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. To sign up for ID updates to your inbox, register here.
 

April 2021

2021 Sanford Guides Available for Preorder

• 2021 editions of The Sanford Guide to Antimicrobial Therapy are now available for preorder from the Sanford Guide Store. We expect to begin shipping in the next few weeks. This year's books include a 1-month trial of our digital editions.

SARS-CoV-2 / COVID-19

• Sanford Guide SARS-CoV-2 / COVID-19 material is freely available to all for the course of the pandemic.
• CDC: Interim public health recommendations for fully vaccinated people here.
• Currently authorized vaccines. See COVID-19 Prevention for table summarizing use and data.
• COVID-19 vaccination in cancer patients: preliminary recommendations from NCCN here.
• Guidelines on COVID-19 diagnosis, serology, treatment and management, and infection prevention: IDSA and NIH.
• A living WHO guideline on drugs for COVID-19 (BMJ 2020;370:m3379). Available here.
• A living WHO guideline on drugs to prevent COVID-19 (BMJ 2021;372:n526). Available here.
• Management of hospitalized adults with COVID-19: a European Respiratory Society living guideline (Eur Respir J 2021 Mar 10 [Epub ahead of print]). Available at PMC.

CDC Health Alert Network

• HAN #442 (Health Alert): The US CDC and FDA are reviewing data involving six US cases of cerebral venous sinus thrombosis in combination with thrombocytopenia in individuals who received the Johnson & Johnson (Janssen) COVID-19 vaccine. As of April 12, 2021, approximately 6.85 million doses of the J&J COVID-19 vaccine have been administered in the US. All six cases occurred among women aged 18–48 years. The interval from vaccine receipt to symptom onset ranged from 6–13 days. One patient died. Until the review is complete, CDC and FDA are recommending a pause in the use of the J&J COVID-19 vaccine out of an abundance of caution. Click here for the full Health Alert.

New Product Approval

• Oritavancin (Kimyrsa) for the treatment of adult patients with acute bacterial skin and skin structure infections caused by susceptible gram-positive microbes, including MRSA. This is the same indication as Orbactiv, the initial formulation of oritavancin to be FDA approved. The key difference of the new formulation is a one hour duration of infusion, rather than three hours. It also is supplied in different dose strengths and has different preparation instructions, including differences in reconstitution, dilution, and compatible diluents. Recommended dosage: 1200 mg IV over one hour as a single dose. A summer launch of the product is planned.

New or Updated Treatment Guidelines

• Clinical practice guidelines for the management of Clostridioides difficile infection, from the American Society of Colon and Rectal Surgeons (Dis Colon Rectum 2021 Mar 22 [Epub ahead of print]).
• 2020 guidelines for the use of antibiotics in pediatric patients with cancer or post-hematopoietic cell transplantation, from the 8th European Conference on Infections in Leukemia (Lancet Oncol 2021 Mar 31 [Epub ahead of print]).
• 2020 guidelines for the diagnosis, prevention, and treatment of invasive fungal diseases in pediatric patients with cancer or post-hematopoietic cell transplantation, from the 8th European Conference on Infections in Leukemia (Lancet Oncol 2021 Mar 31 [Epub ahead of print]).

Return of YF-VAX

• Sanofi Pasteur has announced that yellow fever vaccine YF-VAX is once again available for purchase in the United States. They expect to begin allowing orders through www.VaccineShoppe.com and www.VaxServe.com the week of April 5th. For more information, click here.

Commercial Availability of Artesunate for Injection

• Injectable Artesunate* for treatment of severe malaria is now commercially available in the US. There may be a delay before drug is stocked in pharmacies and hospitals. CDC will continue to distribute artesunate under its IND protocol in situations where the FDA-approved product is not yet available within 24 hours of a clinician requesting the drug. For more information, click here.

