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 2019

New Antimicrobial Drug Approvals

• Xenleta (lefamulin*), a systemically-administered pleuromutilin, approved for the treatment of adult with community-acquired pneumonia caused by susceptible strains of S. pneumoniae, MSSA, H. influenzae, L. pneumophila, M. pneumoniae, and C. pneumoniae. Pleuromutilins inhibit bacterial protein synthesis by binding to the peptidyl transferase center of the 50S bacterial ribosome, thereby preventing the binding of tRNA for peptide transfer. Recommended dosage: 150 mg IV q12h x5-7 days (switching to oral therapy to complete the course if appropriate), or 600 mg po q12h x5 days. Product availability: injection, 600 mg tablets.

• Pretomanid* Tablets, a nitroimidazooxazine antimycobacterial drug, approved as part of a combination regimen with bedaquiline and linezolid for the treatment of adults with pulmonary MDR-TB or XDR-TB. Recommended dosage: 200 mg po once daily for 26 weeks (with bedaquiline and linezolid). The combination regimen should be taken with food. Product availability: 200 mg tablets.

Drug Safety Communications

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

From CDC

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

New or Updated Treatment Guidelines

• Clinical practice guidelines for microbiological laboratory testing used in the diagnosis of fungal infections commonly encountered in pulmonary and critical care practice, from the American Thoracic Society (Am J Respir Crit Care Med 2019;200:535). The guidelines are available for download on the journal website.

• Revised guidelines for the management of HHV-6 infections in patients with hematological malignancies and after hematopoietic stem cell transplantation, from the 2017 European Conference on Infectious in Leukemia (Haematologica 2019 August 29 [Epub ahead of print]). The guidelines are available for download on the journal website.

Drug Shortages (US)

• Antimicrobial drugs or vaccines in reduced supply or unavailable (as of August 30, 2019) due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons:
  • [New on the list since August 1]: None
  • [Shortage recently resolved]: Hepatitis A vaccine inactivated, Letermovir tablets
  • [Continue to be in reduced supply]:
    • Aminoglycosides: Amikacin injection, Gentamicin ophthalmic ointment (unavailable), Tobramycin injection
    • Carbapenems: Meropenem injection
    • Cephalosporins: Cefazolin injection, Cefepime injection, Cefotaxime injection (unavailable), Cefoxitin injection, Ceftazidime injection, Ceftriaxone injection, Cefuroxime injection
    • Clindamycin injection
    • Fluoroquinolones: Ciprofloxacin 0.3% ophthalmic solution, Ciprofloxacin oral suspension, Gemifloxacin tablets
    • Glyco-, glycolipo-, lipopeptides: Daptomycin injection, Vancomycin injection
    • Macrolides/azalides: Azithromycin injection, Azithromycin ophthalmic solution 1% (unavailable), Erythromycin lactobionate injection, Erythromycin 0.5% ophthalmic ointment
    • Nitrofurantoin oral suspension
    • Nitroimidazoles: Metronidazole injection
    • Penicillins: Ampicillin/sulbactam injection, Piperacillin/tazobactam injection
    • Tetracyclines: Doxycycline hyclate injection
    • Topical (miscellaneous) antibacterials: Bacitracin ophthalmic ointment (unavailable), Mupirocin calcium 2% cream, Mupirocin calcium 2% nasal ointment (unavailable), Sulfanilamide 15% vaginal cream (unavailable)
    • Antifungal drugs: Clotrimazole 10 mg oral troches, Fluconazole injection, Griseofulvin oral tablets, Nystatin oral suspension
    • Antiparasitic drugs: Pentamidine isethionate
    • Antiretroviral drugs: None
    • Antiviral drugs: Cidofovir injection, Letermovir injection (unavailable)
    • Vaccines: Hepatitis B vaccine recombinant, Zoster vaccine recombinant (Shingrix), Yellow Fever vaccine (YF-VAX is unavailable, but Stamaril can be obtained through a limited number of clinics in the US. Click here).

• Antimicrobial drugs newly discontinued: Quinidine gluconate IV (in December 2017). Product distribution will continue until expiration of current stock (March 2019).
  • Recent discontinuations: Terbinafine granules (in May 2017), MenHibrix (in February 2017), Elvitegravir (Vitekta, in December 2016), Peginterferon alfa-2b (in February 2016; 50 mcg vials still available in limited quantities), Boceprevir (in December 2015), Permethrin 1% topical lotion (in September 2015)

• For detailed information including estimated resupply dates, see http://www.ashp.org/menu/DrugShortages

 
Sperryville, VA – Sanford Guide® announces the availability of its industry-leading infectious diseases guidelines through lab reports generated by Wise Diagnostic Systems. This new integration, facilitated by Sanford Guide’s content delivery API, links to pertinent Sanford Guide content directly from the report to help guide appropriate antimicrobial selection and dosing.
 
