virus Vaccine Inactivated, Rabies vaccine (RabAvert), Tetanus and Diphtheria Toxoids Adsorbed, Yellow Fever vaccine
    • [Shortage recently resolved]: Ampicillin injection, Meningococcal vaccines (various)
  • Antimicrobial drugs newly discontinued: No recent discontinuations
  • Other discontinuations: MenHibrix (in February 2017), Elvitegravir (Vitekta, in December 2016), Peginterferon alfa-2b (in February 2016; 50 mcg vials still available in limited quantities), Boceprevir (in December 2015), Permethrin 1% topical lotion (in September 2015)
  • For detailed information including estimated resupply dates, see http://www.ashp.org/menu/DrugShortage