2020 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 2020 Infectious Disease Update

New or Updated Treatment Guidelines

  • Updated HHS panel Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV. The guidelines are available on the AIDSinfo website.
  • Updated HHS Recommendations for the Use of Antiretroviral Drugs in Pregnant Women with HIV Infection and Interventions to Reduce Perinatal HIV Transmission in the US. The guidelines are available on the AIDSinfo website.
  • Prevention and Treatment of Cancer-Related Infections, version 1.2020, from the National Comprehensive Cancer Network (NCCN). The guidelines are available on the NCCN website.

From CDC

  • Revised recommendations for the use of anthrax vaccine in the United States, from the CDC Advisory Committee on Immunization Practices (MMWR Recomm Rep 2019;68(RR-4):1-14). These recommendations update the 2009 release and are available on the CDC website.

Drug Shortages (US)

  • Antimicrobial drugs or vaccines in reduced supply or unavailable (as of January 5, 2020) due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons:
    • [New on the list since December 9]: Neomycin and Polymyxin B sulfates GU irrigant
    • [Shortage recently resolved]: Letermovir injection, Rabies immune globulin, Rabies vaccine
    • [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), Erythromycin lactobionate injection
      • 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), Sulfacetamide 10%/Prednisolone 0.2% ophthalmic ointment, 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
      • 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: 
    • 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 2020 Infectious Disease Update

SARS-CoV-2

  • WHO officially names the virus 2019-nCoV as SARS-CoV-2*. The disease caused by the virus is named COVID-19.
  • Rapid advice guideline for the diagnosis and treatment of 2019-nCoV pneumonia, prepared in accordance with the methodology and general rules of WHO Guideline Development and the WHO Rapid Advice Guidelines (Mil Med Res 2020;7:4). The guidelines are available on the journal website.

New or Updated Treatment Guidelines

  • Clinical practice guidelines for the prevention and management of viral hepatitis in inflammatory bowel disease, from the Korean Association for the Study of Intestinal Diseases (Intest Res 2020;18:18). The guidelines are available on the journal website.
  • S2k guidelines for the diagnosis and treatment of herpes zoster and postherpetic neuralgia (J Dtsch Dermatol Ges 2020;18:55). These guidelines were developed on behalf of the German Herpes Management Forum under the auspices of the Paul Ehrlich Society of Chemotherapy.
  • Surviving Sepsis Campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children, from the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies (Pediatr Crit Care Med 2020;21:e52). The guidelines are available on the journal website.
  • Clinical practice guidelines for the management of vascular graft and stent graft infections, from the European Society for Vascular Surgery (Eur J Vasc Endovasc Surg 2020 Jan 30 [Epub ahead of print]).

From CDC

  • At its October 2019 meeting, the Advisory Committee on Immunization Practices (ACIP) voted to approve the 2020 Recommended Child and Adolescent Immunization Schedule for Ages 18 Years or Younger, and the 2020 Recommended U.S. Adult Immunization Schedule for Persons Aged 19 Years and Older. Tables and accompanying notes can be found on the CDC website.
  • Guidelines for the treatment of latent tuberculosis infection, from the National Tuberculosis Controllers Association and CDC (MMWR Recomm Rep 2020;69(No. RR-1):1–11). The guidelines are available on the CDC website.

From FDA

  • The US FDA has requested that all current manufacturers of bacitracin for injection voluntarily withdraw their product from the market. Based on FDA’s review of currently available data, FDA believes that the potential problems associated with bacitracin for injection are sufficiently serious to remove the drug from the market. This requested voluntary withdrawal does not impact approved topical or ophthalmic drugs that contain bacitracin. More information can be found here.

Drug Shortages (US)

  • Antimicrobial drugs or vaccines in reduced supply or unavailable (as of February 8, 2020) due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons:
    • [New on the list since January 5]: Erythromycin 0.5% ophthalmic ointment
    • [Shortage recently resolved]: Doxycycline hyclate injection, Letermovir injection, Rabies immune globulin, Rabies vaccine
    • [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 (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), 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), Erythromycin lactobionate injection
      • Nitrofurantoin oral suspension
      • Nitroimidazoles: Metronidazole injection
      • Penicillins: Ampicillin/sulbactam injection, Piperacillin/tazobactam injection
      • Tetracyclines: None
      • Topical (miscellaneous) antibacterials: Bacitracin ophthalmic ointment (unavailable), Mupirocin calcium 2% cream, Mupirocin calcium 2% nasal ointment (unavailable), Neomycin and Polymyxin B sulfates GU irrigant, Sulfacetamide 10%/Prednisolone 0.2% ophthalmic ointment, 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
      • 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: 
    • 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).

March 2020 Infectious Disease Update Pt. 1

Given the current SARS-CoV-2 situation, Sanford Guide is releasing this special ID Update with the latest information. A more comprehensive ID Update will be released later this month.

