Sanford Guide

ID Update

  • 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.

DECEMBER 2014

New Drug Approvals

  • In late November the European Commission approved the once-daily fixed-dose antiretroviral therapy Rezolsta (darunavir 800 mg + cobicistat 150 mg). The combination was approved in Canada in June (as Prezcobix).

Recent Literature

  • Cephalosporins seem to have a predilection for inducing immune hemolytic anemia (IHA). Big offenders are cefotetan and ceftriaxone. The majority of cases of IHA in ceftriaxone-treated patients have been reported in children. Outcomes can be serious (Ann Pharmacother 48:1594, 2014).
  • Currently available HBV treatment options suppress viral replication but do not eradicate the virus. Two recent reviews can help clinicians determine who needs treatment now vs. who can be monitored with treatment deferred (Clin Gastroenterol Hepatol 12:16, 2014; Lancet 384:2053, 2014).
  • Trachoma is the most common infectious cause of blindness. A 1997 WHO resolution established the Global Alliance for the Elimination of Blinding Trachoma by 2020 (GET 2020). The GET campaign utilizes the SAFE strategy for management and prevention: Surgery, Antibiotics, Facial cleanliness, and Environmental improvements (Lancet 384:2142, 2014).
  • Getting to know a pathogen: non-typeable H. influenzae. Non-typeable Haemophilus influenzae has never had the high profile of encapsulated strains such as type b (Hib). However, increased prominence as a pathogen and the emergence and spread of β-lactamase-negative ampicillin-resistant strains is attracting attention (Lancet Infect Dis 14:1281, 2014).

NOVEMBER 2014

New Drug Approvals

  • Ledipasvir/sofosbuvir (Harvoni) for chronic hepatitis C genotype I infection, the first approved regimen that does not require administration with interferon or ribavirin.

Recent Literature

  • High-level ceftaroline resistance. This is the first report of high-level resistance (MIC >32) to ceftaroline in a clinical MRSA isolate, apparently due to two amino acid substitutions in the ceftaroline binding pocket of PBP2a (Antimicrob Agents Chemother 58:6668, 2014).
  • Getting to know a microbe: coagulase-negative staphylococci (CoNS). CoNS have become major nosocomial pathogens, particularly in association with indwelling or implanted foreign bodies. Frequent oxacillin resistance and decreasing susceptibility to glycopeptides present therapeutic challenges (Clin Micro Rev 27:870, 2014).
  • Daptomycin for VRE bacteremia: unproven. Clinical efficacy data for treatment of VRE bacteremia and endocarditis using daptomycin are limited mainly to case series and retrospective cohorts. Higher-than-approved doses (8-12 mg/kg/day) seem important and combination therapy with beta-lactams is intriguing. Prospective clinical trials are desperately needed (Int J Antimicrob Agents 44:387, 2014).
  • Treatment review: syphilis. Penicillin remains the drug of choice for all stages. Current treatment guidelines are based largely on clinical experience and expert opinion rather than rigorous clinical trials, but overall are successful (JAMA 312:1905, 2014).
  • Rabies. Most cases of human rabies occur in Africa and Asia, dog bites are responsible for >99% of cases, and almost 60,000 deaths occur globally each year. The causative lyssaviruses and disease transmission, management, and prevention are reviewed (Lancet 384:1389, 2014).
  • Shorter-course TB treatment using an FQ? Not according to the results of these three trials. Four months of a modified gatifloxacin- or moxifloxacin-containing regimen were less effective than six month standard RIPE therapy in all three (N Engl J Med 371:1577, 2014; N Engl J Med 371:1588, 2014; N Engl J Med 371:1599, 2014).

Updated Practice Guidelines

OCTOBER 2014

EVD Update

  • Updated CDC advisory in wake of case diagnosed in Dallas, TX, in late September 2014:
    • Increase vigilance in inquiring about travel history (to/from West Africa) in 21 days before onset of symptoms (fever, nausea, vomiting);
    • Isolate persons with travel history to an EVD affected country (Liberia, Sierre Leone, Guinea) and who are exhibiting symptoms: private room, private bath + standard healthcare worker protections (gown, mask, eye protection, gloves);
    • Notify local/state health department immediately.

New Drug Approvals

  • Elvitegravir (Vitekta), the INSTI component of the four-drug combination Stribild, is now available as a single agent. It is intended for use in "failure" regimens that include a protease inhibitor, ritonavir, and another antiretroviral agent, and can be used in patients with poor renal function.
  • Cobicistat (Tybost) has been approved for boosting of atazanavir or darunavir in combination with other antiretroviral agents for the treatment of HIV infection.

