2019 Infectious Disease Update Archive

Table of Contents

NOTE: Links marked with an asterisk (*) provide details to Web Edition subscribers, while all other links are universal.

 

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January 2019 Infectious Disease Update

Sanford Guide Releases New Apps

  • Sanford Guide recently upgraded its systems to support a new generation of mobile apps. Users of the Sanford Guide Collection app will see many improvements immediately, while users of other Sanford Guide apps will see new features become available in the next few months. Among the new features now available to Collection users:
    • Clean and modern look and feel with intuitive user interface and improved visual cues to accelerate navigation.
    • Cloud-based bookmarks and notes are shared between platforms (create a bookmark on one device and it will appear automatically on your other devices).
    • The Spectra of Activity is faster on most devices, and when examining an interaction by tapping on it, Stewardship Assist users can choose to filter down to only the active data set or to view all data sets at once.
    • Stewardship Assist users can now access institutional data by tapping their hospital’s logo on the home screen.

New Parenteral Cephalosporin

  • The US FDA has approved cefiderocol* (Fetroja) for the treatment of adults with complicated UTI, including pyelonephritis*, caused by susceptible strains of E. coli, K. pneumoniae, P. mirabilis, P. aeruginosa, and E. cloacae complex. Cefiderocol functions as a siderophore, chelating ferric ions and taking advantage of the bacterial iron transport system for enhanced accumulation in the bacterial periplasmic space. The drug should be reserved for use in patients with limited or no alternative treatment options. Recommended dosage: 2 gm IV (infused over 3 hours) q8h x7-14 days.

New or Updated Treatment Guidelines

  • New clinical practice guidelines for the management of drug-resistant tuberculosis, from the American Thoracic Society, European Respiratory Society, Infectious Diseases Society of America, and Centers for Disease Control (Am J Respir Crit Care Med 2019;200:e93-e142). The guidelines are available on the journal website.
  • Guidelines for the diagnosis, treatment, and prevention of disseminated Mycobacterium chimaera infection following cardiac surgery with cardiopulmonary bypass, from the International Society of Cardiovascular Infectious Diseases (J Hosp Infect 2019 Nov 9 [Epub ahead of print]). The guidelines are available on the journal website.
  • In the recently published Committee Opinion (No. 782) on prevention of early-onset group B streptococcal disease in infants, the American College of Obstetricians and Gynecologists now recommends performing universal GBS screening between 36 0/7 and 37 6/7 weeks of gestation. All women whose vaginal-rectal cultures at 36 0/7-37 6/7 weeks of gestation are positive for GBS should receive appropriate intrapartum antibiotic prophylaxis unless a prelabor cesarean birth is performed in the setting of intact membranes (Obstet Gynecol 2019;134:e19). This Committee Opinion serves as an update to and replacement of the obstetric components of CDC’s 2010 GBS guidelines and is available on the ACOG website.

From CDC

  • The newly released Antibiotic Resistance Threats in the United States, 2019 (2019 AR Threats Report) is intended to serve as a reference for information on antibiotic resistance, provide the latest US antibiotic resistance burden estimates for human health, and highlight emerging areas of concern and additional action needed. The report divides 18 antibiotic-resistant bacteria and fungi into three categories based on level of concern to human health (urgent, serious, and concerning). Like the first AR Threat Report published in 2013, the 2019 report does not include viruses or parasites. It is available on the CDC website.
  • Guidance for using tafenoquine* for prevention and antirelapse therapy for malaria (MMWR Morb Mortal Wkly Rep 2019;68:1062). If G6PD status is unknown, quantitative G6PD testing must be performed to confirm normal activity before tafenoquine is used. See report for more details.
  • CDC maintains a list of multistate foodborne outbreak investigations since 2006 in which CDC was the lead public agency. Of recent interest are 1) 67 people from 19 states infected with E. coli O157:H7 linked to romaine lettuce harvested from the Salinas, California growing region, 2) 21 people from 13 states infected with Salmonella (serovar Oranienburg), likely due to contact with pet turtles (turtles carry Salmonella in their droppings), and 3) 241 people from 11 states with laboratory-confirmed Cyclospora infection, probably resulting from exposure (which occurred in five states) to fresh basil imported from Mexico. The Cyclospora outbreak appears to be over.

Drug Shortages (US)

  • Antimicrobial drugs or vaccines in reduced supply or unavailable (as of December 9, 2019) due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons:
    • [New on the list since November 8]: Erythromycin lactobionate injection, Sulfacetamide 10%/Prednisolone 0.2% ophthalmic ointment
    • [Shortage recently resolved]: Ceftriaxone injection, Ciprofloxacin oral suspension, Erythromycin 0.5% ophthalmic ointment, Nystatin oral suspension
    • [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, Cefuroxime injection
      • Clindamycin injection
      • Fluoroquinolones: Ciprofloxacin 0.3% ophthalmic solution, Gemifloxacin tablets
      • Glycopeptides, glycolipopeptides, lipopeptides: Daptomycin injection, Vancomycin injection
      • Macrolides/azalides: Azithromycin injection, Azithromycin ophthalmic solution 1% (unavailable)
      • Nitrofurantoin oral suspension
      • Nitroimidazoles: Metronidazole injection
      • Penicillins: Ampicillin/sulbactam injection, Piperacillin/tazobactam injection
      • Tetracyclines: Doxycycline hyclate injection
      • Topical (miscellaneous) antibacterials: Bacitracin ophthalmic ointment, Mupirocin calcium 2% cream, Mupirocin calcium 2% nasal ointment (unavailable), Sulfanilamide 15% vaginal cream (unavailable)
      • Antifungal drugs: Clotrimazole 10 mg oral troches, Fluconazole injection, Griseofulvin oral tablets and suspension
      • Antiparasitic drugs: Pentamidine isethionate
      • Antiretroviral drugs: None
      • Antiviral drugs: Acyclovir injection, Cidofovir injection, Letermovir injection (unavailable)
      • Vaccines: Hepatitis B vaccine recombinant, Rabies vaccine (and immune globulin), 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: 
    • Recent discontinuations: Interferon alfa-2b (Intron A, in October 2019), Quinidine gluconate IV (in December 2017), 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).

