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.
Post-licensure Safety Surveillance of Shingrix
- Recombinant adjuvanted zoster vaccine (RZV, Shingrix) was approved in October 2017. It is indicated for prevention of herpes zoster (shingles) in adults aged 50 years and older. The recommended administration schedule is two 0.5 mL intramuscular (IM) doses, given 2-6 months apart. RZV is supplied as two vials that must be combined before administration; one contains the lyophilized antigen and the other contains the liquid adjuvant suspension component. After licensure, CDC and FDA began safety monitoring of RZV in the Vaccine Adverse Event Reporting System (VAERS), a national passive surveillance system for adverse events after administration of US-licensed vaccines.
- The initial safety data from VAERS for the first 8 months of vaccine use, when approximately 3.2 million doses were distributed, are consistent with the safety profile observed in prelicensure clinical trials. VAERS received 4,381 reports of adverse events, a reporting rate of 136 reports per 100,000 doses. Only four reports per 100,000 doses were classified as serious. Pyrexia was reported most frequently (23.6%), followed by injection site pain (22.5%), injection site erythema (20.1%), chills (19.3%), headache (16.7%), fatigue (16.0%), and myalgia (12.1%). 230 vaccination error reports were submitted during the analytic period. 143 (62.2%) of the reports were administration errors, most commonly incorrect route (subcutaneous rather than IM); other errors were administration of only the adjuvant and mixing the lyophilized antigen in the wrong diluent. In several reports, health care providers did not administer the second dose of RZV because of a local or systemic reaction, although such reactions are not unexpected; the effectiveness of a single dose of RZV is not known. Overall, these data concerning postlicensure safety data of RZV are reassuring. Adverse reactions are self-limited and generally should not affect completion of the 2-dose series (Morb Mortal Wkly Rep 68:91, 2019).
- The routine use of antibiotics in asthma exacerbation is not recommended, but we know it happens frequently. The evidence addressing this issue is limited. In a retrospective cohort study of 19,811 patients hospitalized for an asthma exacerbation treated with corticosteroids in 542 acute care hospitals in the US over a two-year period, 8,788 (44.4%) received antibiotics initiated within the first two days of hospitalization (and prescribed for a minimum of two days). The most frequently prescribed antibiotics were macrolides, fluoroquinolones, and third-generation cephalosporins. Compared to patients who did not receive antibiotics, antibiotic-treated patients had a significantly longer hospital stay, higher risk of antibiotic-associated diarrhea, and higher cost of hospitalization. The risk of treatment failure (initiation of mechanical ventilation, transfer to the ICU after day 2, in-hospital mortality, or readmission for asthma) was similar in both groups. These findings support the recommendations of current clinical treatment guidelines and illustrate the need for further research to improve antimicrobial stewardship in asthma (JAMA Intern Med 2019 Jan 28 [Epub ahead of print]).
Drug Shortages (US)
- Antimicrobial drugs or vaccines in reduced supply or unavailable (as of February 2, 2019) due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons:
- [New on the list]: Amphotericin B injection, Pentamidine isethionate (Nebupent) for inhalation
- [Shortage recently resolved]: Oxacillin injection, Penicillin G Procaine injection
- [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 injection, Ciprofloxacin 0.3% ophthalmic solution, Ciprofloxacin oral suspension, Gemifloxacin tablets
- Glyco-, glycolipo-, lipopeptides: Daptomycin injection, Vancomycin injection
- Macrolides: Azithromycin injection, Azithromycin ophthalmic solution 1% (unavailable), Erythromycin lactobionate injection (unavailable)
- Penicillins: Ampicillin/sulbactam injection, Piperacillin/tazobactam injection
- Other antibacterials: Clindamycin injection, Metronidazole injection, Mupirocin calcium 2% cream, Mupirocin calcium 2% nasal ointment (unavailable), Nitrofurantoin oral suspension
- Antifungal drugs: Fluconazole injection, Nystatin oral suspension (unavailable)
- Antiparasitic drugs: None
- Antiviral drugs: Cidofovir injection (unavailable), Letermovir injection, Valganciclovir oral powder for solution
- Vaccines: Hepatitis A virus 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