Drug Shortages (US)

• Antimicrobial drugs or vaccines in reduced supply or unavailable (as of April 11, 2021) due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons:
  • New on the list since March 8, 2021: None
  • Shortage recently resolved: Posaconazole injection
  • Antibacterial drugs in continued reduced supply:
    • Aminoglycosides: Amikacin injection, Gentamicin injection, Tobramycin injection, Tobramycin lyophilized powder for injection
    • Carbapenems: Meropenem injection
    • Cephalosporins: Cefazolin injection, Cefepime injection, Cefotaxime injection (FDA is allowing temporary importation of product from SteriMax in Canada, in conjunction with Apollo Pharmaceuticals and its distributor FFF Enterprises. Click here for details), Cefotetan injection, Cefoxitin injection, Ceftazidime injection, Ceftazidime/avibactam injection, Ceftolozane/tazobactam injection
    • Clindamycin injection
    • Fluoroquinolones: Ciprofloxacin 0.3% ophthalmic solution, Gemifloxacin tablets
    • Glycopeptides, glycolipopeptides, lipopeptides: Vancomycin injection
    • Macrolides/azalides: Azithromycin injection, Azithromycin ophthalmic solution 1% (unavailable)
    • Methanamine hippurate tablets
    • Nitrofurantoin oral suspension
    • Penicillins: Ampicillin/sulbactam injection, Piperacillin/tazobactam injection
    • Tetracyclines: None
    • Topical (miscellaneous) antibacterials: Neomycin and Polymyxin B sulfates GU irrigant, Neomycin and Polymyxin B sulfates and Dexamethasone ophthalmic ointment, Sulfacetamide 10%/Prednisolone 0.2% ophthalmic ointment (unavailable), Sulfanilamide 15% vaginal cream (unavailable)
  • Antimycobacterial drugs
    • Ethambutol tablets, Rifampin injection
  • Antifungal, antiparasitic, and antiviral drugs in continued reduced supply:
    • Antifungal drugs: Clotrimazole 10 mg oral troches
    • Antiparasitic drugs: Chloroquine tablets, Hydroxychloroquine tablets
    • Antiviral drugs: Acyclovir injection, Cidofovir injection
  • Vaccines in continued reduced supply:
    • Hepatitis B vaccine recombinant, Yellow Fever vaccine (YF-VAX is scheduled for re-launch in the US during  the week of April 5).

• Antimicrobial drugs newly discontinued: 
  • Recent discontinuations: Mupirocin calcium 2% cream (Bactroban [GSK], in June 2020), Bacitracin injection (in February 2020), Interferon alfa-2b (Intron A, in October 2019), Mupirocin calcium 2% nasal ointment (Bactroban Nasal [GSK], in August 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 more detailed information including estimated resupply dates, see https://www.ashp.org/Drug-Shortages/

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. To sign up for ID updates to your inbox, register here.
 

March 2021

SARS-CoV-2 / COVID-19

• Sanford Guide SARS-CoV-2 / COVID-19 material is freely available to all for the course of the pandemic.
• CDC: Interim public health recommendations for fully vaccinated people here.
• Janssen (J&J) vaccine: FDA EUA on 27 Feb 2021. Fact sheet for healthcare providers here.
• Currently authorized vaccines. See COVID-19 Prevention for table summarizing use and data.
• COVID-19 vaccination in cancer patients: preliminary recommendations from NCCN here.
• Guidelines on COVID-19 diagnosis, serology, treatment and management, and infection prevention: IDSA and NIH.
• A living WHO guideline on drugs for COVID-19 (BMJ 2020;370:m3379). Available here.
• Bamlanivimab + Etesevimab combination monoclonal antibody therapy for mild-moderate COVID-19. FDA EUA on 9 Feb 2021.
• NEW: a living WHO guideline on drugs to prevent COVID-19 (BMJ 2021;372:n526). Available here.

CDC Health Alert Network

• HAN #439 (Health Advisory): CDC is providing information on extensively drug-resistant (XDR) Salmonella Typhi (Typhi) infections among US residents without international travel, and treatment recommendations for XDR Typhi infection. Click here for the full health advisory.

2021 CDC Immunization Schedules

• Advisory Committee on Immunization Practices Recommended Immunization Schedule for Children and Adolescents Aged 18 Years or Younger — United States, 2021 (MMWR Morb Mortal Wkly Rep 2021;70:189). Immunization schedules are available here.
• Advisory Committee on Immunization Practices Recommended Immunization Schedule for Adults Aged 19 Years or Older — United States, 2021 (MMWR Morb Mortal Wkly Rep 2021;70:193). Immunization schedules are available here.

New or Updated Treatment Guidelines

• Summary of the recently published WHO/PAHO guidelines for diagnosing and managing disseminated histoplasmosis in people living with HIV (J Fungi [Basel] 2021;7:134); available at PMC. Full guidelines available here.
• Updated (2020) guidelines for the treatment of complicated skin and soft tissue infections, from the Surgical Infection Society (Surg Infect [Larchmt] 2021 Feb 26 [Epub ahead of print]). This is an update of the guidelines published in 2009.