February 2019 Infectious Disease Update

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).

Antimicrobial Stewardship

  • 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)

March 2019 Infectious Disease Update

New or Updated Treatment Guidelines

  • Updated guidelines for the screening, diagnosis, prevention, and treatment of cytomegalovirus in organ transplant recipients, from the Infectious Diseases Community of Practice of the American Society of Transplantation (Clin Transplant 2019 Feb 28 [Epub ahead of print]).
  • Updated guidelines on potential drug-drug interactions between anti-infectives and immunosuppressants, from the Infectious Diseases Community of Practice of the American Society of Transplantation (Clin Transplant 2019 Feb 28 [Epub ahead of print]).
  • Updated guidelines for the diagnosis, prevention, and management of tuberculosis in the pre- and post-transplant period, from the Infectious Diseases Community of Practice of the American Society of Transplantation (Clin Transplant 2019 Feb 28 [Epub ahead of print]).
  • Updated guidelines for the diagnosis, prevention, and management of Nocardia infections after solid organ transplantation, from the Infectious Diseases Community of Practice of the American Society of Transplantation (Clin Transplant 2019 Feb 28 [Epub ahead of print]).
  • Updated guidelines for the diagnosis, prevention, and management of RNA respiratory viral infections in the pre- and post-transplant period, from the Infectious Diseases Community of Practice of the American Society of Transplantation (Clin Transplant 2019 Feb 28 [Epub ahead of print]).
  • Updated guidelines for the diagnosis, prevention, and management of viral hepatitis in the pre- and post-transplant period, from the Infectious Diseases Community of Practice of the American Society of Transplantation (Clin Transplant 2019 Feb 28 [Epub ahead of print]).

Drug Shortages (US)

  • Antimicrobial drugs or vaccines in reduced supply or unavailable (as of March 2, 2019) due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons:
    • [New on the list since February 17]: Erythromycin 0.5% ophthalmic ointment
    • [Shortage recently resolved]: Ciprofloxacin 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 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: Amphotericin B injection (unavailable), Fluconazole injection, Nystatin oral suspension (unavailable)
      • Antiparasitic drugs: Pentamidine isethionate
      • Antiviral drugs: Cidofovir injection (unavailable), Letermovir injection (unavailable), 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)

April 2019 Infectious Disease Update

Improved Sanford Guide Organization & Features

  • Web Edition* and mobile apps for Antimicrobial Therapy and Collection:
    • Activity Spectra tables may now be accessed from the main menu level on both the web edition and mobile app.
    • The Tables & Tools menu has been reorganized to correspond with the categories and structure found on drug pages.
    • new drug-drug interaction (DDI) table can be found in Tables & Tools under Drug Interactions.

New Drug Approvals

  • Dovato (dolutegravir 50 mg + lamivudine 300 mg), a two-drug fixed-dose regimen for the treatment of HIV-1 infection in adults who are ARV treatment-naive with no known or suspected resistance mutations to DTG or 3TC. Recommended dosage: one tablet once daily, with or without food.