Wise Diagnostic Systems, a state-of-the-art molecular laboratory focused on infectious disease testing, offers comprehensive panels that detect a broad range of pathogens and common antibiotic resistance using PCR technology. The new interface with Sanford Guide content ensures clinicians quickly receive accurate results that include the most up to date pathogen information and therapy options for infectious diseases.
 
The Wise Diagnostic Systems interface with Sanford Guide represents the next logical iteration in laboratory diagnostics. By providing accurate and rapid PCR based results coupled with Sanford Guide recommendations, Wise Diagnostic Systems results provide not only clear, concise and actionable lab results, but also the most current antimicrobial therapy guidelines to support sound clinical decisions. “Coupled together, these facilitate better patient outcomes while fostering antibiotic stewardship,” notes Scott Brady, CEO and Founder of Wise Diagnostic Systems.
 
The growth in real-time integrations with Sanford Guide demonstrates the ease with which trusted guidelines can be incorporated into the clinical workflow using the Sanford Guide API. Since releasing the API in 2017, Sanford Guide content has been made available to tens of thousands of practitioners through clinical surveillance platforms and laboratory information systems. Providing information that is accessible, concise, and reliable, the API furthers Sanford Guide’s mission by reducing time-to-answer and providing guidance when it is needed most.
 
About Wise Diagnostic Systems
Veteran owned and operated, Wise Diagnostic Systems offers practical diagnostics to help clinicians achieve better patient outcomes. Through its state-of-the-art laboratory, Wise Diagnostic Systems provides FDA approved molecular testing platforms that achieve better sensitivity and specificity than conventional methodologies. 
 
About Sanford Guide
Since 1969, Sanford Guide has been a leader in point-of-care recommendations for the treatment of infectious diseases. Widely used by pharmacists, physicians, physician assistants, and nurses, Sanford Guide helps to improve patient care by providing carefully curated recommendations based on the latest evidence. Sanford Guide takes pride in responsiveness to customers, the development of innovative solutions, and providing content that is unparalleled in quality and clinical applicability.

 

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 2019

From CDC

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

Practice Pearls

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

  Study arm (seven days per arm, 7 days washout between arms)	Velpatasvir AUC (geometric mean)
  Sofosbuvir/velpatasvir 400/100 mg on day 5 + 250 mL water	3742 mcg*hr/L
  Sofosbuvir/velpastavir 400/100 mg on day 5 + 250 mL water, omeprazole 40 mg qd (days 1-6)	2705 mcg*hr/L
  Sofosbuvir/velpastavir 400/100 mg on day 5 + 250 mL Coca-Cola, omeprazole 40 mg qd (days 1-6)	5981 mcg*hr/L

Drug Shortages (US)