Azole Dosing in Hepatic Impairment

• Two recent publications fill a few gaps in our knowledge of azole dosing in hepatic impairment. For isavuconazonium*, we know that no dosage adjustment is required in patients with mild to moderate impairment (Child-Pugh Class A and B), but no recommendations for severe impairment (Child-Pugh Class C) have been possible. However, recent pharmacokinetic data support a 50% dosage reduction in severe (Child-Pugh Class C) impairment (Antimicrob Agents Chemother 2021 Feb 22 [Epub ahead of print]).
• For voriconazole*, the manufacturer recommends that in patients with mild to moderate impairment, the standard loading dose is appropriate, but the maintenance dose should be halved. No recommendations for patients with severe impairment are provided. However, a pharmacokinetic study suggests that these recommendations may result in supratherapeutic concentrations. Study data indicate that a halved loading dose regimen be considered in cirrhotic patients, with a maintenance dose of 33% of the non-cirrhotic dose in patients with mild to moderate impairment, and 25% of the non-cirrhotic dose in patients with severe impairment (Pharmacotherapy 2021;41:172).

Quick Drug Interaction Reminder

• Ritonavir-boosted antiretroviral (ARV) regimens are associated with an increased risk of drug-drug interactions, with potentially serious outcomes. A patient stable on boosted fosamprenavir plus emtricitabine/tenofovir for ten years experienced significant hyperkalemia after beginning treatment with eplerenone, a mineralocorticoid receptor antagonist, for left ventricular dysfunction. ARVs and eplerenone were held, and the potassium normalized. Subsequent use of a dolutegravir-based regimen allowed for reinstitution of eplerenone with no recurrence of hyperkalemia. Eplerenone is a CYP3A4 substrate, fosamprenavir and ritonavir are potent inhibitors of CYP3A4, and dolutegravir does not inhibit CYP enzymes (Int J STD AIDS 2021 Feb 25 [Epub ahead of print]).

Drug Shortages (US)

• Antimicrobial drugs or vaccines in reduced supply or unavailable (as of March 8, 2021) due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons:
  • New on the list since February 9, 2021: Gentamicin injection, Rifampin injection
  • Shortage recently resolved: Amphotericin B injection, Fluconazole injection
  • Antibacterial drugs in continued reduced supply:
    • Aminoglycosides: Amikacin injection, Tobramycin injection, Tobramycin lyophilized powder for injection
    • Carbapenems: Meropenem injection
    • Cephalosporins: Cefazolin injection, Cefepime injection, Cefotaxime injection (FDA is allowing temporary importation of product from SteriMax in Canada, in conjunction with Apollo Pharmaceuticals and its distributor FFF Enterprises. Click here for details), Cefotetan injection, Cefoxitin injection, Ceftazidime injection, Ceftazidime/avibactam injection, Ceftolozane/tazobactam injection
    • Clindamycin injection
    • Fluoroquinolones: Ciprofloxacin 0.3% ophthalmic solution, Gemifloxacin tablets
    • Glycopeptides, glycolipopeptides, lipopeptides: Vancomycin injection
    • Macrolides/azalides: Azithromycin injection, Azithromycin ophthalmic solution 1% (unavailable)
    • Methanamine hippurate tablets
    • Nitrofurantoin oral suspension
    • Penicillins: Ampicillin/sulbactam injection, Piperacillin/tazobactam injection
    • Tetracyclines: None
    • Topical (miscellaneous) antibacterials: Neomycin and Polymyxin B sulfates GU irrigant, Neomycin and Polymyxin B sulfates and Dexamethasone ophthalmic ointment, Sulfacetamide 10%/Prednisolone 0.2% ophthalmic ointment (unavailable), Sulfanilamide 15% vaginal cream (unavailable)
  • Antimycobacterial drugs
    • Ethambutol tablets
  • Antifungal, antiparasitic, and antiviral drugs in continued reduced supply:
    • Antifungal drugs: Clotrimazole 10 mg oral troches, Posaconazole injection
    • Antiparasitic drugs: Chloroquine tablets, Hydroxychloroquine tablets
    • Antiviral drugs: Acyclovir injection, Cidofovir injection
  • Vaccines in continued reduced supply:
    • Hepatitis B vaccine recombinant, 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: Mupirocin calcium 2% cream (Bactroban [GSK], in June 2020), Bacitracin injection (in February 2020), Interferon alfa-2b (Intron A, in October 2019), Mupirocin calcium 2% nasal ointment (Bactroban Nasal [GSK], in August 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 more detailed information including estimated resupply dates, see https://www.ashp.org/Drug-Shortages/

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. To sign up for ID updates to your inbox, register here.
 