SARS-CoV-2*


March 2020 Infectious Disease Update Pt. 2

SARS-CoV-2 / COVID-19

  • Sanford Guide SARS-CoV-2 / COVID-19 material is freely available to all for the course of the pandemic. Click the link above.
  • We advocate STAY AT HOME except for essential activities, e.g., food, medicines, healthcare and essential work such as police, fire, sanitation and healthcare.
  • AVOID CROWDS  AND/OR CONGESTED AREAS. AVOID COMPLACENCY!

2020 Sanford Guides

  • We anticipate that 2020 print editions of The Sanford Guide to Antimicrobial Therapy will become available in the coming weeks. To receive a notice as soon as the books are released, sign up here.

New or Updated Treatment Guidelines

Drug Shortages (US)

  • Antimicrobial drugs or vaccines in reduced supply or unavailable (as of March 20, 2020) due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons:
    • [New on the list since February 8]: Benzylpenicilloyl polylysine (Pre-Pen), Ceftazidime/avibactam, Chloroquine tablets, Gemifloxacin tablets, Gentamicin injection, Hydroxychloroquine tablets, Methenamine hippurate tablets, Neomycin and Polymyxin B sulfates and Dexamethasone ophthalmic ointment
    • [Shortage recently resolved]: Erythromycin 0.5% ophthalmic ointment, Metronidazole injection, Tuberculin (PPD)
    • [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 (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), 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), Erythromycin lactobionate injection
      • Nitrofurantoin oral suspension
      • Nitroimidazoles: None
      • Penicillins: Ampicillin/sulbactam injection, Piperacillin/tazobactam injection
      • Tetracyclines: None
      • Topical (miscellaneous) antibacterials: Bacitracin ophthalmic ointment, Mupirocin calcium 2% cream, Mupirocin calcium 2% nasal ointment (unavailable), Neomycin and Polymyxin B sulfates GU irrigant, Sulfacetamide 10%/Prednisolone 0.2% ophthalmic 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
      • 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: 
    • Recent discontinuations: Bacitracin inection (in February 2020), 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).

April 2020 Infectious Disease Update

2020 Sanford Guide Print Editions Now Available

SARS-CoV-2 / COVID-19

Other New or Updated Treatment Guidelines

Drug Shortages (US)

  • Antimicrobial drugs or vaccines in reduced supply or unavailable (as of April 8, 2020) due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons:
    • [New on the list since March 20]: Doxycycline injection, Tobramycin lyophilized powder for injection
    • [Shortage recently resolved]: Acyclovir injection, Dalfopristin-Quinupristin injection, Daptomycin injection, Erythromycin lactobionate injection
    • [Continue to be in reduced supply]
      • Aminoglycosides: Amikacin injection, Gentamicin injection, Gentamicin ophthalmic ointment (unavailable), Tobramycin injection
      • Benzylpenicilloyl polylysine (Pre-Pen)
      • 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), Cefoxitin injection, Ceftazidime injection, Ceftazidime/avibactam injection, Cefuroxime 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
      • Nitroimidazoles: None
      • Penicillins: Ampicillin/sulbactam injection, Piperacillin/tazobactam injection
      • Tetracyclines: None
      • Topical (miscellaneous) antibacterials: Bacitracin ophthalmic ointment, Mupirocin calcium 2% cream, Mupirocin calcium 2% nasal ointment (unavailable), 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)
      • Antifungal drugs: Clotrimazole 10 mg oral troches, Fluconazole injection, Griseofulvin oral tablets and suspension
      • Antiparasitic drugs: Chloroquine tablets, Hydroxychloroquine tablets, Pentamidine isethionate
      • Antiretroviral drugs: None
      • Antiviral drugs: Cidofovir injection
      • 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: 
    • Recent discontinuations: Bacitracin inection (in February 2020), 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).

May 2020 Infectious Disease Update

Free Trials for Hospitals and Health Systems

  • Sanford Guide is currently offering free 60-day trials of Sanford Guide All Access (web & mobile) to hospitals and health systems. Click here for more information.

SARS-CoV-2 / COVID-19

Updated Pediatric HIV Guidelines

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

Other New or Updated Treatment Guidelines

  • British Thoracic Society guideline for the use of long-term macrolides in adults with respiratory disease (Thorax 2020;75:370). The guidelines are available on the BTS website.
  • Diagnosis and treatment of acute appendicitis: 2020 update of the World Society of Emergency Surgery (WSES) Jerusalem guidelines (World J Emerg Surg 2020;15:27). The guidelines are available on the WJES website.
  • 2020 update of the World Society of Emergency Surgery (WSES) guidelines for the management of acute colonic diverticulitis in the emergency setting (World J Emerg Surg 2020;15:32). The guidelines are available on the WJES website.
  • Clinical practice guidelines for the treatment of left-sided colonic diverticulitis, from the American Society of Colon and Rectal Surgeons (Dis Colon Rectum 2020;63:728). The guidelines are available on the journal website.
  • Position paper on antimicrobial therapeutic drug monitoring in critically ill patients from these endorsing organizations: European Society of Intensive Care Medicine (ESICM), Pharmacokinetic/Pharmacodynamic and Critically Ill Patient Study Groups of European Society of Clinical Microbiology and Infectious Diseases (ESCMID), International Association for Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT), and International Society of Antimicrobial Chemotherapy (ISAC) (Intensive Care Med 2020 May 7 [Epub ahead of print]).