• Antimicrobial drugs or vaccines in reduced supply or unavailable (as of August 1, 2019) due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons:
  • [New on the list since July 17]: Bacitracin ophthalmic ointment, Griseofulvin oral tablets, Letermovir tablets
  • [Shortage recently resolved]: Amphotericin B injection, Nelfinavir tablets, Valganciclovir oral powder for solution
  • [Continue to be in reduced supply]:
    • Aminoglycosides: Amikacin injection, Gentamicin ophthalmic ointment (unavailable), Tobramycin injection
    • Carbapenems: Meropenem injection
    • Cephalosporins: Cefazolin injection, Cefepime injection, Cefotaxime injection (unavailable), Cefoxitin injection, Ceftazidime injection, Ceftriaxone injection, Cefuroxime injection
    • Clindamycin injection
    • Fluoroquinolones: Ciprofloxacin 0.3% ophthalmic solution, Ciprofloxacin oral suspension, Gemifloxacin tablets
    • Glyco-, glycolipo-, lipopeptides: Daptomycin injection, Vancomycin injection
    • Macrolides/azalides: Azithromycin injection, Azithromycin ophthalmic solution 1% (unavailable), Erythromycin lactobionate injection, Erythromycin 0.5% ophthalmic ointment
    • Nitrofurantoin oral suspension
    • Nitroimidazoles: Metronidazole injection
    • Penicillins: Ampicillin/sulbactam injection, Piperacillin/tazobactam injection
    • Tetracyclines: Doxycycline hyclate injection
    • Topical (miscellaneous) antibacterials: Mupirocin calcium 2% cream, Mupirocin calcium 2% nasal ointment (unavailable), Sulfanilamide 15% vaginal cream (unavailable)
    • Antifungal drugs: Clotrimazole 10 mg oral troches, Fluconazole injection, Nystatin oral suspension
    • Antiparasitic drugs: Pentamidine isethionate
    • Antiretroviral drugs: None
    • Antiviral drugs: Cidofovir injection (unavailable), Letermovir injection (unavailable)
    • Vaccines: Hepatitis A vaccine inactivated, Hepatitis B vaccine recombinant, Zoster vaccine recombinant (Shingrix), Yellow Fever vaccine (YF-VAX is unavailable, but Stamaril can be obtained through a limited number of clinics in the US. Click here).
• Antimicrobial drugs newly discontinued: Quinidine gluconate IV (in December 2017). Product distribution will continue until expiration of current stock (March 2019).
  • Recent discontinuations: Terbinafine granules (in May 2017), MenHibrix (in February 2017), Elvitegravir (Vitekta, in December 2016), Peginterferon alfa-2b (in February 2016; 50 mcg vials still available in limited quantities), Boceprevir (in December 2015), Permethrin 1% topical lotion (in September 2015)
• For detailed information including estimated resupply dates, see http://www.ashp.org/menu/DrugShortages

 
Sperryville, VA – Sanford Guide® announces the availability of its industry-leading infectious diseases guidelines through MD Labs® Results Reports. This new integration, facilitated by Sanford Guide’s content delivery API, links to pertinent Sanford Guide content directly from the report to help guide appropriate antimicrobial selection and dosing. “Interpreting lab results within the context of a given therapeutic scenario can be a challenge. Pairing Sanford Guide content with MD Labs’ succinct reports in an interactive and continuously updated format will help clinicians make the right decisions for their patients,” noted Sanford Guide vice president Scott Kelly.
 
MD Labs, an industry leader in clinical diagnostic testing and reporting, delivers Results Reports with interactive Sanford Guide content through its online client portal. Providing services in the areas of clinical toxicology, pharmacogenetics, and molecular diagnostics, MD Labs was founded with the goal of creating a more provider-friendly testing service that prides itself on delivering prompt, accurate, reliable, and easy to understand results. Integration of Sanford Guide content into Results Reports furthers this mission by providing clinicians with actionable guidance on how to act upon test results.
 
Since releasing its content delivery API in 2017, Sanford Guide content has been made available to tens of thousands of practitioners directly within their clinical surveillance and laboratory information systems. Providing information that is accessible, concise, and reliable, Sanford Guide’s API saves valuable time by providing information that is integrated seamlessly within the clinical workflow. The API furthers Sanford Guide’s mission by reducing time-to-answer and providing guidance when it is needed most.
 
About MD Labs
MD Labs was founded in 2011 with the goal bringing new technologies to the laboratory space and serving physicians across the United States. Constantly adding services based on new technologies, Physician requests and pharmacotherapeutic trends allows us to provide quick, accurate, and cost-effective labwork while enhancing overall patient care.
 
About Sanford Guide
Since 1969, Sanford Guide has been a leader in point-of-care recommendations for the treatment of infectious diseases. Widely used by pharmacists, physicians, physician assistants, and nurses, Sanford Guide helps to improve patient care by providing carefully curated recommendations based on the latest evidence. Sanford Guide takes pride in responsiveness to customers, the development of innovative solutions, and providing content that is unparalleled in quality and clinical applicability.
 

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 2019

New Antimicrobial Drug Approvals

• Recarbrio (imipenem/cilastatin/relebactam), approved for patients ≥18 years of age who have limited or no alternative treatment options for complicated urinary tract infections (including pyelonephritis) and complicated intra-abdominal infections. Imipenem is a carbapenem, cilastatin is an inhibitor of renal dehydropeptidase, and relebactam is a beta-lactamase inhibitor. Recommended dosage, normal renal function: 1.25 gm (imipenem 500 mg, cilastatin 500 mg, relebactam 250 mg) IV q6h. Note that the cilastatin is included in the dosage of this product, unlike imipenem/cilastatin.

