Sanford Guide ID Update features current developments in infectious diseases, curated by the Sanford Guide Editorial Board. Links marked with an asterisk (*) provide details to Web Edition subscribers, while all other links are universal. If you received this message from a colleague, subscribe now.

Sanford Guide ID Update features current developments in infectious diseases, curated by the Sanford Guide Editorial Board. Links marked with an asterisk (*) provide details to Web Edition subscribers, while all other links are universal. If you received this message from a colleague, subscribe now.

SEPTEMBER 2020

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 9: None
  • Shortage recently resolved: Bacitracin 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).

Sanford Guide ID Update features current developments in infectious diseases, curated by the Sanford Guide Editorial Board. Links marked with an asterisk (*) provide details to Web Edition subscribers, while all other links are universal. If you received this message from a colleague, subscribe now.
 
Sanford Guide ID Update features current developments in infectious diseases, curated by the Sanford Guide Editorial Board. Links marked with an asterisk (*) provide details to Web Edition subscribers, while all other links are universal. If you received this message from a colleague, subscribe now.
 

AUGUST 2020

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 7: Cefotetan injection
  • Shortage recently resolved: Bacitracin 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).

• 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. If you received this message from a colleague, subscribe now.
 

JULY 2020

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 10: Ceftazidime/avibactam injection
  • Shortage recently resolved: Cefuroxime 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).

• 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. If you received this message from a colleague, subscribe now.
 

JUNE 2020

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

• 2019 Belgian National guidelines for the diagnosis and treatment of gonorrhea in primary care (Acta Clin Belg 2020 June 2 [Epub ahead of print]).
• 2019 Belgian National guidelines for the diagnosis and treatment of syphilis in primary care (Acta Clin Belg 2020 June 6 [Epub ahead of print]).
• Updated 2019 clinical practice guidelines for the management of hepatitis C virus infection, from the Japan Society of Hepatology (Hepatol Res 2020 Apr 28 [Epub ahead of print]).
• Clinical practice guidelines for systemic antifungal prophylaxis in pediatric patients with cancer and hematopoietic stem-cell transplant recipients (J Clin Oncol 2020 May 27 [Epub ahead of print]). The guidelines are available on the journal website.

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 10: Acyclovir injection, Ethambutol tablets, Metronidazole injection
  • Shortage recently resolved: Gentamicin 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).

• 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. If you received this message from a colleague, subscribe now.
 

MAY 2020

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

• Sanford Guide SARS-CoV-2 / COVID-19 material is freely available to all for the course of the pandemic.
• The U.S. FDA (on May 1, 2020) authorized emergency use of Remdesivir for severe, hospitalized COVID-19.
• Analysis of factors in the spread and acceleration of COVID-19 cases in the United States in MMWR 1 May 2020, ePub.
• Latest IDSA guidelines on COVID-19 diagnosis, treatment and management, and infection prevention.
• NIH treatment guidelines.

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 8: Erythromycin 0.5% ophthalmic ointment
  • Shortage recently resolved: Benzylpenicilloyl 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).

• For more detailed information including estimated resupply dates, see https://www.ashp.org/Drug-Shortages/