New or Updated Treatment Guidelines

  • Guidelines on the optimization of beta-lactam treatment in ICU patients from The French Society of Pharmacology and Therapeutics (SFPT) and the French Society of Anaesthesia and Intensive Care Medicine (SFAR) (Crit Care 23:104, 2019). The guidelines are available on the journal website.
  • Guidelines for empiric and targeted antimicrobial therapy of complicated intra-abdominal infections (cIAI) from the 2018 Lebanese Society of Infectious Diseases and Clinical Microbiology (BMC Infect Dis 19:293, 2019). The guidelines are availalbe on the journal website.
  • Updated clinical guidelines for the diagnosis and treatment of HIV/AIDS in HIV-Infected Koreans from the Committee for Clinical Guidelines for the Diagnosis and Treatment of HIV/AIDS of the Korean Society for AIDS (Infect Chemother 51:77, 2019). These guidelines update the 2015 version are are available on the journal website.
  • Clinical management guidelines for the management of acute appendicitis in adults from the Eastern Association for the Surgery of Trauma (J Trauma Acute Care Surg 2019 Mar 22 [Epub ahead of print]).
  • Updated guidelines for the diagnosis, prevention and management of blastomycosis, histoplasmosis and coccidioidomycosis in the pre- and post-transplant period from the Infectious Diseases Community of Practice of the American Society of Transplantation (Clin Transplant 2019 Mar 29 [Epub ahead of print]).
  • Updated guidelines for the management of vancomycin-resistant enterococci (VRE) infections in solid organ transplant candidates and recipients from the Infectious Diseases Community of Practice of the American Society of Transplantation (Clin Transplant 2019 Mar 26 [Epub ahead of print]).
  • Updated guidelines for the diagnosis, prevention and management of diarrhea in the pre- and post-transplant period from the Infectious Diseases Community of Practice of the American Society of Transplantation (Clin Transplant 2019 Mar 26 [Epub ahead of print]).
  • Updated clinical practice guidelines for the management of asymptomatic bacteriuria from the Infectious Diseases Society of America (Clin Infect Dis 2019 Mar 21 [Epub ahead of print]). These guidelines update the 2005 version and are available on the IDSA website.
  • Updated guidelines for the management of Clostridioides (Clostridium) difficile infection in surgical patients from the World Society of Emergency Surgery (World J Emerg Surg 14:8, 2019). These guidelines update the 2015 version and are available on the journal website.
  • Position statement on the management of hepatitis C virus infection in patients with chronic kidney disease from a joint committee of the Italian Association for the Study of the Liver (AISF), Italian Society of Internal Medicine (SIMI), Italian Society of Infectious and Tropical Disease (SIMIT), and the Italian Society of Nephrology (SIN) (Infection 47:141, 2019).
  • Updated guidelines for the management of sepsis in neutropenic cancer patients from the Infectious Diseases Working Party (AGIHO) and Intensive Care Working Party (iCHOP) of the German Society of Hematology and Medical Oncology (DGHO) (Ann Hematol 2019 Feb 22 [Epub ahead of print]). The guidelines update the 2013 version and are available on the journal website.
  • Guidelines for the treatment and management of women living with HIV in the UK during pregnancy and postpartum, and their infants, from the British HIV Association (HIV Med 20 Suppl 3:s2, 2019). The guidelines are available on the journal website.
  • Clinical practice guidelines for the provision, monitoring and support of pre-exposure prophylaxis (PrEP) for the prevention of
    HIV acquisition from the British HIV Association and the British Association for Sexual Health and HIV (HIV Med 20 Suppl 2:s2, 2019). The guidelines are available on the journal website.
  • Updated guidelines for the diagnosis, prevention and management of cryptococcosis in the pre- and post-transplant period from the Infectious Diseases Community of Practice of the American Society of Transplantation (Clin Transplant 2019 Mar 22 [Epub ahead of print]).
  • Updated guidelines for the epidemiology, diagnosis, and management of Aspergillus in solid organ transplant recipients from the Infectious Diseases Community of Practice of the American Society of Transplantation (Clin Transplant 2019 Mar 21 [Epub ahead of print]).
  • Updated guidelines for the diagnosis, prevention and management of tissue and blood protozoal infections in the pre- and post-transplant period from the Infectious Diseases Community of Practice of the American Society of Transplantation (Clin Transplant 2019 Mar 21 [Epub ahead of print]).
  • Updated guidelines for the diagnosis and management of pneumonia in the post-transplant period from the Infectious Diseases Community of Practice of the American Society of Transplantation (Clin Transplant 2019 Mar 21 [Epub ahead of print]).
  • Updated guidelines for the diagnosis, prevention, and management of adenovirus infection after solid organ transplantation from the Infectious Diseases Community of Practice of the American Society of Transplantation (Clin Transplant 2019 Mar 12 [Epub ahead of print]).
  • Updated guidelines on BK polyomavirus infection, replication, and disease from the Infectious Diseases Community of Practice of the American Society of Transplantation (Clin Transplant 2019 Mar 12 [Epub ahead of print]).
  • Updated guidelines for the epidemiology, diagnosis, and management of emerging fungal infections in solid organ transplant recipients from the Infectious Diseases Community of Practice of the American Society of Transplantation (Clin Transplant 2019 Mar 12 [Epub ahead of print]).
  • Updated guidelines for the diagnosis, prevention, and management of herpes simplex virus infection in the pre- and post-transplant period from the Infectious Diseases Community of Practice of the American Society of Transplantation (Clin Transplant 2019 Mar 12 [Epub ahead of print]).
  • Updated guidelines for the diagnosis, prevention, and management of HHV-6A, HHV-6B, HHV-7, and HHV-8 in the pre- and post-transplant period from the Infectious Diseases Community of Practice of the American Society of Transplantation (Clin Transplant 2019 Mar 7 [Epub ahead of print]).
  • Updated guidelines for the screening, diagnosis, prevention, and treatment of cytomegalovirus in organ transplant recipients, from the Infectious Diseases Community of Practice of the American Society of Transplantation (Clin Transplant 2019 Feb 28 [Epub ahead of print]).
  • Updated guidelines on potential drug-drug interactions between anti-infectives and immunosuppressants, from the Infectious Diseases Community of Practice of the American Society of Transplantation (Clin Transplant 2019 Feb 28 [Epub ahead of print]).
  • Updated guidelines for the diagnosis, prevention, and management of tuberculosis in the pre- and post-transplant period, from the Infectious Diseases Community of Practice of the American Society of Transplantation (Clin Transplant 2019 Feb 28 [Epub ahead of print]).
  • Updated guidelines for the diagnosis, prevention, and management of Nocardia infections after solid organ transplantation, from the Infectious Diseases Community of Practice of the American Society of Transplantation (Clin Transplant 2019 Feb 28 [Epub ahead of print]).
  • Updated guidelines for the diagnosis, prevention, and management of RNA respiratory viral infections in the pre- and post-transplant period, from the Infectious Diseases Community of Practice of the American Society of Transplantation (Clin Transplant 2019 Feb 28 [Epub ahead of print]).

From CDC

  • Now that IV quinidine has been discontinued by the manufacturer and is no longer available, artesunate (the WHO-recommended first-line treatment) is now first-line treatment for severe malaria in the US. IV artesunate is neither FDA-approved nor commercially available in the US, but it has been available from CDC since 2007. For details on how to obtain IV artesunate and other FAQs a Malaria Notice has been posted.

Weekly Practice Pearls

  • In resource-limited countries, prolonged treatment courses of amphotericin B for infections such as cryptococcal meningitis in patients with HIV can be challenging to administer safely and effectively. In a phase 2 noninferiority trial conducted in Tanzania and Botswana, induction therapy with a single dose of liposomal amphotericin B (10 mg/kg) in combination with high-dose oral fluconazole (1200 mg daily for 2 weeks) was well tolerated and found to be noninferior to 2 weeks of once-daily liposomal amphotericin B (3 mg/kg) plus oral fluconazole for the primary outcome measure of mean rate of fungal clearance from the CSF. This short-course treatment strategy is now being studied in a phase 3 clinical endoint trial (Clin Infect Dis 68:393, 2019).

Drug Shortages (US)

  • Antimicrobial drugs or vaccines in reduced supply or unavailable (as of April 7, 2019) due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons:
    • [New on the list since March 31]: None
    • [Shortage recently resolved]: Ciprofloxacin 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 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
      • Other antibacterials: Clindamycin injection, Metronidazole injection, Mupirocin calcium 2% cream, Mupirocin calcium 2% nasal ointment (unavailable), Nitrofurantoin oral suspension
      • Antifungal drugs: Amphotericin B injection (unavailable), Clotrimazole 10 mg oral troches, Fluconazole injection, Nystatin oral suspension (unavailable)
      • Antiparasitic drugs: Pentamidine isethionate
      • Antiretroviral drugs: Nelfinavir tablets (unavailable)
      • Antiviral drugs: Cidofovir injection (unavailable), Letermovir injection (unavailable), 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)

