November ID Update

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Links marked with an asterisk (*) provide details to Sanford Guide Web Edition subscribers, while all other links are universal.

 

New Drug Approval

  • Tenofovir alafenamide (Vemlidy)* has been approved by the FDA for the treatment of chronic hepatitis B in adults with compensated liver disease. The recommended dosage is 25 mg orally once daily with food. Product availability: 25 mg tablets.

 New Dosage Form Approval

  • The FDA has approved Maraviroc(Selzentry) 20 mg/mL oral solution, 25 mg tablets, and 75 mg tabletsThe prescribing information has been updated to include use in pediatric patients 2 years of age and older and weighing at least 10 kg.

New Treatment Guidelines

  •  New clinical practice guidelines for the management of leishmaniasis have been prepared by a panel of the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH). The guidelines are available for download on the IDSA website.

Practice Pearls

    • Candida auris, an emerging fungus capable of invasive infection, is associated with high mortality and possible resistance to multiple antifungal drugs. It was first isolated in 2009 from the external ear canal of an inpatient in a Japanese hospital and has since been reported in a number of countries. A recent report describes the first seven US cases of C. auris infection reported to CDC as of August 31. C. auris is a serious concern because accurate laboratory identification requires specialized methods, it tends to be resistant to two or even three antifungal drug classes (azoles, echinocandins, polyenes), and it has caused outbreaks in health care settings. The optimal treatment regimen is not known (MMWR 65:1234, 2016).

 

    • Drug interactions that result in prolongation of the QT interval (QT-DDI) are often discovered many years after the drugs are marketed, suggesting the need for a more efficient strategy. A group of investigators recently mined the FDA Adverse Event Reporting System (FAERS) for signals indicating a QT-DDI. They then combined those data with ECGs from their institutional electronic health records (EHR). An unexpected interaction between lansoprazole (a proton-pump inhibitor) and ceftriaxone* was identified. Mean prolongation of the QTc (corrected QT interval) was 12 ms in males and 9 ms in females; men taking the combination were 1.4 times as likely to have a QTc above 500 ms as men taking a single drug. The largest effects were observed in white males and black females. The investigators then used patch-clamp electrophysiology to show that, in combination, the drugs block the hERG channel (the main mechanism by which drugs prolong the QT interval). As a negative control, no evidence of a QT-DDI was identified in the FAERS or EHR data, or in the electrophysiologic experiments, for the combination of lansoprazole and cefuroxime*. Further class analysis found no evidence in the FAERS or EHR for an interaction between any other cephalosporin and proton-pump inhibitor. The mechanism for this intriguing drug interaction, identified using a novel approach of data mining followed by laboratory experimentation, is not known (J Am Coll Cardiol 68:1756, 2016).

 

    • Many clinical trials have evaluated the use of cranberry products for UTI prevention, with inconsistent results (often negative, or positive results with flawed methodology). A recent report in JAMA describes a well-designed randomized, double-blind, placebo-controlled trial in elderly female nursing home residents intended to evaluate the effect of cranberry capsules on clinical and microbiologic outcomes. Study participants were administered two oral cranberry capsules (each capsule containing 36 mg of the active ingredient proanthocyanidin) or placebo once a day for a year. There was no significant difference in the primary outcome of bacteriuria plus pyuria, and also no significant differences in any of the secondary outcomes of the study such as symptomatic UTI, rates of death, or hospitalizations. The results of this study are consistent with the view that cranberry products cannot, at this time, be recommended for UTI prevention on the basis of proven benefit (JAMA 316:1879, 2016).

 

  • Vancomycin*-induced thrombocytopenia, first described in 1985, is uncommon, poorly characterized, and probably under-diagnosed. The mechanism appears to involve vancomycin-dependent, platelet-reactive antibodies (N Engl J Med 356:904, 2007). A group of researchers conducted a systematic search of the English-language literature using the PubMed, Scopus, and Web of Science databases; 29 case reports, five observational studies, two clinical trials, two letters, and one case series were identified for analysis and the results were recently published. In summary, the precise incidence of vancomycin-induced thrombocytopenia remains unclear. The reaction appears to be duration-dependent with a mean time to platelet nadir of eight days after the first exposure (and significantly shorter in cases of re-exposure). Nadir platelet counts ranged from 2,000 to 100,000 in patients who experienced bleeding. In the case reports, vancomycin-specific antibodies were detected in 13 of 17 patients who were tested. No conclusive association between vancomycin serum concentration and thrombocytopenia was observed. The platelet count returned to normal in a mean time of 5-6 days following discontinuation of vancomycin. Platelet transfusions were used in some patients with variable results; other measures such as corticosteroids, intravenous immunoglobulin, or rituximab were employed in a few patients with unclear benefit (Drug Safety 2016 Nov 15 [Epub ahead of print]).

Drug Shortages (US)

    •  Antimicrobial drugs or vaccines in reduced supply due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons:
      • [New on the list]: Cefoxitin injection, Cefuroxime injection
      • [Continue to be in reduced supply]: Amikacin, Ampicillin injection, Ampicillin/sulbactam, Cefepime, Cefotetan, Ceftazidime, Ceftriaxone, Chloroquine tablets (250, 500 mg), Ciprofloxacin oral suspension, Clindamycin injection, Erythromycin lactobionate injection, Gentamicin injection, Haemophilus B conjugate vaccine, Meningococcal vaccines (various), Mupirocin calcium 2% cream, Ofloxacin 0.3% ophthalmic solution, Oxacillin injection, Penicillin G benzathine, Piperacillin/tazobactam, Poliovirus vaccine inactivated, Tigecycline, Tobramycin, Vancomycin injection, Yellow Fever vaccine
      • [Shortage recently resolved]: DTaP (Daptacel) vaccine, DTaP-IPV/Hib (Pentacel) vaccine, Imipenem-cilastatin injection

 

    • Antimicrobial drugs currently unavailable due to manufacturing delays or product discontinuation:
      • [New on the list]: None
      • [Continue to be unavailable]: Cefotaxime injection, Ceftazidime/Avibactam injection, Mupirocin calcium 2% nasal ointment, Penicillin G benzathine/Penicillin G Procaine (Bicillin C-R), Penicillin G procaine injection, Penicillin G benzathine 900,000 units/Penicillin G Procaine 300,000 units (Bicillin C-R 900/300)

 

    • Antimicrobial drugs discontinued: 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)