Sanford Guide ID Update features current developments in infectious diseases, curated by the Sanford Guide Editorial Board. If you received this message from a colleague, subscribe now.
 

February 2021

SARS-CoV-2 / COVID-19

• Sanford Guide SARS-CoV-2 / COVID-19 material is freely available to all for the course of the pandemic.
• COVID-19 Vaccine (Emergency Use Authorization). See COVID-19 Prevention for summary of FDA Provider Fact Sheet / Emergency Prescribing Information for each.
  • Pfizer-BioNTech COVID-19 Vaccine on 11 Dec 2020 (US FDA).
  • Moderna COVID-19 Vaccine on 18 Dec 2020 (US FDA).
  • Oxford AstraZeneca COVID-19 Vaccine on 30 Dec 2020 (UK)
• Vaccine development pipeline: see COVID-19, Prevention for summary of other vaccine development and clinical trials.
• Guidelines on COVID-19 diagnosis, serology, treatment and management, and infection prevention: IDSA and NIH.
• A living WHO guideline on drugs for COVID-19 (BMJ 2020;370:m3379). Available on the BMJ website.
• Surviving Sepsis Campaign guidelines on the management of adults with COVID-19 in the ICU: first update (Crit Care Med 2021 Jan 28 [Epub ahead of print]). Available on the journal website.

New Product Approvals

• Cabotegravir injectable and rilpivirine injectable (Cabenuva), a two-drug co-packaged product, indicated to replace the current antiretroviral regimen in adult patients with HIV-1 infection who are virologically suppressed (RNA <50 copies/mL) on a stable regimen with no history of treatment failure and no known or suspected resistance to either component. Lead-in dosing with oral cabotegravir and oral rilpivirine should be used for one month before initiation of injectable dosing to assess tolerance. Recommended dosing schedule: Cabotegravir/rilpivirine 600 mg/900 mg IM on the last day of oral lead-in, then 400 mg/600 mg IM every month thereafter.
• Cabotegravir tablets (Vocabria) for use (in combination with oral rilpivirine) as oral lead-in therapy to assess tolerability prior to administration of the injectable forms, and as oral therapy for patients who will miss planned injection dosing. Lead-in dosing is cabotegravir 30 mg (+ rilpivirine 25 mg) once daily for one month. If a patient plans to miss a scheduled injection by more than seven days, daily oral therapy with cabotegravir 30 mg plus rilpivirine 25 mg is taken to replace up to two consecutive monthly injections. The first dose of oral therapy should be taken approximately one month after the last injections and continued until the day injection dosing is resumed. Product availability: 30 mg tablets.

New or Updated Treatment Guidelines

• Updated evidence-based treatment guidelines for MRSA from the UK (JAC-Antimicrobial Resistance 2021;3:dlaa114). The guidelines were last updated in 2008 and are available on the journal website.
• Evidence-based guidelines for the treatment of Helicobacter pylori infection in Korea in 2020 (Gut Liver 2021 Jan 20 [Epub ahead of print]). Available on the journal website.
• Chinese clinical practice guidelines for the prevention of mother-to-child transmission of hepatitis B virus, launched by the Society of infectious Diseases, Chinese Medical Association (J Clin Transl Hepatol 2020;8:397). Available at PMC.
• Prophylaxis, diagnosis and therapy of infections in patients undergoing high-dose chemotherapy and autologous haematopoietic stem cell transplantation. 2020 update of the recommendations of the Infectious Diseases Working Party of the German Society of Hematology and Medical Oncology (Ann Hematol 2021;100:321). Available at PMC.
• Clinical practice guidelines for adult appendicitis, from the French Society of Digestive Surgery and the Society of Abdominal and Digestive Imaging (J Visc Surg 2021 Jan 5 [Epub ahead of print]).
• Executive summary of the JSMM clinical practice guidelines for the diagnosis and treatment of Cryptococcosis 2019, from the Japanese Society for Medical Mycology (Med Mycol J 2020;61:61). The executive summary is available here.