Dosing Pearls

  • IV infusion over 30 minutes is the recommended method of ceftriaxone* administration in adults. IV push administration over 1-2 minutes allows for a decrease in time to administration, which might positively affect outcome in a time-sensitive situation such as sepsis. In a retrospective study of 753 administrations in an emergency department, the total adverse event rate with IV push ceftriaxone was 0.13%, similar to or lower than previously reported. A cost savings for the hospital was also realized (Am J Emerg Med 2020 Mar 30 [Epub ahead of print]).
  • The effect of extracorporeal membrane oxygenation (ECMO) on TMP-SMX* pharmacokinetics has not been described. A 33-yo male with recently diagnosed HIV infection and Pneumocystis jirovecii pneumonia requiring venovenous ECMO for refractory respiratory failure was treated with high-dose TMP-SMX. No significant effect on trimethoprim or sulfamethoxazole pharmacokinetics was found, suggesting that no dose adjustment in ECMO may be necessary (Pharmacotherapy 2020 May 7 [Epub ahead of print]).
  • For CMV prophylaxis in solid-organ transplant (SOT) patients, valganciclovir* (a ganciclovir prodrug) is typically given in a dose of 900 mg po q24h. A ganciclovir trough concentration of ≥0.6 µg/mL in this setting is a reasonable target. Until recently, specific valganciclovir dose adjustment data in CRRT have been scant. In a prospective PK study in ten SOT patients receiving CVVHD, eight (80%) achieved the target ganciclovir concentration at steady state using valganciclovir 450 po q24h. The mean ganciclovir concentration was 2.27 µg/mL. Most patients had minimal enteral nutrition during the study period. Neutropenia was not observed; thrombocytopenia was common but likely multifactorial (Clin Infect Dis 2020 May 7 [Epub ahead of print]).

Drug Shortages (US)

  • Antimicrobial drugs or vaccines in reduced supply or unavailable (as of May 10, 2020) due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons:
    • New on the list since April 8Erythromycin 0.5% ophthalmic ointment
    • Shortage recently resolvedBenzylpenicilloyl polylysine (Pre-Pen), Ceftazidime/avibactam injection
    • Antibacterial drugs in continued reduced supply:
      • Aminoglycosides: Amikacin injection, Gentamicin injection, Gentamicin ophthalmic ointment (unavailable), 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), Cefoxitin injection, Ceftazidime injection, Cefuroxime 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
      • Nitroimidazoles: None
      • Penicillins: Ampicillin/sulbactam injection, Piperacillin/tazobactam injection
      • Tetracyclines: Doxycycline injection
      • Topical (miscellaneous) antibacterials: Bacitracin ophthalmic ointment, Mupirocin calcium 2% cream, Mupirocin calcium 2% nasal ointment (unavailable), 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)
    • Antifungal, antiparasitic, and antiviral drugs in continued reduced supply:
      • Antifungal drugs: Clotrimazole 10 mg oral troches, Fluconazole injection, Griseofulvin oral tablets and suspension
      • Antiparasitic drugs: Chloroquine tablets, Hydroxychloroquine tablets, Pentamidine isethionate
      • Antiviral drugs: Cidofovir injection
    • Vaccines in coninued reduced supply:
      • 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: 
    • Recent discontinuations: Bacitracin inection (in February 2020), 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).

June 2020 Infectious Disease Update

SARS-CoV-2 / COVID-19

  • Sanford Guide SARS-CoV-2 / COVID-19 material is freely available to all for the course of the pandemic.
  • Remdesivir remains the treatment option for severe, hospitalized COVID-19.
  • Guidelines on COVID-19 diagnosis, treatment and management, and infection prevention: IDSA and NIH

IV Artesunate FDA approved

  • Artesunate* for Injection has been approved by the US FDA for the initial treatment of severe malaria in adult and pediatric patients. The recommended dosage is 2.4 mg/kg IV at 0, 12, and 24 hours, and thereafter once daily until the patient is able to tolerate oral therapy. Commercial availability is expected in late 2020.

New or Updated Treatment Guidelines

Practice Pearls

  • Non-renal clearance accounts for about 65% of the total clearance of linezolid. Despite this fact, no dosage adjustment for linezolid in hepatic dysfunction is currently recommended. However, a PK modeling study shows that overexposure may result in patients with liver cirrhosis, suggesting the need for a dosage reduction depending on pathogen MIC (Antimicrob Agents Chemother 2020;64: e00133-20).
  • Trimethoprim inhibits the renal tubular secretion of creatinine, causing a fall in creatinine excretion and an increase in the serum creatinine concentration WITHOUT a change in glomerular filtrate rate (GFR). The mechanism is believed to be the inhibition (by TMP) of drug transporters in the proximal tubule (OCT2, OCT3, MATE1, and MATE2-K) also used by creatinine. The expected magnitude of increase is around 30% (Drug Metab Pharmacokinet 2018;33:103).
  • Published data regarding the effect of ECMO on ceftolozane-tazobactam pharmacokinetics are scant. An investigation using both an ex vivo and an in vivo (porcine) model found minimal circuit sequestration and a modest decrease in ceftolozane and tazobactam clearance. The data suggest that no change in ceftolozane-tazobactam dosing in patients undergoing ECMO is warranted, but this recommendation requires confirmation (J Transl Med 2020;18:213).

