ID Update

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.

MARCH 2014

Recent Literature

  • 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).

Drug Safety

  • 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.

FEBRUARY 2014

Recent Literature

  • 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

JANUARY 2014

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.

Recent Literature

  • 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.

DECEMBER 2013

New or Updated Practice Guidelines

  • 2013 IDSA Clinical Practice Guideline for Vaccination of the Immunocompromised Host. Evidence-based guidelines for active immunization of immunocompromised patients and their household contacts (CID 58:e44, 2013). Advance Access published online December 4 on IDSA website.
  • Primary Care Guidelines for the Management of Persons Infected with HIV: 2013 Update by the HIV Medicine Association of the IDSA (CID 58:e1, 2014). Last update was in 2009.

Recent Literature

  • Combination therapy with Vancomycin plus an antistaphylococcal penicillin or first-generation cephalosporin for empirical treatment of Staph. aureus bacteremia: what's the evidence? (CID 57:1760, 2013).
  • The "quad pill," the third once-daily, single-pill regimen for HIV, is reviewed. It is the first such therapy to include an integrase inhibitor (Elvitegravir), and it also contains Cobicistat, a novel CYP3A4 inhibitor used for pharmacokinetic boosting (CID 58:93, 2014).
  • Tedizolid may be the first oxazolidinone to be approved for clinical use in the U.S. since Linezolid in 2000. Learn about it in a Clinical Infectious Diseases supplement (CID 58(Suppl 1):S1-S57, 2014).
  • Inhaled antibiotics play an important role in the management of cystic fibrosis. A new review summarizes the pharmacology, PK/PD, clinical efficacy, and toxicity of inhaled Aztreonam (Expert Opin Pharmacother 14:2115, 2013).
  • Fluoroquinolones have been linked to an increased risk of retinal detachment, but a large study using data from Danish national registries finds no such association (JAMA 310:2184, 2013).

New Drug Approvals for Chronic Hepatitis C

  • Simeprevir (Olysio), an HCV NS3/4A protease inhibitor. Efficacy was established in combination with Peginterferon alfa plus Ribavirin in genotype 1 infected patients with compensated liver disease, including cirrhosis. The dose is 150 mg po qd with food.
  • Sofosbuvir (Sovaldi), a nucleotide analog inhibitor of the HCV NS5B RNA-dependent RNA polymerase.  Used in combination with Ribavirin or Pegylated interferon + Ribavirin.  The dose is 400 mg po qd with or without food.

New Dosage Forms or Indications

  • Posaconazole, previously marketed as an oral suspension, is now available in 100 mg delayed-release tablets. This new formulation is indicated only for prophylaxis of invasive Candida and Aspergillus infection. The approved tablet dose is 300 mg bid on day 1, then 300 mg qd (with food).

New in the Guide this Month

  • New drug pages: Simeprevir, Sobosfuvir
  • New table: Inhalation Antibiotics

NOVEMBER 2013

New or Updated Practice Guidelines

Recent Trials and Reviews

  • Bad news about probiotics: In a multicenter, randomized, double-blind, placebo-controlled trial conducted in inpatients ≥65 years old exposed to ≥1 oral or parenteral antibiotics, a multistrain preparation of lactobacilli and bifidobacteria was ineffective in preventing antibiotic-associated diarrhea or C. difficile infection (Lancet 382:1249, 2013).
  • Flucytosine was first used for human cryptococcal infection in 1968. The pharmacology and current role of this venerable compound for cryptococcosis is summarized (JAC 68:2435, 2013).
  • In a randomized, placebo-controlled, double-blind multicenter trial performed in French ICU patients with suspected ventilator-associated pneumonia, adjunctive simvastatin (60 mg daily) did not improve 28-day mortality nor any secondary outcome (JAMA 310:1692, 2013).
  • Cobicistat, a specific CYP3A inhibitor with no intrinsic activity against HIV, is part of a single-tablet regimen that includes Elvitegravir, Emtricitabine, and Tenofovir. This review summarizes its pharmacology, clinical data, and role in therapy (Pharmacother 33:1107, 2013).

Drug Safety

  • Continued reports of patients receiving rituximab or ofatumumab who experience hepatitis B (HBV) reactivation have prompted FDA-approved labeling changes. HBV reactivation has been added to the existing Boxed Warning for rituximab, and a new Boxed Warning has been created for ofatumumab.

New Drug Approvals

  • Luliconazole 1% cream (Luzu), a topical imidazole, for interdigital tinea pedis, tinea cruris, and tinea corporis caused by T. rubrum and E. floccosum in patients ≥18 years old. Topical luliconazole has been available in Japan since 2005.

New Dosage Forms or Indications

  • Econazole 1% topical foam (Ecoza) for interdigital tinea pedis caused by T. rubrum, T. mentagrophytes, and E. floccosum in patients ≥12 years old. Econazole has been available in the U.S. as 1% cream.
  • The FDA recently expanded the age indication for the quadrivalent meningococcal vaccine Menveo to ≥2 months old. Menveo protects against serogroups A, C, W-135, and Y (not B). It was previously approved for patients ≥2 years old (Med Lett 55:92, 2013).

Other Drug Development News

  • On October 24 Cubist Pharmaceuticals completed its acquisition of Optimer Pharmaceuticals, including the rights to fidaxomicin. Antimicrobials in the Cubist pipeline now include tedizolid, ceftolozane/tazobactam, and surotomycin.

New in the Guide this Month

  • Significant updates across the board in conjunction with the annual updates to the print editions.