ID Update™: Sanford Guide News
- ID Update™ is the Sanford Guide infectious diseases news page.
- Each month, we summarize new or updated practice guidelines, recent clinical trials, new reviews, relevant drug safety notices, new drug approvals, new dosage forms, new treatment indications and other current developments.
Ebola outbreak, West Africa
- There is currently an outbreak of Ebola viral disease in Guinea and Liberia. A summary of the situation from the US CDC can be found here. Advice for travelers from the European CDC can be found here.
Updated Practice Guidelines
Hepatitis C News
- Three large trials (ION-1, ION-2, ION-3) of a ledipasvir/sobosfuvir fixed dose combination tablet, with or without ribavirin, for chronic hepatitis C (genotype 1) have been published in the New England Journal of Medicine. Sobosfuvir, a nucleotide analog inhibitor of the HCV NS5B RNA polymerase, was FDA-approved late last year. Approval of the combination of sobosfuvir plus ledipasvir, a potent HCV NS5A inhibitor, is expected by fall (ION-2: N Engl J Med 370:1483, 2014; ION-1 and ION-3 are published online).
Other Recent Literature
- Drawz et al review recent advances in beta-lactamase inhibitors including avibactam and MK-7655 (effective against ESBLs, AmpC, and KPC enzymes). Avibactam will likely be the first inhibitor introduced in the U.S. since piperacillin-tazobactam in 1993 (Antimicrob Agents Chemother 58:1835, 2014).
- Current literature supports an association between voriconazole exposure and cutaneous squamous cell carcinoma in lung transplant recipients. The mechanism is unestablished but may involve the drug's primary metabolite, voriconazole N-oxide (Clin Infect Dis 58:997, 2014).
- The incidence of skin abscesses has increased, and MRSA is a dominant cause. Management of abscesses is reviewed (N Engl J Med 370:1039, 2014).
New Drug Approvals
- Miltefosine (Impavido) has been approved for treatment of visceral, cutaneous, and mucosal leishmaniasis in patients ≥12 years of age.
New Dosage Forms
- Metronidazole 1.3% vaginal gel is a new single-dose option for bacterial vaginosis (BV). Metronidazole 0.75% gel, one applicator-full at bedtime x 5 days, has been the CDC recommendation for topical treatment of BV.
- Posaconazole, previously marketed as delayed-release tablets and oral suspension, is now available in an intravenous formulation (300 mg/vial). The approved indication is prophylaxis of invasive Aspergillus and Candida infection, and the dose is 300 mg IV bid on day 1, then 300 mg IV qd.
- Interesting but limited in vitro observations suggest that ceftaroline may potentiate the activity of daptomycin against VRE, including daptomycin-nonsusceptible strains. No supportive clinical data exist at present (Antimicrob Agents Chemother 58:1494, 2014).
- In ambulatory patients stabilized on warfarin, URI increased the risk of excessive anticoagulation independent of antibiotic use. Antibiotics further increased the risk but the difference was not statistically significant. Inhibitors of warfarin metabolism (metronidazole, TMP-SMX) were the biggest offenders (JAMA Intern Med 174:409, 2014).
- Based on its review of a clinical trial comparing doripenem to imipenem/cilastatin for ventilator-associated pneumonia (prematurely terminated in 2011), the FDA has approved changes to the doripenem prescribing information warning of an increased risk of death and lower clinical cure rate in the doripenem study arm. Clinicians were first notified of these results in January 2012. Doripenem is not approved for any type of pneumonia.
- Vancomycin efficacy and toxicity are probably both related to AUC. Because trough-only monitoring without a Bayesian tool is a poor surrogate for AUC estimation, inferior dose selection may result (Antimicrob Agents Chemother 58:309, 2014).
- Fosfomycin may be a treatment alternative for prostatic infection due to MDR gram-negative bacilli, since prostate concentrations are reasonable (Clin Infect Dis 58:309, 2014).
- Limbago, et al, describe the 13th VRSA isolate to be identified in the U.S. since the first case was recognized in 2002. This latest isolate is the first to be community-associated (J Clin Microbiol 52:998, 2014).
- Improperly managed acute osteomyelitis can have devastating consequences. Diagnosis and treatment of this disease in children is reviewed (N Engl J Med 370:352, 2014).
New in the Guide this Month
- New table: revised Photosensitivity data
New or Updated Practice Guidelines
- The American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA), in collaboration with the International Antiviral Society-USA (IAS-USA), has produced new guidelines for the use of novel HCV therapies (with a particular focus on the new direct-acting agents). See http://www.hcvguidelines.org.
- More conflicting data: a new study finds an association between certain oral fluoroquinolones and the subsequent development of rhegmatogenous retinal detachment (CID 58:197, 2014).
- Daptomycin was approved for clinical use by the FDA in 2004. Its mode of action and mechanisms for nonsusceptibility are reviewed in exquisite detail (Clin Micro Rev 26:759, 2013).
- Antibiotics such as Amoxicillin-Clavulanate and Isoniazid are among the most common causes of idiosyncratic drug-induced liver injury, the topic of a recent review (Mayo Clin Proc 89:95, 2014).
- Antiviral drugs effectively treat acute varicella and herpes zoster, but postherpetic neuralgia continues to present management challenges. The wide range of treatment options for varicella-zoster infection is reviewed (Expert Opin Pharmacother 15:61, 2014).
- Currently available drugs for genital herpes target viral DNA polymerase. Pritelivir, an inhibitor of the viral helicase-primase enzyme complex, is found to suppress viral shedding and lesion development in a recent dose-escalation study (NEJM 370:201, 2014).
New Dosage Forms
- Raltegravir 100 mg/5 mL oral suspension (single-use packets). Previously available as film-coated and chewable tablets.