A Few Drug Pearls

• Based on a pharmacokinetic study in six critically ill hematology patients, no a priori dose adjustment of posaconazole during ECMO is recommended. Some trough concentrations were below the lower limit for treatment, however, so therapeutic drug monitoring is recommended to ensure adequate drug exposure (J Antimicrob Chemother 2021 Jan 29 [Epub ahead of print]).
• A recent report describes the inappropriate use of IM benzylpenicillin G rather than benzathine penicillin G in one patient with syphilis (resulting in treatment failure), and the attempted use of IM benzylpenicillin G in another. Other disturbing treatment errors with long-acting penicillin G products have occurred, such as the improper use of the procaine-benzathine preparation of penicillin G (instead of benzathine) in 429 syphilis patients over a five-year period (MMWR 2005;54:217). Recent product shortages have likely increased the risk of error (Sex Transm Infect 2020;96:552).
• The effects of ECMO on vancomycin pharmacokinetic parameters are conflicting and poorly understood. Changes may be minimal, and no standard dosage adjustment seems reasonable. However, aggressive therapeutic drug monitoring is recommended to achieve efficacy and safety targets. Continuous infusion may lessen PK changes. References: Antimicrob Agents Chemother 2021;65:e02408-20; J Clin Pharm Ther 2020;45:1066; Clin Pharmacokinet 2020;59:1575.

Drug Shortages (US)

• Antimicrobial drugs or vaccines in reduced supply or unavailable (as of February 9, 2021) due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons:
  • New on the list since January 13, 2021: Posaconazole injection
  • Shortage recently resolved: Fluconazole injection, Tobramycin lyophilized powder for injection
  • Antibacterial drugs in continued reduced supply:
    • Aminoglycosides: Amikacin injection, Tobramycin injection
    • Carbapenems: Meropenem injection
    • Cephalosporins: Cefazolin injection, Cefepime injection, Cefotaxime injection (FDA is allowing temporary importation of product from SteriMax in Canada, in conjunction with Apollo Pharmaceuticals and its distributor FFF Enterprises. Click here for details), Cefotetan injection, Cefoxitin injection, Ceftazidime injection, Ceftazidime/avibactam injection, Ceftolozane/tazobactam injection
    • Clindamycin injection
    • Fluoroquinolones: Ciprofloxacin 0.3% ophthalmic solution, Gemifloxacin tablets
    • Glycopeptides, glycolipopeptides, lipopeptides: Vancomycin injection
    • Macrolides/azalides: Azithromycin injection, Azithromycin ophthalmic solution 1% (unavailable)
    • Methanamine hippurate tablets
    • Nitrofurantoin oral suspension
    • Penicillins: Ampicillin/sulbactam injection, Piperacillin/tazobactam injection
    • Tetracyclines: None
    • Topical (miscellaneous) antibacterials: Neomycin and Polymyxin B sulfates GU irrigant, Neomycin and Polymyxin B sulfates and Dexamethasone ophthalmic ointment, Sulfacetamide 10%/Prednisolone 0.2% ophthalmic ointment (unavailable), Sulfanilamide 15% vaginal cream (unavailable)
  • Antimycobacterial drugs
    • Ethambutol tablets
  • Antifungal, antiparasitic, and antiviral drugs in continued reduced supply:
    • Antifungal drugs: Amphotericin B injection, Clotrimazole 10 mg oral troches
    • Antiparasitic drugs: Chloroquine tablets, Hydroxychloroquine tablets
    • Antiviral drugs: Acyclovir injection, Cidofovir injection
  • Vaccines in continued reduced supply:
    • Hepatitis B vaccine recombinant, 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: Mupirocin calcium 2% cream (Bactroban [GSK], in June 2020), Bacitracin injection (in February 2020), Interferon alfa-2b (Intron A, in October 2019), Mupirocin calcium 2% nasal ointment (Bactroban Nasal [GSK], in August 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 more detailed information including estimated resupply dates, see https://www.ashp.org/Drug-Shortages/

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. To sign up for ID updates to your inbox, register here.
 
Sanford Guide ID Update features current developments in infectious diseases, curated by the Sanford Guide Editorial Board. If you received this message from a colleague, subscribe now.
 