Recent Literature

  • Carbapenem-penicillin cross-allergy update. Retrospective data from 838 patients with a clinical history of IgE-mediated penicillin hypersensitivity who were administered a carbapenem provide further evidence that cross-allergy is unlikely. Caution remains prudent (Clin Infect Dis 59:1113, 2014).
  • Daptomycin plus statins. Data from a multicenter, retrospective study suggest similar rates of musculoskeletal toxicity in patients treated with daptomycin plus a statin (n=49) vs. daptomycin alone (n=171). Simvastatin was the most commonly used statin (Antimicrob Agents Chemother 58:5726, 2014).
  • Getting to know a microbe: Aspergillus terreus. A. terreus is known for intrinsic resistance to amphotericin B. A relatively high percentage of clinical isolates exhibit acquired resistance to azoles, particularly voriconazole. Posaconazole is more promising (Int J Antimicrob Agents 44:281, 2014).
  • Legionnaires' Disease. Global epidemiology, diagnosis and management, and research needs and priorities are summarized (Lancet Infect Dis 14:1011, 2014).

SEPTEMBER 2014

Recent Literature

  • Combination therapy for neurocysticercosis. In patients with multiple brain cysts, the antiparasitic efficacy of albendazole + praziquantel was superior to that of albendazole alone, without increased side effects (Lancet Infect Dis 14:687, 2014).
  • Further evidence that artemether-lumefantrine is safe in early pregnancy. No attributable adverse effects were observed in 164 pregnant Tanzanian women inadvertently administered artemether-lumefantrine during first trimester. In contrast, quinine exposure was associated with adverse outcomes (Malaria J 13:197, 2014)

AUGUST 2014

CDC Guidelines for US Patients with Possible EVD

  • The latest CDC Health Advisory provides 1) updated guidance to healthcare providers and state and local health departments regarding who should be suspected of having Ebola Virus Disease (EVD), 2) clarifies which specimens should be obtained and how to submit for diagnostic testing, and 3) provides hospital infection control guidelines.

Chikungunya virus in the US

  • From 2006‒2013, about 28 people/year in the US tested positive for recent chikungunya virus infection. All were travelers visiting or returning to the US from affected areas. As of August 5, 484 cases have been reported to ArboNET in 2014, 472 of which have occurred in travelers returning from affected areas in the Caribbean or South America. Weekly updates of case counts and other information can be found here.

New Drug Approvals

  • Oritavancin (Orbactiv) has been approved for the treatment of adults with skin and skin structure infections caused by susceptible Gram-positive cocci, including MRSA. Oritavancin has a long terminal half-life (245 hr) that allows for one-time dosing.
  • Triumeq, a combination of dolutegravir, abacavir, and lamivudine, has been approved for treatment of HIV-1 infection. It is the fourth all-in-one combination product to be approved by the FDA and the only one to not include tenofovir. Dolutegravir is an integrase strand transfer inhibitor (INSTI), and abacavir and lamivudine are nucleoside reverse transcriptase inhibitors.

Recent Literature

  • Drug of the month: fosfomycin. This venerable compound has in vitro activity against ESBL-producing Enterobacteriaceae, CRE, and possibly MDR Pseudomonas. Lack of an IV formulation in the US and a paucity of clinical trials are limitations, but further study seems warranted (Pharmacotherapy 34:845, 2014).
  • Getting to know a microbe: Rothia. Ten years of experience with Rothia bacteremia at the Mayo Clinic is reviewed. All of the clinical bloodstream infections were caused by R. mucilaginosa, and all tested isolates were susceptible to vancomycin and most beta-lactams. Four of six tested isolates were oxacillin-resistant, however (J Clin Microbiol 52:3184, 2014).
  • Side effect corner: carbapenems and seizures. The first meta-analysis to describe the comparative epileptogenicity of imipenem, meropenem, ertapenem, and doripenem shows a higher rate of seizures among carbapenem recipients compared to patients receiving non-carbapenems. However, meaningful conclusions regarding the seizure risk specifically attributable to each drug remain elusive (J Antimicrob Chemother 69:2043, 2014).
  • Treatment overview: life without a spleen. Successful prevention of fatal postsplenectomy sepsis requires education, vaccination, prophylactic antibiotics in certain patients, and early empiric therapy for febrile episodes (N Engl J Med 371:349, 2014).

Updated Practice Guidelines

  • The IDSA has updated its 2005 guidelines for the diagnosis and management of skin and soft tissue infections (Clin Infect Dis 59:e10, 2014).
  • A new policy statement updates the American Academy of Pediatrics recommendations for the use of meningococcal vaccines in children and adolescents (Pediatrics 134:400, 2014).

JULY 2014

New HIV laboratory testing recommendations from CDC

  • The CDC has issued updated recommendations for laboratory testing for HIV infection. Testing begins with a combination immunoassay that detects HIV-1 and HIV-2 antibodies and HIV-1 p24 antigen; positive specimens undergo supplemental testing with an immunoassay that differentiates HIV-1 from HIV-2 antibodies. The new algorithm allows diagnosis up to 3-4 weeks earlier than the previously recommended sequence of tests using the Western blot.