May 2019 Infectious Disease Update

New Print Editions Now Available

New Drug Approvals

  • Avaclyr (acyclovir* 3% ophthalmic ointment), approved for the treatment of acute herpetic keratitis (dendritic ulcers) in patients with HSV-1 and HSV-2. Recommended dosage: one ribbon of ointment in the lower cul-de-sac of the affected eye 5 times a day until ulcer has healed, then 3 times daily for 7 days. Product availability: 3.5 gm tubes.
  • Dengvaxia (Dengue Tetravalent Vaccine, Live), approved by the US FDA for the prevention of dengue disease caused by all dengue virus serotypes (1, 2, 3, and 4). There are major restrictions: the vaccine is approved only for use in individuals age 9-16 with laboratory-confirmed previous dengue infection and living in endemic areas. It is a live, attenuated vaccine that is administered as three separate injections six months apart. The vaccine has already been approved in 19 countries and the European Union.
  • Tolsura (itraconazole*), approved for the treatment of blastomycosis (pulmonary and extrapulmonary), histoplasmosis (including chronic cavitary pulmonary disease and disseminated, non-meningeal histoplasmosis), and aspergillosis (pulmonary and extrapulmonary) in patients who are intolerant of or who are refractory to amphotericin B*. This product is a new formulation with improved bioavailability. Availability: 65 mg capsules.

Updated Pediatric HIV Guidelines

  • Updated Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection from the HHS Panel on Antiretroviral Therapy and Medical Management of Children Living with HIV are available on the AIDSinfo website.

New or Updated Treatment Guidelines

  • Updated guidelines for the epidemiology, diagnosis, prevention, and management of infection due to Arenaviruses and West Nile Virus (WNV) in the pre- and post-transplant period, from the Infectious Diseases Community of Practice of the American Society of Transplantation (Clin Transplant 2019 Apr 25 [Epub ahead of print]).
  • Updated guidelines for the diagnosis, prevention and management of Human T-cell lymphotrophic virus 1 (HTLV)-1 in the pre- and post-transplant period, from the Infectious Diseases Community of Practice of the American Society of Transplantation (Clin Transplant 2019 Apr 25 [Epub ahead of print]).
  • Updated guidelines for the prevention and management of Clostridium difficile infection in solid organ transplant (SOT) recipients from the Infectious Diseases Community of Practice of the American Society of Transplantation (Clin Transplant 2019 Apr 19 [Epub ahead of print]).
  • Updated guidelines for the vaccination of solid organ transplant candidates and recipients from the Infectious Diseases Community of Practice of the American Society of Transplantation (Clin Transplant 2019 Apr 19 [Epub ahead of print]).

Practice Pearls

  • Eculizumab is a monoclonal antibody that binds to complement protein C5, inhibiting its cleavage to C5a and C5b and thereby inhibiting deployment of the terminal complement system. It is indicated for paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, and anti-acetylcholine receptor antibody-positive generalized myasthenia gravis. Unfortunately, complement blockade at C5 interferes with the immune system’s ability to respond effectively to Neisseria infection. Therapy with eculizumab is thought to increase the risk of meningococcal disease 1000- to 2000-fold. The product labeling includes a black box warning about life-threatening and fatal infection due to N. meningitidis*, but infection due to other Neisseria species is less well characterized. The first case series of N. gonorrhoeae* infections in patients receiving eculizumab was recently published. Eight of nine cases of N. gonorrhoeae infection identified by an FDA spontaneous safety report search were disseminated gonococcal infection (DGI). All eight DGI patients were hospitalized, seven were bacteremic, and two required pressor support (one of whom also required mechanical ventilation). The limited data suggest that patients treated with eculizumab may be at higher risk of DGI than the general population (Clin Infect Dis 2018 Nov 12 [Epub ahead of print]).

Drug Shortages (US)

  • Antimicrobial drugs or vaccines in reduced supply or unavailable (as of May 4, 2019) due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons:
    • [New on the list since April 21]: Doxycycline injection
    • [Shortage recently resolved]: Ciprofloxacin 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 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
      • Other antibacterials: Clindamycin injection, Metronidazole injection, Mupirocin calcium 2% cream, Mupirocin calcium 2% nasal ointment (unavailable), Nitrofurantoin oral suspension
      • Antifungal drugs: Amphotericin B injection (unavailable), Clotrimazole 10 mg oral troches, Fluconazole injection, Nystatin oral suspension (unavailable)
      • Antiparasitic drugs: Pentamidine isethionate
      • Antiretroviral drugs: Nelfinavir tablets
      • Antiviral drugs: Cidofovir injection (unavailable), Letermovir injection (unavailable), 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

June 2019 Infectious Disease Update

CDC Health Advisory

  • CDC is expecting a 3 to 10 month nationwide shortage of Aplisol (Par Pharmaceuticals), one of two purified-protein derivative (PPD) tuberculin antigens that are licensed by the US FDA for use in performing tuberculin skin tests (TSTs). The time frame is the manufacturer’s current estimate and is subject to change. Suggested approaches for dealing with the shortage include substituting IGRA blood tests for TSTs, using the other licensed product (Tubersol), and prioritizing allocation of TSTs in consultation with state and local public health authorities. Further information can be found on the CDC website.

Practice Pearls

  • Kounis syndrome, first described in 1991, is an unusual hypersensitivity reaction to various allergens, including drugs, that results in vasospasm of the coronary arteries. It is also known as allergic angina or allergic MI. There are three types. In type I, patients have normal coronary arteries, no predisposing factors, and no elevation in cardiac enzymes. Type II occurs in patients with inactive underlying coronary artery disease in whom the allergic episode results in vasospasm without cardiac enzyme elevation. Type III includes coronary artery stent thrombosis secondary to the allergic episode. Kounis syndrome manifests with signs and symptoms of myocardial ischemia and is potentially life-threatening if not recognized promptly. Treatment begins with discontinuation of the causative agent, but there is no consensus as to the value of administering drugs that dilate the coronary arteries or suppress the allergic response. Many case reports of Kounis syndrome associated with beta-lactams, most commonlyamoxicillin, have been published. A recent report describing type I Kounis syndrome in a patient receiving a preoperative dose of vancomycin for surgical management of a gangrenous toe is only the second to implicate that drug (Am J Emerg Med 2019 June 3 [Epub ahead of print]).

