- 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.
- Getting to know a microbe: Actinomyces. Actinomycosis is an endogenous infection. Twenty-five species of Actinomyces have been identified in humans, half in the past 15 years. Actinomyces spp. tend to be susceptible to Penicillin G, multiple other beta-lactams, and Clindamycin; Metronidazole is intrinsically resistant (Clin Microbiol Rev 28:419, 2015).
- Prolonged infusion of beta-lactam antibiotics is increasing in popularity. There are practical issues to consider: 1) a loading dose may be necessary, 2) drug stability at room temperature can be a limiting factor, 3) the dead space in infusion tubing may be a significant percentage of the drug dose if a small infusion volume is used, and 4) drug-drug incompatibilities can be problematic (Int J Antimicrob Agents 45:461, 2015).
- The mechanism of action of an integrase strand transfer inhibitor (INSTI) involves binding to magnesium at the active site of the integrase enzyme. This renders INSTIs susceptible to chelation-mediated drug interactions with multivalent metal cations. The recommendation for Dolutegravir (DTG) has been to avoid concomitant administration and instead administer the DTG 2 hours before or 6 hours after an antacid or mineral supplement. The data in this paper suggest that DTG can be co-administered with calcium or iron supplements as long as they are taken with a meal (J Clin Pharmacol 55:490, 2015).
- In a randomized, placebo-controlled trial in 785 hospitalized patients with community-acquired pneumonia (CAP), seven days of oral prednisone (50 mg qd) shortened time to clinical stability by 1.4 days. Time to hospital discharge and duration of IV antibiotics were reduced by 1 day without an increase in complications associated with CAP. These findings were independent of PSI class. Hyperglycemia from prednisone should be anticipated (Lancet 385:1511, 2015).
- A marked increase in clinical failures in recent years is challenging the status of Metronidazole as drug of choice for mild-to-moderate C. difficile infection, whereas oral Vancomycin remains superior for the treatment for severe infection. Fecal microbiota transplantation has emerged as a safe and highly effective strategy for treatment of recurrence (N Engl J Med 372:1539, 2015).
For New Users
- We've reorganized the Tools menu to make it more intuitive and user-friendly!
- Desensitization protocols for Ceftaroline and Valganciclovir have been added to our collection. Look in Tools, Adverse Effects & Allergy.
Approved by the FDA
- Isavuconazonium sulfate (Cresemba) for adults with invasive aspergillosis or mucormycosis. Isavuconazonium is the prodrug of isavuconazole, a triazole antifungal. The dose is 200 mg (isavuconazole) IV or po q8h x6 doses, then 200 mg IV or po q24h.
- Extracorporeal membrane oxygenation (ECMO) may influence antibiotic pharmacokinetics. Data in critically ill patients receiving beta-lactams are scant. In a case-control study, ECMO therapy did not significantly influence volume of distribution, half-life, or clearance of Meropenem or Piperacillin-tazobactam (Int J Antimicrob Agents 45:278, 2015).
- Getting to know a microbe: Cryptococcus gattii. Cryptococcosis caused by C. gattii occurs in both immunocompromised and immunocompetent patients. Meningoencephalitis is the most severe clinical manifestation. Treatment involves aggressive management of increased intracranial pressure plus antifungal therapy with Amphotericin B plus Flucytosine. The role of adjunctive dexamethasone is unclear (Lancet Infect Dis 15:348, 2015).
- Drug-resistant microbes can spread widely and with alarming speed. Treatment options may be limited or nonexistent, infection control can be a challenge, and infections are associated with increased mortality and economic costs. Carbapenemase-producing Gram-negative bacilli, such as those harboring KPC or NDM beta-lactamases, have recently emerged and are reviewed (Mayo Clin Proc 90:395, 2015).
- This RCT performed at four US centers located in areas of CA-MRSA endemicity compared Clindamycin (300 mg po tid) and TMP-SMX (two single-strength tablets po bid) for the treatment of uncomplicated skin infections (cellulitis, abscesses >5 cm, or both). All abscesses underwent incision and drainage. No significant differences in efficacy or adverse effects were found (N Engl J Med 372:1093, 2015).