Drug Shortages (US)

  • Antimicrobial drugs or vaccines in reduced supply or unavailable (as of June 10, 2020) due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons:
    • New on the list since May 10Acyclovir injection, Ethambutol tablets, Metronidazole injection
    • Shortage recently resolvedGentamicin ophthalmic ointment
    • 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), Cefoxitin injection, Ceftazidime injection, Cefuroxime 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), Erythromycin 0.5% ophthalmic ointment
      • Methanamine hippurate tablets
      • Nitrofurantoin oral suspension
      • Nitroimidazoles: None
      • Penicillins: Ampicillin/sulbactam injection, Piperacillin/tazobactam injection
      • Tetracyclines: Doxycycline injection
      • Topical (miscellaneous) antibacterials: Bacitracin ophthalmic ointment, Mupirocin calcium 2% cream, Mupirocin calcium 2% nasal ointment (unavailable), 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)
    • Antifungal, antiparasitic, and antiviral drugs in continued reduced supply:
      • Antifungal drugs: Clotrimazole 10 mg oral troches, Fluconazole injection, Griseofulvin oral tablets and suspension
      • Antiparasitic drugs: Chloroquine tablets, Hydroxychloroquine tablets, Pentamidine isethionate
      • Antiviral drugs: Cidofovir injection
    • Vaccines in coninued reduced supply:
      • 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: 
    • Recent discontinuations: Bacitracin inection (in February 2020), 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).

July 2020 Infectious Disease Update

SARS-CoV-2 / COVID-19

  • Sanford Guide SARS-CoV-2 / COVID-19 material is freely available to all for the course of the pandemic.
  • Guidelines on COVID-19 diagnosis, treatment and management, and infection prevention: IDSA and NIH.

New Drug Approval

  • Fostemsavir (Rukobia), an HIV-1 attachment inhibitor, indicated (in combination with other antiretrovirals) for heavily treatment-experienced adults with multidrug-resistant HIV-1 infection failing their current ARV regimen due to resistance, intolerance, or safety considerations. Recommended dosage: one 600 mg extended-release tablet twice daily, with or without food.

Possible Remdesivir Drug Interaction

  • A critically ill COVID-19 patient developed liver toxicity five days after initiation of remdesivir therapy. Two days after beginning remdesivir he was also administered amiodarone for new onset atrial fibrillation, and he had recently received a five-day course of chloroquine (last dose nine days before beginning remdesivir). Remdesivir is a P-glycoprotein (PGP) substrate, and amiodarone and chloroquine inhibit PGP. PGP is an efflux transporter present in the intestine, liver, and kidney; in the liver it transports drug molecules from the hepatocyte into the bile for excretion. It is thus possible that this case of presumed remdesivir hepatotoxicity was fostered by a drug-drug interaction that raised hepatocellular concentrations of remdesivir above the toxicity threshold (Clin Infect Dis 2020 Jun 28 [Epub ahead of print]).

Dolutegravir Dispersible Tablets for Pediatric Patients

  • Dolutegravir* 5 mg tablets for oral solution (Tivicay PD) have been approved for the treatment of HIV-1 infection in pediatric patients (treatment-naive or -experienced but INSTI-naive) aged at least 4 weeks and weighing at least 3 kg. These tablets are not bioequivalent to the previously approved dolutegravir tablets and not interchangeable on a mg-per-mg basis.

New or Updated Treatment Guidelines

  • Guidelines on diagnostic procedures for suspected beta-lactam antibiotic hypersensitivity from the German and Austrian professional associations for allergology, and the Paul-Ehrlich Society for Chemotherapy (Allergol Select 2020;4:11). The guidelines are available at PMC.
  • Clinical practice guidelines for the diagnosis and management of acute otitis media in children (2018 update), from committee members of the Japan Otological Society, Japan Society for Infection and Aerosol in Otorhinolaryngology, and the Japan Society for Pediatric Otorhinolaryngology (Auris Nasus Larynx 2020 June 20;S0385-8146). The guidelines are available on the journal website.
  • Executive summary of clinical practice guidelines for the treatment of nontuberculous mycobacterial pulmonary disease, from the ATS, ERS, ESCMID, and IDSA (Clin Infect Dis 2020;Jul 6 [Epub ahead of print]). The summary is available on the journal website.