New or Updated Treatment Guidelines

  • Guidelines for the diagnosis and management of CMV infection in patients following hematopoietic stem-cell transplantation and in patients receiving other types of therapy for hematological malignancies, from the 2017 European Conference on Infectious in Leukemia (ECIL 7) (Lancet Infect Dis 2019 May 29 [Epub ahead of print]).
  • 2019 guidelines for the management of tuberculosis in adults living with HIV, from the British HIV Association (HIV Med 20 Suppl 6: s2-s83, 2019). These guidelines update the 2011 version and are available on the journal website.
  • Guidelines from the French scientific societies for the biological diagnosis, treatment, persistent symptoms after documented or suspected Lyme borreliosis (Med Mal Infect 2019 May 30 [Epub ahead of print]).
  • Updated guidelines for the diagnosis, prevention and management of varicella zoster virus (VZV) in the pre- and post-transplant period, from the Infectious Diseases Community of Practice of the American Society of Transplantation (Clin Transplant 2019 June 4 [Epub ahead of print]).
  • Updated guidelines for the diagnosis and management of Candida infections in solid organ transplant recipients, from the Infectious Diseases Community of Practice of the American Society of Transplantation (Clin Transplant 2019 June 2 [Epub ahead of print]).
  • Updated guidelines for the diagnosis, prevention, and management of intestinal parasites in the pre- and post-transplant period, from the Infectious Diseases Community of Practice of the American Society of Transplantation (Clin Transplant 2019 May 30 [Epub ahead of print]).
  • Updated guidelines for the epidemiology, diagnosis, prevention and management of methicillin-resistant Staphylococcus aureus (MRSA) infections in solid organ transplantation, from the Infectious Diseases Community of Practice of the American Society of Transplantation (Clin Transplant 2019 May 23 [Epub ahead of print]).
  • Updated guidelines for the management of intra-abdominal infections in solid organ transplant recipients, from the Infectious Diseases Community of Practice of the American Society of Transplantation (Clin Transplant 2019 May 18 [Epub ahead of print]).
  • Updated guidelines for the diagnosis, prevention, and management of infections due to multidrug-resistant (MDR) Gram-negative bacilli in the pre- and post-transplant period, from the Infectious Diseases Community of Practice of the American Society of Transplantation (Clin Transplant 2019 May 18 [Epub ahead of print]).
  • Updated guidelines for the epidemiology and management of human papillomavirus (HPV) infections in solid organ transplant recipients, from the Infectious Diseases Community of Practice of the American Society of Transplantation (Clin Transplant 2019 May 11 [Epub ahead of print]).
  • Updated guidelines for the epidemiology, diagnosis, prevention and management of nontuberculous mycobacterial infections in the pre- and post-transplant period, from the Infectious Diseases Community of Practice of the American Society of Transplantation (Clin Transplant 2019 May 11 [Epub ahead of print]).
  • Updated guidelines for the diagnosis, prevention and management of Pneumocystis jiroveci fungal infection in solid organ transplant recipients, from the Infectious Diseases Community of Practice of the American Society of Transplantation (Clin Transplant 2019 May 11 [Epub ahead of print]).
  • Updated guidelines for the diagnosis, prevention, and management of post-operative surgical site infectionsin solid organ transplantation, from the Infectious Diseases Community of Practice of the American Society of Transplantation (Clin Transplant 2019 May 11 [Epub ahead of print]).

Drug Shortages (US)

  • Antimicrobial drugs or vaccines in reduced supply or unavailable (as of June 11, 2019) due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons:
    • [New on the list since May 4]: Sulfanilamide 15% vaginal cream 
    • [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
      • 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

July 2019 Infectious Disease Update

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

August 2019 Infectious Disease Update

From CDC

  • Updated recommendations from the CDC Advisory Committee on Immunization Practices (ACIP) regarding prevention of Japanese encephalitis (JE) among US travelers and laboratory workers (MMWR Recomm Rep 2019;68(No. RR-2):1-33). The report summarizes the epidemiology of JE, describes the JE vaccine that is licensed and available in the US, and provides recommendations for its use. These recommendations update the 2010 release and are available on the CDC website.

Practice Pearls

  • Sofosbuvir/velpatasvir (Epclusa) is a pangenotypic, fixed-dose combination of sofosbuvir (NS5B RNA polymerase inhibitor) and velpatasvir (NS5A inhibitor) used for the treatment of chronic HCV. Velpatasvir is a lipophilic weak base with pH-dependent solubility (its solubility decreases as pH increases). Therefore, drugs like proton-pump inhibitors (PPI) impair velpatasvir absorption by raising gastric pH, and coadministration of sofosbuvir/velpatasvir with PPIs is generally not recommended. If it is medically necessary, the manufacturer recommends that sofosbuvir/velpatasvir be administered with food and taken four hours before omeprazole (20 mg). In a recent open-label, randomized, 3-arm crossover study, 11 healthy volunteers were administered a single dose of sofosbuvir/velpatasvir a) alone, b) with omeprazole (at steady-state concentrations), or c) with omeprazole combined with 250 mL of Coca-Cola. Pharmacokinetic sampling was performed on days 5-7 of each arm (see chart below). The data suggest that taking sofosbuvir/velpatasvir with Coca-Cola can overcome the interaction with proton-pump inhibitors, presumably by temporarily lowering gastric pH and thus enhancing velpatasvir solubility and absorption (Clin Pharmacol Ther 2019 Jul 17 [Epub ahead of print]).
    Study arm (seven days per arm, 7 days washout between arms) Velpatasvir AUC
    (geometric mean)
    Sofosbuvir/velpatasvir 400/100 mg on day 5 + 250 mL water 3742 mcg*hr/L
    Sofosbuvir/velpastavir 400/100 mg on day 5 + 250 mL water, omeprazole 40 mg qd (days 1-6) 2705 mcg*hr/L
    Sofosbuvir/velpastavir 400/100 mg on day 5 + 250 mL Coca-Cola, omeprazole 40 mg qd (days 1-6) 5981 mcg*hr/L

 

Drug Shortages (US)