- Within endemic areas for schistosomiasis, children bear the heaviest burden of infection. In 2010 the WHO updated their treatment recommendations for preschool-aged children. This paper discusses current barriers and knowledge gaps in pediatric schistosomiasis control. A pediatric formulation of Praziquantel about to enter clinical trials will be helpful (Pediatrics 135:537, 2015).
For New Users
- New to the Sanford Guide Web Edition or App? Try our handy calculators in the Tools menu. You'll find one for BMI, BSA, CrCl, IBW, MELD score, and unit conversions. There is also a calculator for colistin dosing. The CrCl calculator automatically uses Cockcroft-Gault or Salazar-Corcoran depending on patient body weight.
New Drug Approvals
- Ceftazidime-avibactam (Avycaz) for adults with complicated intra-abdominal infections (in combination with metronidazole) and complicated UTIs including pyelonephritis. The drug received a priority review based on phase II and in vitro data, and as such should be reserved for patients who have limited or no alternative treatment options. The recommended dose in normal renal function is 2.5 gm (ceftazidime 2 gm + avibactam 0.5 gm) IV q8h.
- Dutrebis (lamivudine 150 mg + raltegravir 300 mg) in combination with other antiretrovirals for the treatment of HIV-1 infection. The dose is one tablet twice daily, with or without food. At this time it will be available only in select non-US markets on a country-by-country basis.
- Evotaz (atazanavir 300 mg + cobicistat 150 mg) in combination with other antiretrovirals for the treatment of HIV-1 infection. The dose is one tablet daily with food.
- Prezcobix (darunavir 800 mg + cobicistat 150 mg) in combination with other antiretrovirals for the treatment of HIV-1 infection. The dose is one tablet daily with food.
- High-dose daily rifapentine. In this dose-ranging study, high dose daily rifapentine (10, 15, or 20 mg/kg) substituted for rifampin in the intensive phase (first eight weeks) of pulmonary TB treatment was associated with improved antimycobacterial activity. Daily rifapentine was well tolerated and antimycobacterial activity was strongly correlated with rifapentine exposure (AUC) (Am J Respir Crit Care Med 191:333, 2015).
- Combination therapy for invasive aspergillosis. Hematologic malignancy or hematopoietic stem cell transplant patients with suspected or documented invasive aspergillosis (IA) were randomized to voriconazole with or without anidulafungin. 6-week all-cause mortality was significantly lower in the subgroup in whom the IA diagnosis was established by radiographic findings and positive galactomannan. The observed reduction in overall mortality was not statistically significant, however (Ann Intern Med 162:81, 2015).
- Update on Ebola virus disease. The mainstay of therapy for Ebola virus disease is early recognition, effective isolation, and optimal supportive care. The best known emerging treatment is ZMapp, a combination of three humanized monoclonal antibodies expressed in tobacco plants. Brincidofovir, favipiravir, and a few other drugs are also being investigated. Vaccine trials are underway (BMJ 349:g7348, 2014).
- Review of telavancin. Telavancin is a bactericidal lipoglycopeptide that inhibits bacterial cell wall synthesis and also disrupts cell membrane barrier functions. Limited published data suggest a role in the treatment of bacteremic Staph. aureus infection but additional clinical experience is needed. Nephrotoxicity can be an issue (Clin Infect Dis 60:787, 2015).
- Getting to know a microbe: Clostridium difficile. The incidence and severity of C. difficile infection (CDI) have increased since 2000. Metronidazole 500 mg po tid x10-14 days is recommended for mild-moderate CDI, vancomycin 125 mg po qid x10-14 days (or fidaxomicin 200 mg po bid x10 days if risk of recurrence significant) for more severe disease. Vancomycin 500 mg po qid with or without vancomycin 500 mg po qid, plus metronidazole 500 mg IV q8h, is recommended for severe, complicated CDI (JAMA 313:398, 2015).