Drug Shortages (US)

  • Antimicrobial drugs or vaccines in reduced supply or unavailable (as of July 7, 2020) due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons:
    • New on the list since June 10Ceftazidime/avibactam injection
    • Shortage recently resolvedCefuroxime injection, Erythromycin 0.5% ophthalmic ointment, Gentamicin injection, Gentamicin 3% ophthalmic ointment
    • 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), Cefoxitin injection, Ceftazidime 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
      • Nitroimidazoles: Metronidazole injection
      • Penicillins: Ampicillin/sulbactam injection, Piperacillin/tazobactam injection
      • Tetracyclines: Doxycycline injection
      • Topical (miscellaneous) antibacterials: Mupirocin calcium 2% cream, Mupirocin calcium 2% nasal ointment (unavailable), 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, Fluconazole injection, Griseofulvin oral tablets and suspension
      • Antiparasitic drugs: Chloroquine tablets, Hydroxychloroquine tablets, Pentamidine isethionate
      • Antiviral drugs: Acyclovir injection, Cidofovir injection
    • Vaccines in coninued 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: Bacitracin ophthalmic ointment (in June 2020), Bacitracin injection (in February 2020), 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).

August 2020 Infectious Disease Update

Announcements

  • Sanford Guide recently released a new AUC Dosing Calculator* which uses two serum concentration measurements to determine AUC24, the preferred method for vancomycin dosing for Staph bacteremia, endocarditis and invasive infection pursuant to new guidelines.
  • Sanford Guide is hosting a Virtual Open House from September 22-24, beginning with a COVID-19 Panel Discussion with members of our editorial board. Pre-registration is required.

SARS-CoV-2 / COVID-19

  • Sanford Guide SARS-CoV-2 / COVID-19 material is freely available to all for the course of the pandemic.
  • Guidelines on COVID-19 diagnosis, treatment and management, and infection prevention: IDSA and NIH.
  • Guidelines (available at PMC) for the pharmacological treatment of COVID-19 from the Brazilian Association of Intensive Care Medicine, the Brazilian Society of Infectious Diseases, and the Brazilian Society of Pulmonology and Tisiology (Rev Bras Ter Intensiva 2020;32:166).
  • Remdesivir for severe COVID-19: a clinical practice guideline (BMJ 2020;370:m2924). Available on the BMJ website.
  • Comprehensive review of pathophysiology, transmission, diagnosis and treatment of COVID-19 in JAMA online 10 July 2020 doi:10.1001/jama.2020.12839.
  • Vaccine development pipeline: see COVID-19, Prevention for summary of vaccine development and clinical trials.

New or Updated Treatment Guidelines

  • Full clinical practice guidelines for the treatment of nontuberculous mycobacterial pulmonary disease, from the ATS, ERS, ESCMID, and IDSA (Eur Resp J 2020;56:2000535). The guidelines are available on the journal website.

Practice Pearls

  • Posaconazole has recently been associated with pseudohyperaldosteronism (secondary hypertension, hypokalemia, and sometimes metabolic acidosis). The drug inhibits adrenal 11β-hydroxylase and 11β-hydroxysteroid dehydrogenase type 2, resulting in accumulation of metabolites with mineralocorticoid effects (11-deoxycorticosterone, 11-deoxycortisol) and reduced inactivation of cortisol. This study found a positive correlation between serum posaconazole concentrations and systolic blood pressure and serum 11-deoxycortisol concentrations, and a negative correlation between posaconazole concentrations and serum potassium concentrations. Posaconazole-induced pseudohyperaldosteronism occurred at posaconazole concentrations (median 3.0 μg/mL) lower than previously reported, suggesting that the issue is underrecognized (Clin Infect Dis 2020;70:2593).
  • When considering cephalosporin cross-reactivity with other β-lactams, we often focus only on the R1 side chain. A recent report describes a 17-year-old female who twice experienced anaphylaxis to cefuroxime. Skin prick test results were negative for all antibiotics; intradermal test results, along with R1 and R2 side chain similarity to cefuroxime, are seen below. Provocation tests with oral amoxicillin, oral cefadroxil (different R1 and R2 side chains), and IM ceftriaxone were negative. These data suggest hypersensitivity to cefuroxime and cefotaxime due to similar R2 side chains (Ann Allergy Asthma Immunol 2020;125:101).
    Drug Intradermal test R1 R2
    Ampicillin Negative Different N/A
    Amoxicillin/clavulanate Negative Different N/A
    Benzylpenicillin Negative Different N/A
    Cefazolin Negative Different Different
    Cefotaxime Positive Similar Similar
    Ceftriaxone Negative Similar Different
    Cefuroxime Positive
  • 2,478 TB patients treated with standard firstline drugs (INH, rifampin, PZA, ethambutol) were reviewed for the occurrence of serious adverse effects (SAEs). 407 patients (16.4%) experienced a SAE (most commonly hepatotoxicity, followed by cutaneous reaction, GI intolerance, and arthropathy) that led to drug discontinuation. The most common causative drug was PZA (55.8%), followed by ethambutol (23.3%), rifampin (13.8%), and INH (6.4%). The incidence of SAEs increased with age, and this held true for all individual drugs except rifampin (PLoS ONE 2020;15:e0236109).