Recent Literature

  • There were more cases of pertussis in the US in 2012 than in any year in the last half-century. Antibiotics are used mainly to prevent spread. The authors review advances in the epidemiology, diagnosis, treatment, and prevention of this ancient disease (Chest 146:205, 2014).
  • Human infection caused by Bartonella spp. (mainly B. henselae, B. quintana, and B. bacilliformis) presents a treatment challenge. Relapses occur frequently due to an intraerythrocytic phase that provides a protective niche for the microbe. This review summarizes recent data and treatment recommendations based on pathogenicity (Int J Antimicrob Agents 44:16, 2014).
  • Successful treatment of mold infection of the central nervous system involves early diagnosis, appropriate antifungal therapy, neurosurgical assessment and intervention, and management of host immunologic impairment. The epidemiology, microbiology, clinical manifestations, and therapy of infection caused by Aspergillus, Fusarium, Scedosporium, Mucorales, and dematiaceous fungi are reviewed (N Engl J Med 371:150, 2014).
  • Significant interpatient variability in voriconazole plasma concentrations results from genetic polymorphism of the major metabolizing enzyme CYP2C19 as well as nonlinear pharmacokinetics, drug interactions, and the effect of concomitant liver disease. Is it time for initial dose selection to be guided by CYP2C19 genotype? (Pharmacotherapy 34:703, 2014.)

JUNE 2014

Ebola outbreak, West Africa: update

  • The ongoing Ebola viral disease (EVD) outbreak in West Africa is now the largest outbreak ever documented. As of June 18 there have been 528 cases (laboratory-confirmed, probable, and suspected) and 337 deaths reported in Guinea, Liberia, and Sierra Leone. More information can be found on the CDC MMWR homepage.

New Drug Approvals

  • Efinaconazole (Jublia) 10% solution is the first triazole approved for the topical treatment of toenail onychomycosis due to T. rubrum and T. mentagrophytes.
  • Tedizolid (Sivextro), an oxazolidinone, has been approved for oral and IV treatment of skin and skin structure infections including those caused by MRSA. Its 12 hour elimination half-life allows for once-daily dosing.

Recent Literature

  • Published information on daptomycin bone penetration is scant. Limited data obtained from 16 patients undergoing knee or hip replacement suggest clinically useful penetration of bone and synovial fluid (Antimicrob Agents Chemother 58:3991, 2014).
  • Colistin and polymyxin B have essentially identical antibacterial spectra, with cross-resistance existing between the two drugs. However, polymyxin B has superior pharmacological properties. Nation, et al, summarize the key differences (Clin Infect Dis 59:88, 2014).
  • Dalbavancin and oritavancin are lipoglycopeptides with concentration-dependent killing and terminal half-lives >2 weeks, properties that allow for convenient dosing. In separate trials, dalbavancin administered in two weekly doses and oritavancin given as a single dose were non-inferior to twice-daily vancomycin for skin and skin structure infections (N Engl J Med 370:2169, 2014; N Engl J Med 370:2180, 2014; editorial: N Engl J Med 370:2238, 2014).

MAY 2014

CDC Health Advisory: MERS-CoV

  • CDC has confirmed the first US case of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection, identified in a traveler (details here). Clinicians should be vigilant for MERS-CoV in patients with respiratory disease returning from the Middle East.

New Drug Approval

  • Dalbavancin (Dalvance) has been approved for the treatment of adults with Gram-positive skin and skin structure infections, including MRSA.

Recent Literature

  • Macrolide antibiotics are known to cause ventricular arrhythmias by prolonging the QT interval. A review of recent literature suggests that the risk of arrhythmias in the absence of other risk factors is very low. Taking a thorough history and performing an EKG before and during therapy should allow for safe use of chronic macrolides in most patients for whom they are recommended (Am J Respir Crit Care Med 189:1174, 2014).
  • Published data assessing cross-reactivity between penicillins and cephalosporins for non-IgE-mediated hypersensitivity reactions (HSR) are scant. Retrospective data from an outpatient parenteral antimicrobial program suggest that cefazolin is well tolerated in patients who have experienced a non-IgE-mediated HSR to nafcillin (Antimicrob Agents Chemother 58:3137, 2014).
  • The pathogenesis, clinical manifestation, diagnosis, and treatment of antibiotic hypersensitivity reactions are reviewed, as well as basic principles of desensitization (Clin Infect Dis 58:1140, 2014).
  • Brazil will host the 2014 FIFA World Cup and the 2016 Olympic and Paralympic Games. Data (primarily about infectious diseases) collected from ill travelers returning from Brazil in 1997-2013 is presented to 1) assist clinicians who are advising prospective travelers to these events regarding pretravel preparation, and 2) help focus posttravel illness workup (Clin Infect Dis 58:1347, 2014).

Updated Practice Guidelines

  • The DHHS Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents have been updated and are available at the AIDSinfo clinical guidelines portal.

APRIL 2014

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/sofosbuvir fixed dose combination tablet, with or without ribavirin, for chronic hepatitis C (genotype 1) have been published in the New England Journal of Medicine. Sofosbuvir, a nucleotide analog inhibitor of the HCV NS5B RNA polymerase, was FDA-approved late last year. Approval of the combination of sofosbuvir 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 US 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 infections, and the dose is 300 mg IV bid on day 1, then 300 mg IV qd.