- Daptomycin in pediatrics. Daptomycin is not licensed by the FDA or the EMA for use in pediatric patients. The important gaps in our pharmacokinetic and clinical knowledge of the drug in this patient population are summarized (J Antimicrob Chemother 70:643, 2015).
New Drug Approvals
- Ceftolozane-tazobactam (Zerbaxa): indicated for treatment of adults with complicated intra-abdominal infections (in combination with metronidazoIe) and complicated urinary tract infections. It is the fourth new antibacterial drug approved in 2014. The recommended dose is 1.5 gm IV q8h.
- Finafloxacin 0.3% otic suspension (Xtoro): indicated for the treatment of acute otitis externa caused by P. aeruginosa and Staph. aureus in patients age 1 year and older. The recommended dose is 4 drops into the affected ear q12h x7 days.
- Peramivir (Rapivab): an IV neuraminidase inhibitor indicated for the treatment of acute uncomplicated influenza in patients age 18 years and older who have been symptomatic for no more than two days. The recommended dose is 600 mg IV x1.
- Viekira Pak: indicated (with or without ribavirin) for treatment of adults with genotype 1 chronic HCV, including patients with compensated cirrhosis. The product consists of ombitasvir/paritaprevir/ritonavir fixed-dose tablets copackaged with dasabuvir tablets. The recommended dose is two ombitasvir/paritaprevir/ritonavir tablets every morning and one dasabuvir tablet in the morning and evening.
- Clavulanic acid, the first commercially-available beta-lactamase inhibitor, was identified in 1972. Sulbactam emerged in 1978, followed by tazobactam in 1984. New beta-lactamase inhibitors such as avibactam, relebactam, and others are under investigation as companion agents to existing antibiotics. Their future is promising yet uncertain (Ann Pharmacother 49:86, 2015).
- Getting to know a microbe: Kingella kingae. The Gram-negative coccobacillus K. kingae has emerged as an important cause of pediatric bacteremia and bone/joint infection. It is the "K" in HACEK, the acronym for a group of fastidious Gram-negative organisms responsible for about 6% of all cases of endocarditis in the general population. K. kingae tends to be highly susceptible to antibiotics; ceftriaxone is a good choice (Clin Microbiol Rev 28:54, 2015).
- The incidence of traveler's diarrhea (TD) during a 2-week trip is 10-40%. Most cases are caused by bacterial enteropathogens. Antibiotic chemoprophylaxis for TD is not generally recommended. Bismuth or loperamide is usually effective for treatment of mild TD, whereas for moderate to severe TD a fluoroquinolone is typically the best choice. Azithromycin is preferred in areas where Campylobacter is common (JAMA 313:71, 2015).
- Antifungal drugs in pregnancy. Anidulafungin, micafungin, and posaconazole have been approved by the FDA since the last published review of this subject. Additional data regarding other azoles and polyenes have also recently emerged (J Antimicrob Chemother 70:14, 2015).
- Non-anti-infective uses of antimicrobial agents include chronic inflammatory pulmonary and dermatologic disorders, chronic periodontitis, GI dysmotility, rheumatoid arthritis, and malignancy. Most of these uses are not FDA-approved, and the quality of supportive literature varies widely (Mayo Clin Proc 90:109, 2015).
Updated Practice Guidelines
- Revised AASLD/IDSA/IAS-USA hepatitis C treatment guidelines are available. Interferon is no longer recommended for most situations. The direct-acting antiviral (DAA) era is upon us. Click here.
- A Working Party formed by the British Society for Antimicrobial Chemotherapy, British Heart Rhythm Society, British Cardiovascular Society, British Heart Valve Society, and British Society for Echocardiography has developed guidelines relating to the diagnosis, treatment and prevention of implantable cardiac electronic device infection in the UK (J Antimicrob Chemother 70:325, 2015).
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).
- 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).
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.
- 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
- 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.
- 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).