Drug Shortages (US)

  • Antimicrobial drugs or vaccines in reduced supply or unavailable (as of August 9, 2020) due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons:
    • New on the list since July 7Cefotetan injection
    • Shortage recently resolvedBacitracin ophthalmic ointment, Daptomycin injection, Griseofulvin oral tablets and suspension, Mupirocin calcium 2% cream (Glenmark)
    • 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), Cefoxitin injection, Ceftazidime injection, Ceftazidime/avibactam 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
      • Nitroimidazoles: Metronidazole injection
      • Penicillins: Ampicillin/sulbactam injection, Piperacillin/tazobactam injection
      • Tetracyclines: Doxycycline injection
      • 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, Fluconazole injection
      • Antiparasitic drugs: Chloroquine tablets, Hydroxychloroquine tablets, Pentamidine isethionate
      • Antiviral drugs: Acyclovir injection, Cidofovir injection
    • Vaccines in coninued 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).

September 2020 Infectious Disease Update

Announcements

  • Sanford Guide is hosting a Virtual Open House from September 22-24, beginning with a COVID-19 Panel Discussion with members of our editorial board. Other sessions include product feedback sessions with Jeb Sanford, use of Sanford Guide in the classroom, enterprise licensing, and more.

SARS-CoV-2 / COVID-19

  • Sanford Guide SARS-CoV-2 / COVID-19 material is freely available to all for the course of the pandemic.
  • 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). The first version of this living guidance focuses on corticosteroids. Available on the BMJ website.
  • Vaccine development pipeline: see COVID-19, Prevention for summary of vaccine development and clinical trials.

New Drug Approvals

  • Nifurtimox* (Lampit), approved by the U.S. FDA for the treatment of Chagas disease (American Trypanosomiasis*), caused by Trypanosoma cruzi, in pediatric patients. Approval is based on serological results from the first part of a double-blind, randomized Phase 3 study conducted in South America; continuation may be contingent upon demonstration of clinical benefit. Recommended dosage (age <18 years): 8-10 mg/kg/day (divided tid) for body weight ≥40 kg; 10-20 mg/kg/day (divided tid) for body weight <40 kg.

New or Updated Treatment Guidelines

  • Clinical practice guidelines for the evaluation, diagnosis, treatment, and prevention of diabetic foot disease, under the leadership of the Jiangsu Medical Association and the Diabetes Society of the Chinese Medical Association (Burns Trauma 2020;8:tkaa017). The guidelines are available at PMC.
  • 2019 update of the European AIDS Clinical Society Guidelines for treatment of people living with HIV version 10.0 (HIV Med 2020 Sept 3 [Epub ahead of print]). The update is available here.

Practice Pearls

  • There continues to be uncertainty about the impact of non-enzyme-inducing antibiotics on the efficacy of hormonal contraceptives. The argument against the existence of an adverse interaction is based largely on small studies that contain one or more flaws in the way the evidence is interpreted. In a recent analysis of 173,073 spontaneous reports submitted to the UK’s Medicines and Healthcare products Regulatory Agency, unintended pregnancies were seven times more commonly reported with non-enzyme-inducing antibiotics compared to control medicines. No increase in secondary outcomes (such as diarrhea) was observed. Given the life-changing nature of an unintended pregnancy, these data support advising women to take extra conceptive precautions during a course of antibiotics, despite recent recommendations to the contrary (BMJ Evid Based Med 2020 Aug 18 [Epub ahead of print]).
  • We normally think of intravenous acyclovir as a drug administered by intermittent infusion. However, the drug exhibits time-dependent pharmacodynamics vs. herpes simplex virus (HSV), which supports administration by continuous infusion. This report describes two cases of confirmed or suspected neonatal HSV encephalitis successfully treated at home with continuous infusion acyclovir (60 mg/kg/day). In both cases, initial treatment with a few days of intermittent acyclovir was followed by administration via continuous infusion to complete 21 days of therapy, allowing for earlier hospital discharge. No treatment-related adverse effects were observed (Pediatr Infect Dis J 2020;39:830).

Drug Shortages (US)

  • Antimicrobial drugs or vaccines in reduced supply or unavailable (as of September 13, 2020) due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons:
    • New on the list since August 9None
    • Shortage recently resolvedBacitracin ophthalmic ointment, Daptomycin injection, Griseofulvin oral tablets and suspension, Mupirocin calcium 2% cream (Glenmark)
    • 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
      • 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
      • Nitroimidazoles: Metronidazole injection
      • Penicillins: Ampicillin/sulbactam injection, Piperacillin/tazobactam injection
      • Tetracyclines: Doxycycline injection
      • 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, Fluconazole injection
      • Antiparasitic drugs: Chloroquine tablets, Hydroxychloroquine tablets, Pentamidine isethionate
      • Antiviral drugs: Acyclovir injection, Cidofovir injection
    • Vaccines in coninued 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).

