July ID Update Second Edition

ID Update is The Sanford Guide’s monthly summary of significant developments in the treatment of infectious diseases. Want to receive ID Update by e-mail? Click here to subscribe. We won’t spam you or share your contact information.

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New Drug Approval

  • Delafloxacin* (Baxdela), the first new fluoroquinolone antibiotic in many years, was approved by the US FDA in late June. It is indicated for the treatment of adults with acute bacterial skin and skin structure infections caused by designated susceptible bacteria, including MRSA. The recommended dosage is 300 mg IV q12h or 450 mg po q12h x5-14 days. Product availability: 450 mg tablets, injection.

Updated Treatment Guidelines

  • Updated clinical practice guidelines for the management of hepatitis B virus infection from the European Association for the Study of the Liver have been published (J Hepatol 67:370, 2017). These guidelines update the 2012 release and are available for download on the EASL website.

Antimicrobial Stewardship

  • We know that antibiotic stewardship programs reduce antibiotic use and hospital costs. According to the results of a 32-study meta-analysis, they also reduce the incidence of infection and colonization with multidrug-resistance gram-negative bacteria, ESBL-producing gram-negative bacteria, and MRSA, as well as the incidence of C. difficile infection, in hospital inpatients. No effect on the incidence of VRE, or fluoroquinolone-resistant and aminoglycoside-resistant gram-negative bacteria, was observed. Stewardship programs are more effective when implemented in hematology-oncology settings and with infection control strategies such as improved hand hygiene (Lancet Infect Dis 2017 June 16 [Epub ahead of print]).

Practice Pearls

  • According to the latest guidelines from the American Academy of Dermatology, systemic antibiotics are not to be used for mild acne vulgaris*. Systemic antibiotics are reasonable for moderate to severe cases, but only in combination with one or more topical agents. Doxycycline and minocycline are more effective than tetracycline, and azithromycin should only be used if a tetracycline is contraindicated. Other systemic drugs should be avoided due to resistance concerns (such as erythromycin) or lack of supportive data (Am Fam Phys 95:740, 2017J Am Acad Dermatol 74:945, 2016).
  • Phenazopyridine, useful for the relief of pain, burning, and discomfort in patients with UTI, is a commonly used OTC drug that is not without toxicity. Adverse effects include gastrointestinal disturbances, discoloration of urine and skin, hepatitis, hemolytic anemia, methemoglobinemia, and acute tubular necrosis. Added to the list of phenazopyridine toxicities is a case report of biopsy-proven acute interstitial nephritis. The patient’s renal function improved after stopping the phenazopyridine, worsened when it was reintroduced, and improved again after drug discontinuation plus a brief tapering course of oral corticosteroids (Ren Fail 36:804, 2014).
  • Pyrazinamide, an excellent sterilizing agent, is the only antituberculous drug with bactericidal activity against M. tuberculosis in acidic environments. The currently recommended dose is 20-25 mg/kg/day. Using proposed therapeutic targets of Cmax >35 μg/mL and/or AUC of >363 μg x hr/mL, recent pharmacokinetic data suggest that this dose may be too low for most patients. Mathematical simulations suggest that a daily dose in the range of 30-40 mg/kg or more is needed to achieve the therapeutic target(s) in most patients (Antimicrob Agents Chemother 61:e02625, 2017).
  • Extracorporeal membrane oxygenation (ECMO) may result in increased extraction of highly lipophilic and protein-bound drugs, increased volume of distribution (Vd), and altered clearance. The best published pharmacokinetic data are in neonates, although the trials were largely conducted in the 1980s and 1990s. The most well-defined effect of ECMO in neonates is increased Vd, resulting in the need for higher initial doses of some drugs. In contrast, limited studies of poor quality suggest that Vd and clearance are typically unchanged in adults and thus, there are very few recommendations for dose adjustments in that patient population (Clin Ther 38:1976, 2016).
  • Syphilis during pregnancy* is the classic situation in which desensitization of a patient with evidence of IgE-mediated penicillin allergy is necessary. Repeated administration of subthreshold doses of penicillin is thought to provide sufficient antigenic determinant to bind IgE on the surface of basophils and mast cells without cross-linking, thus rendering them unresponsive to higher doses. Oral penicillin desensitization protocols are generally preferred, although GI absorption may be variable; parenteral administration offers the advantage of easier dosage control and the ability to quickly interrupt a dose if a reaction occurs. Allergic reactions, mostly mild, occur in at 1/3 or more of patients undergoing penicillin desensitization but are typically managed successfully with medications and a temporary pause of the desensitization protocol. Following desensitization, subsequent penicillin doses must be given without interruption; if enough doses are missed that the drug has been cleared from the system, or if penicillin is needed again in the future, then the desensitization procedure must be repeated (Ann Allergy Asthma Immunol 118:537, 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 antimicrobial shortages
    • [Continue to be in reduced supply]:
      • Aminoglycosides: Amikacin injection, Gentamicin injection, Tobramycin injection
      • Cephalosporins: Cefepime, Cefotaxime injection (unavailable), 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 antibacterials: Clindamycin injection, Erythromycin lactobionate injection (unavailable), Metronidazole injection, Mupirocin calcium 2% cream, Mupirocin calcium 2% nasal ointment (unavailable), Vancomycin injection
      • Antifungal drugs: Fluconazole injection
      • Antiparasitic drugs: Albendazole tablets (unavailable)
      • Vaccines: Hepatitis A Virus Vaccine Inactivated (Vaqta), Hepatitis B vaccine recombinant, Tetanus and Diphtheria Toxoids Adsorbed, Yellow Fever vaccine
    • [Shortage recently resolved]: Rabies vaccine (RabAvert)
  • Antimicrobial drugs newly discontinued: No recent discontinuations
    • Recent 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/DrugShortages

Sanford Guide Digital Feature Highlights

  • Caring for a patient with fever who has just returned from abroad? Our page on Fever in Returning Travelers* can help!
  • Colistin* dosing. Check out our newly updated colistin dosing calculator*. This interactive tool provides dose recommendations in terms of colistin base activity (mg or IU) or colistimethate (mg or IU) using new clinician-friendly creatinine clearance level-based dosing algorithms (Clin Infect Dis 64:565, 2017) as well as current dose recommendations from the European Medicines Agency. Access the calculator from the Colistin page, from Tables and Tools >> Calculators, or using Search Site.