  • Antimicrobial drugs or vaccines in reduced supply or unavailable (as of August 1, 2019) due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons:
    • [New on the list since July 17]: Bacitracin ophthalmic ointment, Griseofulvin oral tablets, Letermovir tablets
    • [Shortage recently resolved]: Amphotericin B injection, Nelfinavir tablets, Valganciclovir oral powder for solution
    • [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
      • Clindamycin 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, Erythromycin 0.5% ophthalmic ointment
      • Nitrofurantoin oral suspension
      • Nitroimidazoles: Metronidazole injection
      • Penicillins: Ampicillin/sulbactam injection, Piperacillin/tazobactam injection
      • Tetracyclines: Doxycycline hyclate injection
      • Topical (miscellaneous) antibacterials: Mupirocin calcium 2% cream, Mupirocin calcium 2% nasal ointment (unavailable), 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)
      • 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

September 2019 Infectious Disease Update

New Antimicrobial Drug Approvals

  • Xenleta (lefamulin*), a systemically-administered pleuromutilin, approved for the treatment of adult with community-acquired pneumonia caused by susceptible strains of S. pneumoniae, MSSA, H. influenzae, L. pneumophila, M. pneumoniae, and C. pneumoniae. Pleuromutilins inhibit bacterial protein synthesis by binding to the peptidyl transferase center of the 50S bacterial ribosome, thereby preventing the binding of tRNA for peptide transfer. Recommended dosage: 150 mg IV q12h x5-7 days (switching to oral therapy to complete the course if appropriate), or 600 mg po q12h x5 days. Product availability: injection, 600 mg tablets.
  • Pretomanid* Tablets, a nitroimidazooxazine antimycobacterial drug, approved as part of a combination regimen with bedaquiline and linezolid for the treatment of adults with pulmonary MDR-TB or XDR-TB. Recommended dosage: 200 mg po once daily for 26 weeks (with bedaquiline and linezolid). The combination regimen should be taken with food. Product availability: 200 mg tablets.

Drug Safety Communications

  • The US FDA has issued a warning about worsening liver function or liver failure occurring in chronic hepatitis C patients with moderate to severe liver impairment who are treated with glecaprevir/pibrentasvir (Mavyret), elbasvir/grazoprevir (Zepatier), or sofosbuvir/velpatasvir/voxilaprevir (Vosevi). All three contain a NS3/4A protease inhibitor (the drug ending in -previr) and are not indicated for use in patients with moderate to severe liver impairment.  In most patients, symptoms resolved or new-onset worsening of liver function improved after stopping treatment. The full Drug Safety Communication can be found here.

From CDC

  • The recommendations of the Advisory Committee on Immunization Practices (ACIP) concerning the use of seasonal influenza vaccines in the US for the 2019-2020 season have been released (MMWR Recomm Rep 2019;68(No. RR-3):1–21). U.S. trivalent vaccines will contain hemagglutinin (HA) derived from an A/Brisbane/02/2018 (H1N1)pdm09–like virus, an A/Kansas/14/2017 (H3N2)–like virus, and a B/Colorado/06/2017–like virus (Victoria lineage). Quadrivalent influenza vaccines will contain HA derived from these three viruses and from an additional influenza B vaccine virus, a B/Phuket/3073/2013–like virus (Yamagata lineage). This composition includes updates in the influenza A(H1N1)pdm09 and influenza A(H3N2) components of the vaccine. The full report is available on the MMWR website.

New or Updated Treatment Guidelines

  • Clinical practice guidelines for microbiological laboratory testing used in the diagnosis of fungal infections commonly encountered in pulmonary and critical care practice, from the American Thoracic Society (Am J Respir Crit Care Med 2019;200:535). The guidelines are available for download on the journal website.
  • Revised guidelines for the management of HHV-6 infections in patients with hematological malignancies and after hematopoietic stem cell transplantation, from the 2017 European Conference on Infectious in Leukemia (Haematologica 2019 August 29 [Epub ahead of print]). The guidelines are available for download on the journal website.

Drug Shortages (US)

  • Antimicrobial drugs or vaccines in reduced supply or unavailable (as of August 30, 2019) due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons:
    • [New on the list since August 1]: None
    • [Shortage recently resolved]: Hepatitis A vaccine inactivated, Letermovir 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
      • Clindamycin 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, Erythromycin 0.5% ophthalmic ointment
      • Nitrofurantoin oral suspension
      • Nitroimidazoles: Metronidazole injection
      • Penicillins: Ampicillin/sulbactam injection, Piperacillin/tazobactam injection
      • Tetracyclines: Doxycycline hyclate injection
      • Topical (miscellaneous) antibacterials: Bacitracin ophthalmic ointment (unavailable), Mupirocin calcium 2% cream, Mupirocin calcium 2% nasal ointment (unavailable), Sulfanilamide 15% vaginal cream (unavailable)
      • Antifungal drugs: Clotrimazole 10 mg oral troches, Fluconazole injection, Griseofulvin oral tablets, Nystatin oral suspension
      • Antiparasitic drugs: Pentamidine isethionate
      • Antiretroviral drugs: None
      • Antiviral drugs: Cidofovir injection, Letermovir injection (unavailable)
      • Vaccines: 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)

October 2019 Infectious Disease Update

New or Updated Treatment Guidelines

Improved Access to IV Artesunate

  • IV artesunate* is the first-line, WHO-recommended treatment for severe malaria but is neither FDA-approved nor commercially available in the United States. Obtaining the drug from CDC has been problematic due to limited supply and other issues, but recent efforts have improved drug accessibility for those who need it. As of April 2019, CDC will release artesunate for all cases of severe malaria, any case of malaria where the patient is not tolerating oral medications, or any highly suspected case of severe malaria. The drug is pre-positioned at 18 locations nationally, and the hospital will need to send someone to the receiving airport or quarantine station to retrieve it. Call the CDC Malaria Hotline, (770) 488-7788, Mon-Fri, 9 am to 5 pm US EST. After hours, or on weekends or holidays, call the CDC Emergency Operations Center at (770) 488-7100 and ask to page the person on call for the Malaria Branch.