October 2020 Infectious Disease Update

Announcements

SARS-CoV-2 / COVID-19

  • Sanford Guide SARS-CoV-2 / COVID-19 material is freely available to all for the course of the pandemic.
  • 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). The first version of this living guidance focuses on corticosteroids. Available on the BMJ website.
  • Updated guidance on the management of COVID-19 from a joint American Thoracic Society/European Respiratory Society Task Force (Eur Respir Rev 2020;29:200287). This release updates prior guidance from the Task Force on the pharmacological management of acute COVID-19, including remdesivir, HCQ, and dexamethasone. Available at PMC.
  • Vaccine development pipeline: see COVID-19, Prevention for summary of vaccine development and clinical trials.

New or Updated Treatment Guidelines

  • 2020 updated guidelines on diagnosis, management, and prevention of central venous catheter-related infections in hematology and oncology, by the Infectious Diseases Working Party of the German Society of Hematology and Medical Oncology (Ann Hematol 2020 Sep 30 [Epub ahead of print]). These guidelines update the 2012 release and are available on the journal website.
  • 2020 recommendations from the International Antiviral Society-USA Panel regarding the use of antiretroviral drugs for the treatment and prevention of HIV infection in adults (JAMA 2020 Oct 14 [Epub ahead of print]). These recommendations update the 2018 release.

Practice Pearls from the Recent Literature

  • Population pharmacokinetic modeling suggests that in critically ill patients treated with caspofungin, the standard fixed-dose regimen may achieve inadequate drug exposure in all patients weighing ≥120 kg, over 80% of median-weight (78 kg) patients, and about 25% of lower-weight (≤50 kg) patients. A weight-based dosing regimen (2 mg/kg loading dose, then 1.25 mg/kg q24h) might be more appropriate (Antimicrob Agents Chemother 2020;64: e00905-20).
  • In a large, retrospective cohort study from the UK, macrolide use during the first trimester of pregnancy was associated with an increased risk of any major malformation, and specifically cardiovascular malformations, compared to penicillins. Macrolide prescribing in any trimester was associated with an increased risk of genital malformations (BMJ 2020;368:m331).
  • Penicillins, including piperacillin-tazobactam, delay the elimination of high-dose methotrexate by interfering with renal proximal tubular secretion of MTX. Severe toxicity (renal, neurologic, hepatic, hematologic, dermatologic, GI, pulmonary) may result from concomitant use (J Oncol Pharm Pract 2020 Sept 2 [Epub ahead of print]).
  • Hyponatremia is a known but probably underappreciated adverse effect of TMP-SMX. Natriuresis is thought to be the most likely explanation, although a recent report provides evidence more consistent with SIADH (Medicine 2020;99:e20746).

Drug Shortages (US)

  • Antimicrobial drugs or vaccines in reduced supply or unavailable (as of October 13, 2020) due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons:
    • New on the list since September 13Amphotericin B injection
    • Shortage recently resolvedMetronidazole 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
      • 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: Doxycycline injection
      • 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, Fluconazole injection
      • Antiparasitic drugs: Chloroquine tablets, Hydroxychloroquine tablets, Pentamidine isethionate
      • 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).

November 2020 Infectious Disease Update

Sanford Guide Announcements

SARS-CoV-2 / COVID-19

  • Sanford Guide SARS-CoV-2 / COVID-19 material is freely available to all for the course of the pandemic.
  • IgG1 monoclonal antibody. BamlanivimabFDA EUA (11/9/20) for outpatient use in mild to moderate COVID-19 in adolescents (age >12 yrs and wt > 40 kg) and adults who are at risk of progression to severe disease.
  • 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). The first version of this living guidance focuses on corticosteroids. Available on the BMJ website.
  • Vaccine development pipeline: see COVID-19, Prevention for summary of vaccine development and clinical trials.

New Drug Approvals

  • Inmazeb*, a combination of three monoclonal antibodies (atoltivimab, maftivimab, and odesivimab-ebgn in a 1:1:1 ratio), approved by the US FDA for the treatment of infection caused by Zaire ebolavirus in adult and pediatric patients, including neonates born to a mother who is RT-PCR positive for Zaire ebolavirus infection. Recommended dosage: 50 mg of atoltivimab, 50 mg of maftivimab, and 50 mg of odesivimab per kg IV as a single infusion. Product availability: single-dose vials, 241.7 mg of each antibody per 14.5 mL.

