November ID Update

Sanford Guide ID Update features current developments in infectious diseases, curated by the Sanford Guide Editorial Board. Links marked with an asterisk (*) provide details to Web Edition subscribers, while all other links are universal. If you would like to automatically receive our monthly ID Updates by e-mail, subscribe now.
 

NOVEMBER 2017

New Drug Approvals

  • Heplisav-B, a recombinant, adjuvanted two-dose hepatitis B vaccine, for prevention of infection caused by all known virus subtypes in adults ≥18 years of age. Regimen: two 0.5 mL doses IM, one month apart.
  • Letermovir* (Prevymis) for prophylaxis of CMV infection and disease in adult CMV-seropositive recipients of an allogeneic stem cell transplant. The recommended dosage is 480 mg IV or orally once daily, initiated between day 0 and day 28 post-transplant and continued through day 100. Product availability: tablets (240 mg, 480 mg), injection.

New Treatment Guidelines

  • New British Thoracic Society guidelines for the management of non-tuberculous mycobacterial pulmonary disease have been published (Thorax 72 (Suppl 2):ii1, 2017). The guidelines are available for download on the journal website.
  • New clinical practice guidelines for the management of chronic pain in patients living with HIV from the HIV Medicine Association (HIVMA) of the Infectious Diseases Society of America (IDSA) have been published (Clin Infect Dis 65:e1, 2017). The guidelines are available for download on the IDSA website.

Updated Treatment Guidelines

  • The HHS Panel on Antiretroviral Guidelines for Adults and Adolescents has released an updated version of the Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV. The guidelines are available for download on the AIDSinfo website.
  • The Recommendations for the Use of Antiretroviral Drugs in Pregnant Women with HIV Infection and Interventions to Reduce Perinatal HIV Transmission in the United States have also been updated and are available for download on the AIDSinfo website.

Practice Pearls

  • Tetracycline is generally avoided in young children younger than eight years of age in part because of the risk of teeth staining. However, there are important pharmacologic differences among the members of the tetracycline class so generalizations may be inaccurate. In a retrospective study of 39 children (mean age 0-7.9 years) who received empiric doxycycline therapy (10 mg/kg/day x2-3 days then 5 mg/kg/day, mean treatment duration 12.5 days), no tetracycline-like staining or enamel hypoplasia of developing teeth was detected. Two previous studies likewise found no evidence of teeth discoloration following doxycycline treatment (J Antimicrob Chemother 72:2887, 2017).

  • Ciprofloxacin and fluconazole are commonly used for prophylaxis and treatment of infections in patients with hematological malignancies. They are both known for prolonging the QTc interval, a risk factor for the development of potentially lethal ventricular tachyarrhythmias, but how perilous is the combination? In a prospective observational study of 170 patients treated with both drugs, the prevalence of QTc-prolongation (>450 ms in males, >470 ms in females) was low (4.7%, mean prolongation 10.7 ms) and in no patient did the QTc interval exceed 500 ms. No patients experienced complications related to QTc interval prolongation and there were no cases of Torsade de pointes. These data suggest that the QTc-prolonging effect of concomitant ciprofloxacin and fluconazole may not be clinically relevant, and routine ECG monitoring of such patients is probably not necessary (Br J Clin Pharmacol 2017 Oct 22 [Epub ahead of print]).
  • It is relatively unusual for a beta-lactam antibiotic to affect CYP450 enzymes. Nafcillin induces CYP2C9 and CYP3A4, presumably explaining its ability to decrease the hypoprothrombinemic effect of warfarin. Similarly, dicloxacillin has been reported to decrease INR in warfarin-treated patients but the mechanism is unestablished. In a study performed in 12 healthy volunteers using a 5-drug pharmacokinetic cocktail, dicloxacillin (1 gm three times daily x10 days) was found to induce CYP2C9, CYP2C19, and CYP3A4. Details of the mechanism were further investigated in vitro using cryopreserved human liver cells. It is reasonable to be cautious when prescribing dicloxacillin to patients receiving narrow therapeutic index drugs metabolized by these CYP enzymes (Br J Clin Pharmacol 2017 Nov 4 [Epub ahead of print]).
  • The pharmacokinetics of many drugs in patients with cystic fibrosis (CF) are altered relative to healthy persons. Commonly observed changes include enhanced renal clearance, enhanced hepatic clearance, and variation in volume of distribution. In a prospective study of ceftaroline in seven patients with CF (mean age 20.3 years), the mean half-life was 1.1 hours, considerably shorter than the expected half-life of ceftaroline in the non-CF population (2.7 hours). 15 mg/kg (maximum 600 mg) IV q8h resulted in a mean Cmax of 22.7 µg/mL, which was adequate to achieve >60% time above an MIC of 1 µg/mL (the typical MIC90 of ceftaroline vs. MRSA). In comparison, 600 mg IV q12h in the non-CF population results in a Cmax of 21.3 µg/mL. These data provide evidence of accelerated clearance of ceftaroline in CF patients and support an increased dosage regimen (J Cyst Fibros 2017 Nov 2 [Epub ahead of print]).

Drug Shortages (US)

  • Antimicrobial drugs or vaccines in reduced supply or unavailable due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons:
    • [New on the list]: Doxycycline hyclate injection, Moxifloxacin injection
    • [Continue to be in reduced supply]:
      • Aminoglycosides: Amikacin injection, Gentamicin injection, Tobramycin injection
      • Cephalosporins: Cefepime, Cefotaxime injection (unavailable), Cefoxitin, Ceftazidime, Ceftriaxone, Cefuroxime injection
      • Fluoroquinolones: Ciprofloxacin oral suspension, Ofloxacin 0.3% ophthalmic solution
      • Penicillins: Amoxicillin/clavulanate 1000 mg/62.5 mg ER tablets, Ampicillin/sulbactam, Oxacillin injection, Penicillin G benzathine, Penicillin G benzathine 900,000 units/Penicillin G procaine 300,000 units (Bicillin C-R 900/300), Penicillin G benzathine/Penicillin G procaine 1.2 million units (Bicillin C-R), Penicillin G procaine injection (unavailable), Piperacillin/tazobactam
      • Other antibacterials: Clindamycin injection, Erythromycin lactobionate injection (unavailable), Metronidazole injection, Mupirocin calcium 2% cream, Mupirocin calcium 2% nasal ointment (unavailable), Vancomycin injection
      • Antifungal drugs: Fluconazole injection
      • Antiparasitic drugs: None
      • Vaccines: Hepatitis A Virus Vaccine Inactivated (Vaqta), Hepatitis B vaccine recombinant, Yellow Fever vaccine (unavailable)
    • [Shortage recently resolved]: Cefpodoxime oral suspension
  • Antimicrobial drugs newly discontinued: None
    • Recent discontinuations: Terbinafine granules (in May 2017), MenHibrix (in February 2017), Elvitegravir (Vitekta, in December 2016), 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)