January 2021

SARS-CoV-2 / COVID-19

• Sanford Guide SARS-CoV-2 / COVID-19 material is freely available to all for the course of the pandemic.
• COVID-19 Vaccine (Emergency Use Authorization). See COVID-19 Prevention for summary of FDA Provider Fact Sheet / Emergency Prescribing Information for each.
  • Pfizer-BioNTech COVID-19 Vaccine on 11 Dec 2020 (US FDA).
  • Moderna COVID-19 Vaccine on 18 Dec 2020 (US FDA).
  • Oxford AstraZeneca COVID-19 Vaccine on 30 Dec 2020 (UK)
• Vaccine development pipeline: see COVID-19, Prevention for summary of other vaccine development and clinical trials.
• Guidelines on COVID-19 diagnosis, serology, treatment and management, and infection prevention: IDSA and NIH.
• A living WHO guideline on drugs for COVID-19 (BMJ 2020;370:m3379). Available on the BMJ website.

Voluntary Product Recall

• Merck has initiated a global product recall of ceftolozane-tazobactam 1.5 gm vials. Due to a recent issue identified during routine testing (sterility test results of seven batches were out of specification), product manufacturing has been temporarily stopped. Five of these batches tested positive for Ralstonia pickettii and two batches produced turbid results that could not be further identified. The seven batches were not released to the market. While all product distributed to the market has met the registered specifications for release, it was manufactured on the same equipment as the affected batches. As a result, the company has initiated a voluntary Class II (health care provider level) global recall of all ceftolozane-tazobactam within expiry.

New Product Approval

• Ansuvimab-zykl (Ebanga), a human monoclonal antibody, for the treatment for Zaire ebolavirus (Ebolavirus) infection in adults and children. The recommended dosage is a single 50 mg/kg IV infusion. It is available in lyophilized form.

Update to CDC Treatment Guidelines for Gonococcal Infection

• For treatment of uncomplicated urogenital, rectal, or pharyngeal gonorrhea, CDC now recommends a single 500 mg IM dose of ceftriaxone. For persons weighing ≥150 kg (300 lbs), a single 1 gm IM dose of ceftriaxone should be administered. If chlamydial infection has not been excluded, doxycycline 100 mg orally twice a day for 7 days (not azithromycin) is recommended (MMWR Morb Mortal Wkly Rep 2020;69:1911). The full update, which includes other changes such as ceftriaxone dosing for pharyngeal gonorrhea and cefixime dosing (alternative regimen), is available at PMC.

Other New or Updated Treatment Guidelines

• Updated recommendations for the use of antiretroviral drugs in pregnant women with HIV infection and interventions to reduce perinatal HIV transmission in the US, from the HHS Panel on Treatment of Pregnant Women with HIV Infection and Prevention of Perinatal Transmission. The recommendations are available here.
• Guidelines for diagnosis and management of intraabdominal infection, from the Chinese Society of Surgical Infection and Intensive Care and the Chinese College of Gastrointestinal Fistula Surgeons (Clin Infect Dis 2020;71(suppl 4):S337).
• Updated guidelines for therapeutic drug monitoring of vancomycin, from the Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society (Clin Infect Dis 2020;71(suppl 4):S363). The guidelines were last updated in 2015.
• Southern African guidelines on the safe, easy, and effective use of pre-exposure prophylaxis to prevent HIV acquisition (South Afr J HIV Med 2020;21:1152). The guidelines were last updated in 2016 and are available at PMC.

Drug Shortages (US)

