July 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 received this message from a colleague, subscribe now.

July 2019

New Antimicrobial Drug Approvals

  • Recarbrio (imipenem/cilastatin/relebactam), approved for patients ≥18 years of age who have limited or no alternative treatment options for complicated urinary tract infections (including pyelonephritis) and complicated intra-abdominal infections. Imipenem is a carbapenem, cilastatin is an inhibitor of renal dehydropeptidase, and relebactam is a beta-lactamase inhibitor. Recommended dosage, normal renal function: 1.25 gm (imipenem 500 mg, cilastatin 500 mg, relebactam 250 mg) IV q6h. Note that the cilastatin is included in the dosage of this product, unlike imipenem/cilastatin.

New or Updated Treatment Guidelines

  • Clinical practice guidelines for the management of chronic hepatitis B, from the Korean Association for the Study of the Liver (KASL) (Clin Mol Hepatol 25:93, 2019). These guidelines update the 2015 release and are available on the journal website.

Practice Pearls

  • We would not expect drug-drug interactions to be a significant issue with clotrimazole troches, given the poor oral absorption of clotrimazole from that formulation. However, a heart transplant patient receiving everolimus (a CYP3A4 and P-glycoprotein substrate) for rejection prevention and clotrimazole troches 10 mg qid for thrush prophylaxis experienced a sharp drop in everolimus trough concentrations (8.4 to 2.5 ng/mL) following the discontinuation of clotrimazole (calculated oral clearance of everolimus increased from 6.0 to 11.2 L/hr). A similar phenomenon has been observed in patients treated with tacrolimus (also a CYP3A4 and P-gp substrate) and clotrimazole troches, and it may have contributed to graft rejection. In another study, clotrimazole troches reduced the oral clearance of midazolam (a CYP3A4 substrate) without affecting systemic clearance. A plausible explanation is that clotrimazole achieves sufficient intestinal concentrations to inhibit presystemic clearance and thus enhance everolimus bioavailability (by inhibiting intestinal CYP3A4 and/or P-gp), but it achieves insufficient concentrations in the hepatic circulation to inhibit hepatic CYP3A4 and/or P-gp (Br J Clin Pharmacol 2019 June 26 [Epub ahead of print]).

Drug Shortages (US)

  • Antimicrobial drugs or vaccines in reduced supply or unavailable (as of July 1, 2019) due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons:
    • [New on the list since June 11]: None
    • [Shortage recently resolved]: Amphotericin B injection, Nelfinavir tablets
    • [Continue to be in reduced supply]:
      • Aminoglycosides: Amikacin injection, Gentamicin ophthalmic ointment (unavailable), Tobramycin injection
      • Carbapenems: Meropenem injection
      • Cephalosporins: Cefazolin injection, Cefepime injection, Cefotaxime injection (unavailable), Cefoxitin injection, Ceftazidime injection, Ceftriaxone injection, Cefuroxime injection
      • Fluoroquinolones: Ciprofloxacin 0.3% ophthalmic solution, Ciprofloxacin oral suspension, Gemifloxacin tablets
      • Glyco-, glycolipo-, lipopeptides: Daptomycin injection, Vancomycin injection
      • Macrolides/azalides: Azithromycin injection, Azithromycin ophthalmic solution 1% (unavailable), Erythromycin lactobionate injection (unavailable), Erythromycin 0.5% ophthalmic ointment
      • Penicillins: Ampicillin/sulbactam injection, Piperacillin/tazobactam injection
      • Tetracyclines: Doxycycline hyclate injection
      • Other antibacterials: Clindamycin injection, Metronidazole injection, Mupirocin calcium 2% cream, Mupirocin calcium 2% nasal ointment (unavailable), Nitrofurantoin oral suspension, Sulfanilamide 15% vaginal cream (unavailable)
      • Antifungal drugs: Clotrimazole 10 mg oral troches, Fluconazole injection, Nystatin oral suspension
      • Antiparasitic drugs: Pentamidine isethionate
      • Antiretroviral drugs: None
      • Antiviral drugs: Cidofovir injection (unavailable), Letermovir injection (unavailable), Valganciclovir oral powder for solution
      • Vaccines: Hepatitis A vaccine inactivated, Hepatitis B vaccine recombinant, Zoster vaccine recombinant (Shingrix), Yellow Fever vaccine (YF-VAX is unavailable, but Stamaril can be obtained through a limited number of clinics in the US. Click here).
  • Antimicrobial drugs newly discontinued: Quinidine gluconate IV (in December 2017). Product distribution will continue until expiration of current stock (March 2019).
    • 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)
  • For detailed information including estimated resupply dates, see http://www.ashp.org/menu/DrugShortages