New or Updated Treatment Guidelines

• Clinical practice guidelines for the management of chronic hepatitis B, from the Korean Association for the Study of the Liver (KASL) (Clin Mol Hepatol 25:93, 2019). These guidelines update the 2015 release and are available on the journal website.

• 2019 European guidelines for the management of lymphogranuloma venereum, from the International Union against Sexually Transmitted Infections (J Eur Acad Dermatol Venereol 2019 June 26 [Epub ahead of print[). These guidelines update the 2013 release and are available on the journal website.

Practice Pearls

• We would not expect drug-drug interactions to be a significant issue with clotrimazole troches, given the poor oral absorption of clotrimazole from that formulation. However, a heart transplant patient receiving everolimus (a CYP3A4 and P-glycoprotein substrate) for rejection prevention and clotrimazole troches 10 mg qid for thrush prophylaxis experienced a sharp drop in everolimus trough concentrations (8.4 to 2.5 ng/mL) following the discontinuation of clotrimazole (calculated oral clearance of everolimus increased from 6.0 to 11.2 L/hr). A similar phenomenon has been observed in patients treated with tacrolimus (also a CYP3A4 and P-gp substrate) and clotrimazole troches, and it may have contributed to graft rejection. In another study, clotrimazole troches reduced the oral clearance of midazolam (a CYP3A4 substrate) without affecting systemic clearance. A plausible explanation is that clotrimazole achieves sufficient intestinal concentrations to inhibit presystemic clearance and thus enhance everolimus bioavailability (by inhibiting intestinal CYP3A4 and/or P-gp), but it achieves insufficient concentrations in the hepatic circulation to inhibit hepatic CYP3A4 and/or P-gp (Br J Clin Pharmacol 2019 June 26 [Epub ahead of print]).

Drug Shortages (US)

• Antimicrobial drugs or vaccines in reduced supply or unavailable (as of July 1, 2019) due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons:
  • [New on the list since June 11]: None
  • [Shortage recently resolved]: Amphotericin B injection, Nelfinavir tablets
  • [Continue to be in reduced supply]:
    • Aminoglycosides: Amikacin injection, Gentamicin ophthalmic ointment (unavailable), Tobramycin injection
    • Carbapenems: Meropenem injection
    • Cephalosporins: Cefazolin injection, Cefepime injection, Cefotaxime injection (unavailable), Cefoxitin injection, Ceftazidime injection, Ceftriaxone injection, Cefuroxime injection
    • Fluoroquinolones: Ciprofloxacin 0.3% ophthalmic solution, Ciprofloxacin oral suspension, Gemifloxacin tablets
    • Glyco-, glycolipo-, lipopeptides: Daptomycin injection, Vancomycin injection
    • Macrolides/azalides: Azithromycin injection, Azithromycin ophthalmic solution 1% (unavailable), Erythromycin lactobionate injection (unavailable), Erythromycin 0.5% ophthalmic ointment
    • Penicillins: Ampicillin/sulbactam injection, Piperacillin/tazobactam injection
    • Tetracyclines: Doxycycline hyclate injection
    • Other antibacterials: Clindamycin injection, Metronidazole injection, Mupirocin calcium 2% cream, Mupirocin calcium 2% nasal ointment (unavailable), Nitrofurantoin oral suspension, Sulfanilamide 15% vaginal cream (unavailable)
    • Antifungal drugs: Clotrimazole 10 mg oral troches, Fluconazole injection, Nystatin oral suspension
    • Antiparasitic drugs: Pentamidine isethionate
    • Antiretroviral drugs: None
    • Antiviral drugs: Cidofovir injection (unavailable), Letermovir injection (unavailable), Valganciclovir oral powder for solution
    • Vaccines: Hepatitis A vaccine inactivated, Hepatitis B vaccine recombinant, Zoster vaccine recombinant (Shingrix), Yellow Fever vaccine (YF-VAX is unavailable, but Stamaril can be obtained through a limited number of clinics in the US. Click here).
• Antimicrobial drugs newly discontinued: Quinidine gluconate IV (in December 2017). Product distribution will continue until expiration of current stock (March 2019).
  • Recent discontinuations: Terbinafine granules (in May 2017), MenHibrix (in February 2017), Elvitegravir (Vitekta, in December 2016), Peginterferon alfa-2b (in February 2016; 50 mcg vials still available in limited quantities), Boceprevir (in December 2015), Permethrin 1% topical lotion (in September 2015)
• For detailed information including estimated resupply dates, see http://www.ashp.org/menu/DrugShortages