September ID Update

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 Approvals

  • Benznidazole* for the treatment of pediatric patients 2 to 12 years of age with Chagas disease* (American trypanosomiasis), a parasitic infection caused by Trypanosoma cruzi. Recommended dosage: 5-8 mg/kg/day (divided q12h) x60 days.
  • Vabomere (Meropenem + Vaborbactam)* for the treatment of patients ≥18 years of age with complicated urinary tract infection including pyelonephritis caused by E. coli, K. pneumoniae, and E. cloacae. Meropenem is a carbapenem and Vaborbactam is a cyclic boronic acid beta-lactamase inhibitor. Recommended dosage in normal renal function: 4 gm (Meropenem 2 gm/Vaborbactam 2 gm) IV q8h (each dose infused over 3 hr).

Updated Treatment Guidelines

  • The annual report from the Advisory Committee on Immunization Practices (ACIP) regarding the use of influenza* vaccines has been released (MMWR Recomm Rep 2017; 66 [No. RR-2]: 1–20). For the 2017–18 season, inactivated and recombinant influenza vaccine will be available in trivalent and quadrivalent formulations. Live attenuated influenza vaccine is not recommended due to concerns about its effectiveness against (H1N1)pdm09 viruses during the 2013–14 and 2015–16 seasons. No preferential recommendation is made for one vaccine product over another for persons for whom more than one licensed, recommended product is available. The full report is available on the CDC MMWR website.
  • Recommendations from the American Academy of Pediatrics (AAP) for routine use of the seasonal influenza vaccine and antiviral medications for the prevention and treatment of influenza in children have been published online (Pediatrics 2017 Sep 4 [Epub ahead of print]). The AAP recommends that pediatricians offer influenza vaccine to all children 6 months of age and older, as soon as the vaccine becomes available, in order to complete vaccination and provide protection before the flu season starts. The recommendations are available for download on the AAP website.
  • The Guidance for Non-HIV-Specialized Providers Caring for Persons with HIV Displaced by Disasters has been updated. Included are recommendations based on the current standard of care for persons with HIV infection and also specific guidance on management of HIV infection during pregnancy. In addition, the guidance includes an intake form clinicians can use when evaluating a patient with HIV, a collection of web-based resources for information on treatment and prevention of HIV, and a list of temporary regimen substitutions in case of supply shortages. The guidance is available for download on the AIDSinfo website.
  • Updated European guidelines for the management of genital herpes have been published online (Int J STD AIDS 2017 Jan 1 [Epub ahead of print]). The guidelines are available for download on the International Union against Sexually Transmitted Infections (IUSTI) website.
  • Updated guidelines for the diagnosis and empirical treatment of fever of unknown origin in adult neutropenic* patients from the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO) have been published (Ann Hematol 2017 Aug 30 [Epub ahead of print]). These guidelines update the 2003 release and are available for download on the journal website.

Update on Miltefosine

  • CDC is no longer providing Miltefosine* for treatment of free-living amoeba infections (AcanthamoebaBalamuthia, Naegleria). It is commercially available and must be obtained directly from Profounda, Inc. (www.profounda.com).

Practice Pearls

  • With the introduction of meropenem/vaborbactam* there are now five commercially available beta-lactamase inhibitors marketed in combination with a companion antibacterial agent (relebactam is not yet commercially available). Here is a chart of their activities versus the various classes of beta-lactamase enzyme. The letter in parentheses refers to the Ambler beta-lactamase class (the Ambler classification scheme is based on amino acid sequence homology).
TEM/SHV (A) CTX-M (A) KPC (A) MBL (B) AmpC (C) OXA (D)
Clavulanate Yes Yes No No No No
Sulbactam Yes Yes No No No No
Tazobactam Yes Yes No No No No
Avibactam Yes Yes Yes No Yes Yes
Vaborbactam Yes Yes Yes No Yes No
Relebactam Yes Yes Yes No Yes ?

NOTES:

  1. TEM and SHV are common beta-lactamases found in Gram-negative bacteria
  2. The CTX-M family is a type of extended-spectrum beta-lactamase (ESBL)
  3. KPC is Klebsiella pneumoniae carbapenemase
  4. MBL is metallo-beta-lactamase (e.g. IMP, VIM, NDM)
  5. AmpC is the inducible chromosomal beta-lactamase associated with certain Enterobacteriaceae (Serratia, Enterobacter, Aeromonas, Citrobacter, Hafnia, indole-positive Proteus, Morganella, Providencia)
  6. Some OXA enzymes may be inhibited by tazobactam or clavulanate
  7. References: Drugs 77:615, 2017 and Clin Microbiol Rev 23:160, 2010.
  • Inflammatory processes seem to play a role in a variety of psychiatric disorders, and recent data suggest that anti-inflammatory drugs may be useful adjunctive treatment for depression. Could the anti-inflammatory properties of minocycline* be useful in this regard? In a small (n=41), randomized, double-blind, placebo-controlled pilot trial in patients with treatment-resistant major  depressive disorder, minocycline (100 mg qd x2 weeks, then 200 mg qd x10 weeks) was added to existing antidepressant treatment. A large, statistically significant decrease in Hamilton Depression Rating Scale was observed in the minocycline group. Clinical Global Impression score was significantly improved, and other measures showed improvement as well. Minocycline was well tolerated. These preliminary findings require confirmation in larger studies with longer follow-up periods (J Psychopharmacol 2017 Aug 1 [Epub ahead of print]).
  • Oral fosfomycin* is considered a firstline option for uncomplicated cystitis, although it appears to have inferior efficacy compared with other short course regimens. Despite being an “old” drug, our knowledge of its urinary pharmacokinetics is limited. A single 3 gram dose of fosfomycin was administered to 40 healthy females and urine samples were collected for a week. Peak urine concentration was 1982 mcg/mL with considerable intersubject variability (SD 1257). Mean urine Tmax was 7.5 hours, and mean urine half-life was 12.4 hours. High urinary output was correlated with low urine concentrations. It is possible that inadequate drug exposure (resulting from intersubject differences) explains treatment failure in some patients (Clin Microbiol Infect 2017 Aug 31 [Epub ahead of print]).

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]: Cefpodoxime oral suspension
    • [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: None
      • Vaccines: Hepatitis A Virus Vaccine Inactivated (Vaqta), Hepatitis B vaccine recombinant, Yellow Fever vaccine (unavailable)
    • [Shortage recently resolved]: Albendazole tablets, Tetanus and Diphtheria Toxoids Adsorbed
  • 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