• Antimicrobial drugs or vaccines in reduced supply or unavailable (as of January 3, 2021) due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons:
  • New on the list since December 27, 2020: Posaconazole injection
  • Shortage recently resolved: Doxycycline injection, Metronidazole injection, Pentamidine isethionate
  • Antibacterial drugs in continued reduced supply:
    • Aminoglycosides: Amikacin injection, Tobramycin injection, Tobramycin lyophilized powder for injection
    • Carbapenems: Meropenem injection
    • Cephalosporins: Cefazolin injection, Cefepime injection, Cefotaxime injection (FDA is allowing temporary importation of product from SteriMax in Canada, in conjunction with Apollo Pharmaceuticals and its distributor FFF Enterprises. Click here for details), Cefotetan injection, Cefoxitin injection, Ceftazidime injection, Ceftazidime/avibactam injection, Ceftolozane/tazobactam injection
    • Clindamycin injection
    • Fluoroquinolones: Ciprofloxacin 0.3% ophthalmic solution, Gemifloxacin tablets
    • Glycopeptides, glycolipopeptides, lipopeptides: Vancomycin injection
    • Macrolides/azalides: Azithromycin injection, Azithromycin ophthalmic solution 1% (unavailable)
    • Methanamine hippurate tablets
    • Nitrofurantoin oral suspension
    • Penicillins: Ampicillin/sulbactam injection, Piperacillin/tazobactam injection
    • Tetracyclines: None
    • Topical (miscellaneous) antibacterials: Neomycin and Polymyxin B sulfates GU irrigant, Neomycin and Polymyxin B sulfates and Dexamethasone ophthalmic ointment, Sulfacetamide 10%/Prednisolone 0.2% ophthalmic ointment (unavailable), Sulfanilamide 15% vaginal cream (unavailable)
  • Antimycobacterial drugs
    • Ethambutol tablets
  • Antifungal, antiparasitic, and antiviral drugs in continued reduced supply:
    • Antifungal drugs: Amphotericin B injection, Clotrimazole 10 mg oral troches, Fluconazole injection
    • Antiparasitic drugs: Chloroquine tablets, Hydroxychloroquine tablets
    • Antiviral drugs: Acyclovir injection, Cidofovir injection
  • Vaccines in continued reduced supply:
    • Hepatitis B vaccine recombinant, 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: Mupirocin calcium 2% cream (Bactroban [GSK], in June 2020), Bacitracin injection (in February 2020), Interferon alfa-2b (Intron A, in October 2019), Mupirocin calcium 2% nasal ointment (Bactroban Nasal [GSK], in August 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 more detailed information including estimated resupply dates, see https://www.ashp.org/Drug-Shortages/

During our 30 minute webinar on vancomycin monitoring, we received a number of questions from attendees. We answered most of these during the session, but still had a few left to cover. Sanford Guide editor Douglas Black PharmD prepared answers to these questions.

Q. Does the 400-600 µg x hr/mL target apply to all serious MRSA infections, or is a different target recommended for endocarditis, osteomyelitis, meningitis, etc.?

A. At present, the data allow us only to identify 400-600 µg x hr/mL as the appropriate AUC24 target for serious MRSA infection. There is no compelling evidence to support a different target for a specific MRSA infection. We are in need of more data supporting AUC monitoring for meningitis (since S. pneumoniae is the likely pathogen in adults, not S. aureus).

Q. What about the use of AUC monitoring for other infections?

A. The revised guidelines are based on improved efficacy and safety data for AUC24/MIC monitoring for serious MRSA infections. The guidelines exclude nonserious infections such as urinary tract infections and skin and soft tissue infections. In addition, they do not apply to other pathogens such as methicillin-susceptible S. aureus, coagulase-negative Staphylococcus, or streptococci (we need data on the appropriate AUC24 target for these). The guidelines also do not apply to MRSA infections for which the vancomycin MIC is known to be greater than 1 µg/mL by broth microdilution.

Q. When doing AUC monitoring, why is it recommended to assume a vancomycin MIC of 1 µg/mL?

A. Vancomycin MIC depends on the method used to measure it. For example, the vancomycin MIC determined by E-test methodology tends to be 1.5-2x higher than the MIC measured by broth microdilution (BMD). There is known disagreement between commercially available MIC automated testing methods, E-test, and BMD, complicated by ±1 doubling dilution variability in results. We also know that at most institutions, the vancomycin MIC by BMD is 1 µg/mL or less (and there hasn’t been much MIC creep). Therefore, for monitoring purposes the vancomycin MIC for MRSA should be assumed to be 1 µg/mL (unless it is known to be something different using BMD).

Q. Can we use AUC monitoring during AKI?

A. We believe the AUC target monitoring range (400-600 µg x hr/mL) also applies to patients with renal dysfunction, although outcome studies validating this target for patients receiving hemodialysis, a hybrid hemodialysis therapy such as SLED, or CRRT are not available. Patients with unstable renal function are certainly going to be a challenge. We need more published data to help us with AUC monitoring in renal dysfunction; for now, trough-based dosing or dosing by concentration in some patients might be more practical. For example, the guideline recommendation for patients on hemodialysis is to monitor by targeting a predialysis concentration of 15-20 µg/mL, which will serve as a reasonable proxy for an AUC of 400-600 µg x hr/mL.