New or Updated Treatment Guidelines

Practice Pearls from the Recent Literature

  • No data on CSF penetration of ceftolozane-tazobactam have previously been available. In ten critically ill patients with an indwelling external ventricular drain, CSF penetration ratios of ceftolozane and tazobactam were both 0.2, and 3 gm IV q8h achieved a >90% probability of target attainment in the CSF only when MICs were ≤0.25 µg/mL. These data suggest inadequate CSF exposure for gram-negative infection using maximal dosing of ceftolozane-tazobactam unless pathogen MICs are very low (Antimicrob Agents Chemother 2020 Oct 19 [Epub ahead of print]).
  • Pharmacokinetic/pharmacodynamic data for minocycline are limited, given that the drug was approved about a half-century ago. In a PK study in 55 patients, IV minocycline (200 mg IV q12h) was predicted to result in a suboptimal PK/PD profile for Acinetobacter baumannii infection with MIC values ≥1 µg/mL (CLSI susceptibility breakpoint ≤4 µg/mL), emphasizing the importance of considering combination therapy when using minocycline for A. baumannii and raising questions about current interpretive breakpoints (Antimicrob Agents Chemother 2020 Nov 9 [Epub ahead of print]).
  • A patient with COVID-19 administered remdesivir (RDV) developed marked sinus bradycardia on day two of treatment (heart rate 38 bpm, baseline 60-70 bpm). No cardiotoxic drugs in her regimen were identified, and her bradycardia was attributed to COVID-19. After two days of persistent bradycardia with eventual QRS complex widening and other cardiac symptoms, RDV was discontinued and atropine administered. Her bradycardia, widened QRS, and other symptoms resolved rapidly, suggesting a possible rare RDV adverse effect (JACC Case Rep 2020 Oct 28 [Epub ahead of print]).
  • Pharmacokinetic changes commonly associated with extracorporeal membrane oxygenation (ECMO) include increased volume of distribution and alterations in drug clearance. Published data regarding caspofungin have been inconclusive, but two recent studies (in critically ill and lung transplant patients) suggest no significant effect of ECMO on caspofungin pharmacokinetics (Antimicrob Agents Chemother 2020;64:e00345-20Antimicrob Agents Chemother 2020 Aug 17 [Epub ahead of print]).
  • Remdesivir (RDV) is not recommended in its EUA for patients with eGFR <30 mL/min in part because the drug vehicle, sulfobutylether-β-cyclodextrin (SBECD), may accumulate to toxic concentrations. However, each 100 mg of lyophilized powder and solution of RDV contain only 3 gm and 6 gm of SBECD, respectively, compared to the maximum recommended safety threshold of 250 mg/kg/day for SBECD. Although conclusive safety data in patients with eGFR <30 mL/min are lacking, the recommended 5-10 day RDV treatment duration and relatively low concentrations of SBECD suggest benefit may outweigh risk, particularly since SBECD is readily removed by hemodialysis and CRRT (J Am Soc Nephrol 2020;31:1384).

Drug Shortages (US)

  • Antimicrobial drugs or vaccines in reduced supply or unavailable (as of November 10, 2020) due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons:
    • New on the list since October 13None
    • Shortage recently resolvedMetronidazole 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
      • 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: Doxycycline injection
      • 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, Pentamidine isethionate
      • 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).

December 2020 Infectious Disease Update

Sanford Guide Announcements

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
    • FDA authorizes emergency use of Pfizer-BioNTech COVID-19 Vaccine on 11 Dec 2020. See COVID-19 Prevention for summary of FDA Provider Fact Sheet / Emergency Prescribing Information.
    • 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). The first version of this living guidance focuses on corticosteroids. Available on the BMJ website.
  • Guidelines on COVID-19 management in cancer patients, from the Infectious Diseases Working Party of the German Society for Hematology and Medical Oncology (Eur J Cancer 2020;140:86). The guidelines are available at PMC.
  • Casirivimab + Imdevimab (administered together). FDA EUA (11/21/20) for treatment of mild to moderate COVID-19 in adults and children (age ≥12 years, wt ≥40 kg) who are at risk of progression to severe disease and/or hospitalization.

Baloxavir Updates

  • In addition to its indication for treatment of acute uncomplicated influenza, baloxavir marboxil is now indicated for post-exposure prophylaxis of influenza in persons 12 years of age and older following contact with an infected person. The dosing is the same as for treatment of acute infection.
  • Also new is a granule form for oral suspension, intended for patients who are unable to swallow tablets. One bottle contains 40 mg of baloxavir marboxil (after reconstitution with 20 mL of water) and must be used within 10 hours.

New or Updated Treatment Guidelines

Practice Pearls from the Recent Literature

  • A pharmacokinetic drug interaction between hydromorphone and rifampin might be unexpected, given the minor role of the CYP450 system in hydromorphone metabolism. In a randomized crossover study of 12 subjects, rifampin reduced the AUC of oral and intravenous hydromorphone by 43% and 26%, respectively. This is similar to the magnitude of the interaction between morphine and rifampin, and may be due to induction of UGT (glucuronidation) enzymes by rifampin (Anesth Analg 2020 Nov 6 [Epub ahead of print]).
  • Appropriate dosing of linezolid in obesity is uncertain. In a prospective pharmacokinetic study in critically ill obese patients (median total body weight 140 kg) with severe skin and soft tissue infections, the probability of PK/PD target attainment with standard dosing  (600 mg q12h) failed to reach ≥90% for organisms with MICs ≥2 µg/mL. These data add to a growing body of evidence that standard dosing of linezolid in obesity may be inadequate (Antimicrob Agents Chemother 2020 Nov 30 [Epub ahead of print]).

Drug Shortages (US)

  • Antimicrobial drugs or vaccines in reduced supply or unavailable (as of December 13, 2020) due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons:
    • New on the list since November 10None
    • Shortage recently resolvedMetronidazole 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
      • 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: Doxycycline injection
      • 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).