November ID Update

Sanford Guide ID Update features current developments in infectious diseases, curated by the Sanford Guide Editorial Board. Links marked with an asterisk (*) provide details to Web Edition subscribers, while all other links are universal. To sign up for ID updates to your inbox, register here.
 

November 2020

 

Sanford Guide Announcements

SARS-CoV-2 / COVID-19

  • Sanford Guide SARS-CoV-2 / COVID-19 material is freely available to all for the course of the pandemic.
  • IgG1 monoclonal antibody. BamlanivimabFDA EUA (11/9/20) for outpatient use in mild to moderate COVID-19 in adolescents (age >12 yrs and wt > 40 kg) and adults who are at risk of progression to severe disease.
  • Guidelines on COVID-19 diagnosis, serology, treatment and management, and infection prevention: IDSA and NIH.
  • A living WHO guideline on drugs for COVID-19 (BMJ 2020;370:m3379). The first version of this living guidance focuses on corticosteroids. Available on the BMJ website.
  • Vaccine development pipeline: see COVID-19, Prevention for summary of vaccine development and clinical trials.

New Drug Approvals

  • Inmazeb*, a combination of three monoclonal antibodies (atoltivimab, maftivimab, and odesivimab-ebgn in a 1:1:1 ratio), approved by the US FDA for the treatment of infection caused by Zaire ebolavirus in adult and pediatric patients, including neonates born to a mother who is RT-PCR positive for Zaire ebolavirus infection. Recommended dosage: 50 mg of atoltivimab, 50 mg of maftivimab, and 50 mg of odesivimab per kg IV as a single infusion. Product availability: single-dose vials, 241.7 mg of each antibody per 14.5 mL.

New or Updated Treatment Guidelines

Practice Pearls from the Recent Literature

  • No data on CSF penetration of ceftolozane-tazobactam have previously been available. In ten critically ill patients with an indwelling external ventricular drain, CSF penetration ratios of ceftolozane and tazobactam were both 0.2, and 3 gm IV q8h achieved a >90% probability of target attainment in the CSF only when MICs were ≤0.25 µg/mL. These data suggest inadequate CSF exposure for gram-negative infection using maximal dosing of ceftolozane-tazobactam unless pathogen MICs are very low (Antimicrob Agents Chemother 2020 Oct 19 [Epub ahead of print]).
  • Pharmacokinetic/pharmacodynamic data for minocycline are limited, given that the drug was approved about a half-century ago. In a PK study in 55 patients, IV minocycline (200 mg IV q12h) was predicted to result in a suboptimal PK/PD profile for Acinetobacter baumannii infection with MIC values ≥1 µg/mL (CLSI susceptibility breakpoint ≤4 µg/mL), emphasizing the importance of considering combination therapy when using minocycline for A. baumannii and raising questions about current interpretive breakpoints (Antimicrob Agents Chemother 2020 Nov 9 [Epub ahead of print]).
  • A patient with COVID-19 administered remdesivir (RDV) developed marked sinus bradycardia on day two of treatment (heart rate 38 bpm, baseline 60-70 bpm). No cardiotoxic drugs in her regimen were identified, and her bradycardia was attributed to COVID-19. After two days of persistent bradycardia with eventual QRS complex widening and other cardiac symptoms, RDV was discontinued and atropine administered. Her bradycardia, widened QRS, and other symptoms resolved rapidly, suggesting a possible rare RDV adverse effect (JACC Case Rep 2020 Oct 28 [Epub ahead of print]).
  • Pharmacokinetic changes commonly associated with extracorporeal membrane oxygenation (ECMO) include increased volume of distribution and alterations in drug clearance. Published data regarding caspofungin have been inconclusive, but two recent studies (in critically ill and lung transplant patients) suggest no significant effect of ECMO on caspofungin pharmacokinetics (Antimicrob Agents Chemother 2020;64:e00345-20Antimicrob Agents Chemother 2020 Aug 17 [Epub ahead of print]).
  • Remdesivir (RDV) is not recommended in its EUA for patients with eGFR <30 mL/min in part because the drug vehicle, sulfobutylether-β-cyclodextrin (SBECD), may accumulate to toxic concentrations. However, each 100 mg of lyophilized powder and solution of RDV contain only 3 gm and 6 gm of SBECD, respectively, compared to the maximum recommended safety threshold of 250 mg/kg/day for SBECD. Although conclusive safety data in patients with eGFR <30 mL/min are lacking, the recommended 5-10 day RDV treatment duration and relatively low concentrations of SBECD suggest benefit may outweigh risk, particularly since SBECD is readily removed by hemodialysis and CRRT (J Am Soc Nephrol 2020;31:1384).

Drug Shortages (US)

  • Antimicrobial drugs or vaccines in reduced supply or unavailable (as of November 10, 2020) due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons:
    • New on the list since October 13None
    • Shortage recently resolvedMetronidazole injection
    • Antibacterial drugs in continued reduced supply:
      • Aminoglycosides: Amikacin injection, Tobramycin injection, Tobramycin lyophilized powder for injection
      • Carbapenems: Meropenem injection
      • Cephalosporins: Cefazolin injection, Cefepime injection, Cefotaxime injection (FDA is allowing temporary importation of product from SteriMax in Canada, in conjunction with Apollo Pharmaceuticals and its distributor FFF Enterprises. Click here for details), Cefotetan injection, Cefoxitin injection, Ceftazidime injection, Ceftazidime/avibactam injection
      • Clindamycin injection
      • Fluoroquinolones: Ciprofloxacin 0.3% ophthalmic solution, Gemifloxacin tablets
      • Glycopeptides, glycolipopeptides, lipopeptides: Vancomycin injection
      • Macrolides/azalides: Azithromycin injection, Azithromycin ophthalmic solution 1% (unavailable)
      • Methanamine hippurate tablets
      • Nitrofurantoin oral suspension
      • Penicillins: Ampicillin/sulbactam injection, Piperacillin/tazobactam injection
      • Tetracyclines: Doxycycline injection
      • Topical (miscellaneous) antibacterials: Neomycin and Polymyxin B sulfates GU irrigant, Neomycin and Polymyxin B sulfates and Dexamethasone ophthalmic ointment, Sulfacetamide 10%/Prednisolone 0.2% ophthalmic ointment (unavailable), Sulfanilamide 15% vaginal cream (unavailable)
    • Antimycobacterial drugs
      • Ethambutol tablets
    • Antifungal, antiparasitic, and antiviral drugs in continued reduced supply:
      • Antifungal drugs: Amphotericin B injection, Clotrimazole 10 mg oral troches, Fluconazole injection
      • Antiparasitic drugs: Chloroquine tablets, Hydroxychloroquine tablets, Pentamidine isethionate
      • Antiviral drugs: Acyclovir injection, Cidofovir injection
    • Vaccines in continued reduced supply:
      • Hepatitis B vaccine recombinant, Yellow Fever vaccine (YF-VAX is unavailable, but Stamaril can be obtained through a limited number of clinics in the US. Click here).
  • Antimicrobial drugs newly discontinued: 
    • Recent discontinuations: Mupirocin calcium 2% cream (Bactroban [GSK], in June 2020), Bacitracin injection (in February 2020), Interferon alfa-2b (Intron A, in October 2019), Mupirocin calcium 2% nasal ointment (Bactroban Nasal [GSK], in August 2019), Quinidine gluconate IV (in December 2017), Terbinafine granules (in May 2017), 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).