Practice Pearl

  • DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) is a T-cell-mediated hypersensitivity reaction characterized by fever, facial edema, maculopapular rash, lymphadenopathy, eosinophilia, mononucleosis-like atypical lymphocytosis, and multiorgan involvement (hepatitis, nephritis, arthritis, pneumonitis, carditis). The latency period is 2-8 weeks, and mortality approaches 10%. Recognized drug triggers include anticonvulsants, allopurinol, and antibiotics, including vancomycin. There are well-known HLA associations with drug hypersensitivity reactions, such as HLA-B*57:01 and hypersensitivity to abacavir; could variation within HLA predispose to vancomycin-associated DRESS? In 23 patients with vancomycin-associated DRESS, 82.6% carried the HLA-A*32:01 allele compared to 0% of 46 matched vancomycin-tolerant control patients (p=1 x 10-8). The patients with vancomycin-associated DRESS were primarily of European ancestry. In a larger cohort of 54,249 patients, the HLA-A*32:01 allele carriage rate was 6.3%, matching the carriage rate in other cohorts of mainly European ancestry. The authors estimate that approximately 75 patients started on vancomycin would need to undergo HLA-A*32:01 testing to prevent one case of vancomycin-associated DRESS. If validated, the association of HLA-A*32:01 carriage with vancomycin-associated DRESS could be useful not only for the prediction and prevention of the hypersensitivity reaction, but also for monitoring and risk stratification (J Allergy Clin Immunol 2019;144:183).

Drug Shortages (US)

  • Antimicrobial drugs or vaccines in reduced supply or unavailable (as of October 7, 2019) due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons:
    • [New on the list since August 30]: Acyclovir injection, Rabies Immune Globulin, Rabies vaccine
    • [Shortage recently resolved]: Erythromycin lactobionate 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
      • Clindamycin 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 0.5% ophthalmic ointment
      • Nitrofurantoin oral suspension
      • Nitroimidazoles: Metronidazole injection
      • Penicillins: Ampicillin/sulbactam injection, Piperacillin/tazobactam injection
      • Tetracyclines: Doxycycline hyclate injection
      • Topical (miscellaneous) antibacterials: Bacitracin ophthalmic ointment (unavailable), Mupirocin calcium 2% cream, Mupirocin calcium 2% nasal ointment (unavailable), Sulfanilamide 15% vaginal cream (unavailable)
      • Antifungal drugs: Clotrimazole 10 mg oral troches, Fluconazole injection, Griseofulvin oral tablets, Nystatin oral suspension
      • Antiparasitic drugs: Pentamidine isethionate
      • Antiretroviral drugs: None
      • Antiviral drugs: Cidofovir injection, Letermovir injection (unavailable)
      • Vaccines: 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)

November 2019 Infectious Disease Update

New or Updated Treatment Guidelines

New for H. pylori Treatment

  • The US FDA has approved the three-drug combination of rifabutin, amoxicillin, and omeprazole (Talicia*) for the treatment of Helicobacter pyloriinfection in adults. Each capsule contains rifabutin 12.5 mg (immediate-release), amoxicillin 250 mg (immediate-release), and omeprazole 10 mg (delayed-release). Recommended dosage is four capsules q8h for 14 days, with food. US product launch is expected in the first quarter of 2020.

Intron A Discontinued

  • Based on an evaluation of clinical use and the availability of alternative therapies, Merck is discontinuing recombinant interferon alfa-2b (Intron A), in all strengths. Supply availability should continue over the next 1-2 years depending on product formulation and dose strength.

CABP Indication for Delafloxacin

  • Delafloxacin* is now indicated in adults for the treatment of community-acquired bacterial pneumonia due to S. pneumoniae, MSSA, K. pneumoniae, E. coli, P. aeruginosa, H. influenzae, H. parainfluenzae, C. pneumoniae, L. pneumophila, and M. pneumoniae. This is the drug’s second FDA-approved indication.

Baloxavir Indication Expanded to High-Risk Patients

  • Baloxavir* is now indicated for the treatment of acute uncomplicated influenza in patients 12 years of age and older who have been symptomatic for ≤48 hours and are 1) otherwise healthy, or 2) at high risk of developing influenza-related complications. High risk factors include underlying asthma or chronic lung disease, diabetes, heart disease, morbid obesity, and age ≥65 years.

Second Drug Approved for PrEP

  • Descovy (emtricitabine 200 mg + TAF 25 mg) is the second drug to be approved by the US FDA for HIV-1 pre-exposure prophylaxis (PrEP)*. It is indicated in at-risk adults and adolescents weighing at least 35 kg to reduce the risk of HIV-1 infection from sexual acquisition, excluding individuals at risk from receptive vaginal sex. Individuals must be screened for HIV-1 infection immediately prior to starting PrEP, and then at least once every three months. The recommended dosage is one tablet orally once daily, with or without food. The first drug to be approved for PrEP was Truvada (emtricitabine 200 mg + TDF 300 mg) in 2012.

Drug Shortages (US)

  • Antimicrobial drugs or vaccines in reduced supply or unavailable (as of November 8, 2019) due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons:
    • [New on the list since October 17]: None
    • [Shortage recently resolved]: Erythromycin lactobionate 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
      • Clindamycin injection
      • Fluoroquinolones: Ciprofloxacin 0.3% ophthalmic solution, Ciprofloxacin oral suspension, Gemifloxacin tablets
      • Glycopeptides, glycolipopeptides, lipopeptides: Daptomycin injection, Vancomycin injection
      • Macrolides/azalides: Azithromycin injection, Azithromycin ophthalmic solution 1% (unavailable), Erythromycin 0.5% ophthalmic ointment
      • Nitrofurantoin oral suspension
      • Nitroimidazoles: Metronidazole injection
      • Penicillins: Ampicillin/sulbactam injection, Piperacillin/tazobactam injection
      • Tetracyclines: Doxycycline hyclate injection
      • Topical (miscellaneous) antibacterials: Bacitracin ophthalmic ointment (unavailable), Mupirocin calcium 2% cream, Mupirocin calcium 2% nasal ointment (unavailable), Sulfanilamide 15% vaginal cream (unavailable)
      • Antifungal drugs: Clotrimazole 10 mg oral troches, Fluconazole injection, Griseofulvin oral tablets and suspension, Nystatin oral suspension
      • Antiparasitic drugs: Pentamidine isethionate
      • Antiretroviral drugs: None
      • Antiviral drugs: Acyclovir injection, Cidofovir injection, Letermovir injection (unavailable)
      • Vaccines: Hepatitis B vaccine recombinant, Rabies vaccine (and immune globulin), 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: 
    • Recent discontinuations: Interferon alfa-2b (Intron A, in October 2019), Quinidine gluconate IV (in December 2017), 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

December 2019 Infectious Disease Update

Sanford Guide Releases New Apps

  • Sanford Guide recently upgraded its systems to support a new generation of mobile apps. Users of the Sanford Guide Collection app will see many improvements immediately, while users of other Sanford Guide apps will see new features become available in the next few months. Among the new features now available to Collection users:
    • Clean and modern look and feel with intuitive user interface and improved visual cues to accelerate navigation.
    • Cloud-based bookmarks and notes are shared between platforms (create a bookmark on one device and it will appear automatically on your other devices).
    • The Spectra of Activity is faster on most devices, and when examining an interaction by tapping on it, Stewardship Assist users can choose to filter down to only the active data set or to view all data sets at once.
    • Stewardship Assist users can now access institutional data by tapping their hospital’s logo on the home screen.

New Parenteral Cephalosporin

  • The US FDA has approved cefiderocol* (Fetroja) for the treatment of adults with complicated UTI, including pyelonephritis*, caused by susceptible strains of E. coli, K. pneumoniae, P. mirabilis, P. aeruginosa, and E. cloacae complex. Cefiderocol functions as a siderophore, chelating ferric ions and taking advantage of the bacterial iron transport system for enhanced accumulation in the bacterial periplasmic space. The drug should be reserved for use in patients with limited or no alternative treatment options. Recommended dosage: 2 gm IV (infused over 3 hours) q8h x7-14 days.

New or Updated Treatment Guidelines

  • New clinical practice guidelines for the management of drug-resistant tuberculosis, from the American Thoracic Society, European Respiratory Society, Infectious Diseases Society of America, and Centers for Disease Control (Am J Respir Crit Care Med 2019;200:e93-e142). The guidelines are available on the journal website.
  • Guidelines for the diagnosis, treatment, and prevention of disseminated Mycobacterium chimaera infection following cardiac surgery with cardiopulmonary bypass, from the International Society of Cardiovascular Infectious Diseases (J Hosp Infect 2019 Nov 9 [Epub ahead of print]). The guidelines are available on the journal website.
  • In the recently published Committee Opinion (No. 782) on prevention of early-onset group B streptococcal disease in infants, the American College of Obstetricians and Gynecologists now recommends performing universal GBS screening between 36 0/7 and 37 6/7 weeks of gestation. All women whose vaginal-rectal cultures at 36 0/7-37 6/7 weeks of gestation are positive for GBS should receive appropriate intrapartum antibiotic prophylaxis unless a prelabor cesarean birth is performed in the setting of intact membranes (Obstet Gynecol 2019;134:e19). This Committee Opinion serves as an update to and replacement of the obstetric components of CDC’s 2010 GBS guidelines and is available on the ACOG website.

From CDC

  • The newly released Antibiotic Resistance Threats in the United States, 2019 (2019 AR Threats Report) is intended to serve as a reference for information on antibiotic resistance, provide the latest US antibiotic resistance burden estimates for human health, and highlight emerging areas of concern and additional action needed. The report divides 18 antibiotic-resistant bacteria and fungi into three categories based on level of concern to human health (urgent, serious, and concerning). Like the first AR Threat Report published in 2013, the 2019 report does not include viruses or parasites. It is available on the CDC website.
  • Guidance for using tafenoquine* for prevention and antirelapse therapy for malaria (MMWR Morb Mortal Wkly Rep 2019;68:1062). If G6PD status is unknown, quantitative G6PD testing must be performed to confirm normal activity before tafenoquine is used. See report for more details.
  • CDC maintains a list of multistate foodborne outbreak investigations since 2006 in which CDC was the lead public agency. Of recent interest are 1) 67 people from 19 states infected with E. coli O157:H7 linked to romaine lettuce harvested from the Salinas, California growing region, 2) 21 people from 13 states infected with Salmonella (serovar Oranienburg), likely due to contact with pet turtles (turtles carry Salmonella in their droppings), and 3) 241 people from 11 states with laboratory-confirmed Cyclospora infection, probably resulting from exposure (which occurred in five states) to fresh basil imported from Mexico. The Cyclospora outbreak appears to be over.

Drug Shortages (US)

  • Antimicrobial drugs or vaccines in reduced supply or unavailable (as of December 9, 2019) due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons:
    • [New on the list since November 8]: Erythromycin lactobionate injection, Sulfacetamide 10%/Prednisolone 0.2% ophthalmic ointment
    • [Shortage recently resolved]: Ceftriaxone injection, Ciprofloxacin oral suspension, Erythromycin 0.5% ophthalmic ointment, Nystatin oral suspension
    • [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, Cefuroxime injection
      • Clindamycin injection
      • Fluoroquinolones: Ciprofloxacin 0.3% ophthalmic solution, Gemifloxacin tablets
      • Glycopeptides, glycolipopeptides, lipopeptides: Daptomycin injection, Vancomycin injection
      • Macrolides/azalides: Azithromycin injection, Azithromycin ophthalmic solution 1% (unavailable)
      • Nitrofurantoin oral suspension
      • Nitroimidazoles: Metronidazole injection
      • Penicillins: Ampicillin/sulbactam injection, Piperacillin/tazobactam injection
      • Tetracyclines: Doxycycline hyclate injection
      • Topical (miscellaneous) antibacterials: Bacitracin ophthalmic ointment, Mupirocin calcium 2% cream, Mupirocin calcium 2% nasal ointment (unavailable), Sulfanilamide 15% vaginal cream (unavailable)
      • Antifungal drugs: Clotrimazole 10 mg oral troches, Fluconazole injection, Griseofulvin oral tablets and suspension
      • Antiparasitic drugs: Pentamidine isethionate
      • Antiretroviral drugs: None
      • Antiviral drugs: Acyclovir injection, Cidofovir injection, Letermovir injection (unavailable)
      • Vaccines: Hepatitis B vaccine recombinant, Rabies vaccine (and immune globulin), 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: 
    • Recent discontinuations: Interferon alfa-2b (Intron A, in October 2019), Quinidine gluconate IV (in December 2017), 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).