News

News

October 2, 2017

October ID Update

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 would like to automatically receive our monthly ID Updates by e-mail, subscribe now.
 

OCTOBER 2017

New Drug Approvals

  • Secnidazole* (Solosec) for the single-dose treatment of bacterial vaginosis in adult women. The recommended dosage is a 2 gram packet of granules sprinkled onto applesauce, yogurt, or pudding and consumed within 30 minutes without chewing or crunching the granules.

Newly Available Generics (US)

  • Oseltamivir phosphate oral suspension 6 mg/mL (Nesher Pharmaceuticals), approved September 14.

New Treatment Guidelines

Updated Treatment Guidelines

  • The AASLD-IDSA guidelines for treatement of hepatitis C* have been updated. This update (September 21, 2017) reflects several important developments including the recent approvals of Mavyret* (glecaprevir/pibrentasvir) and Vosevi* (sofosbuvir/velpatasvir/voxilaprevir). While most sections have been updated, the most significant changes have been made in the Initial Treatment of HCV Infection and Retreatment of Persons in Whom Prior Treatment Has Failed sections as well as the Unique Populations sections, which include patients living with HIV, kidney disease, and severe liver disease including those with severe liver dysfunction and those who have had a liver transplant. The updated guidelines are available at HCVguidelines.org, a website developed by the AASLD and the IDSA to provide up-to-date guidance on the treatment of hepatitis C.

Antimicrobial Stewardship

  • In patients with acute respiratory infection, does greater certainly about etiology improve physician prescribing? In a pragmatic, open-label, randomized trial, patients seen in the ED or acute medical unit of a large hospital in the UK were assigned to receive point-of-care testing (POCT) or routine clinical care. POCT consisted of a rapid molecular test for 15 respiratory viruses that provided results within a few hours. No difference was observed in the proportion of patients receiving antibiotics in each group (83%), although more than half the patients in the POCT group received antibiotics before test results were available, and mean duration of antibiotics was also the same in the two groups (about seven days). However, significantly more patients in the POCT group received only one dose of antibiotics than patients in the routine care group (10% vs. 3%), and duration of treatment <48 hours was significantly more common in the POCT group (17% vs. 9%). In addition, mean length of stay was significantly shorter in the POCT group (5.7 vs. 6.8 days), and appropriate antiviral treatment of influenza-positive patients was significantly more common in the POCT group (91% vs. 65%). These beneficial effects might be further enhanced by combining rapid virus detection with other tests, such as procalcitonin (Lancet Respir Med 5:401, 2017).

New Sanford Guide Integration

  • On September 26, Sanford Guide and digital intelligence provider VigiLanz announced a collaboration to integrate Sanford Guide recommendations into VigiLanz’s market-leading clinical intelligence platform. Read the press release.

Practice Pearls

  • Supratherapeutic vancomycin serum concentrations from oral administration. Although we generally think of oral vancomycin as a minimally absorbed drug, it is important to remember that impressive serum concentrations can be achieved in patients with severe intestinal mucosa injury and impaired renal function. In this report, a patient with rectal cancer admitted for sepsis, renal insufficiency (managed with CRRT), and pseudomembranous colitis was treated with oral vancomycin 500 mg every six hours. After four days the serum vancomycin concentration was found to be 30.6 µg/mL. Colonoscopy demonstrated severe damage throughout the large intestine (J Infect Chemother 2017 Sept 8 [Epub ahead of print]).
  • Weakening of tendons due to divalent cation chelation and/or upregulation of collagen-degrading enzymes are possible mechanisms of fluoroquinolone-associated tendinopathy. Although the Achilles tendon is most frequently involved, it is important to appreciate that non-Achilles tendinopathy also occurs. Here are four recently reported cases of musculoskeletal toxicity associated with fluoroquinolone use involving sites of injury not previously reported. The extent to which fluoroquinolone exposure contributed to these injuries cannot be determined from the data provided.

     

    Case 1. A 55-yo male who presented with right lateral thumb pain following a forceful extension and adduction event was found to have disruption of the radial collateral ligament of the thumb at the proximal insertion with significant fluid collection. Six weeks prior to this injury he had been treated with ciprofloxacin 500 twice daily x7 days for gastroenteritis following international travel. He was conservatively managed and the ligament healed in about four months.

     

    Case 2. A 62-yo female presented with a 6-7 month history of right hip pain that she could not relate to any specific event. She was found to have near complete avulsion of the right hamstring tendons from the ischial tuberosity with a large amount of adjacent free fluid. Of note, she had been treated with frequent courses of ciprofloxacin for chronic recurrent diverticulitis and she was also taking corticosteroids that were prescribed after a previous evaluation of her pain. She was conservatively managed with regular follow-up.

     

    Reference for cases 1 and 2: Am J Phys Med Rehabil 2017 Aug 25 [Epub ahead of print]

     

    Case 3. A 60-yo male sustained injury to his left elbow after abruptly stopping on a bicycle. MRI showed complete triceps avulsion with retraction. Three months prior to the injury he had been given a course of levofloxacin around the time of a prostate biopsy. The details of his levofloxacin regimen are not provided.

     

    Case 4. A 47-yo male suffered a left elbow injury competing in judo and was diagnosed with complete triceps avulsion off the olecranon by MRI. He had been treated for epididymitis with ciprofloxacin three months prior to the injury. Again, the details of the fluoroquinolone regimen are not provided.

     

    Reference for cases 3 and 4: Sports Health 9:474, 2017

Drug Shortages (US)

  • Antimicrobial drugs or vaccines in reduced supply or unavailable due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons:
    • [New on the list]: None
    • [Continue to be in reduced supply]:
      • Aminoglycosides: Amikacin injection, Gentamicin injection, Tobramycin injection
      • Cephalosporins: Cefepime, Cefotaxime injection (unavailable), Cefoxitin, Cefpodoxime oral suspension, Ceftazidime, Ceftriaxone, Cefuroxime injection
      • Fluoroquinolones: Ciprofloxacin oral suspension, Ofloxacin 0.3% ophthalmic solution
      • Penicillins: Amoxicillin/clavulanate 1000 mg/62.5 mg ER tablets, Ampicillin/sulbactam, Oxacillin injection, Penicillin G benzathine, Penicillin G benzathine 900,000 units/Penicillin G procaine 300,000 units (Bicillin C-R 900/300), Penicillin G benzathine/Penicillin G procaine 1.2 million units (Bicillin C-R), Penicillin G procaine injection (unavailable), Piperacillin/tazobactam
      • Other antibacterials: Clindamycin injection, Erythromycin lactobionate injection (unavailable), Metronidazole injection, Mupirocin calcium 2% cream, Mupirocin calcium 2% nasal ointment (unavailable), Vancomycin injection
      • Antifungal drugs: Fluconazole injection
      • Antiparasitic drugs: None
      • Vaccines: Hepatitis A Virus Vaccine Inactivated (Vaqta), Hepatitis B vaccine recombinant, Yellow Fever vaccine (unavailable)
    • [Shortage recently resolved]: Albendazole tablets, Tetanus and Diphtheria Toxoids Adsorbed
  • Antimicrobial drugs newly discontinued:
    • Recent discontinuations: Terbinafine granules (in May 2017), MenHibrix (in February 2017), Elvitegravir (Vitekta, in December 2016), Peginterferon alfa-2b (in February 2016; 50 mcg vials still available in limited quantities), Boceprevir (in December 2015), Permethrin 1% topical lotion (in September 2015)
  • For detailed information including estimated resupply dates, see http://www.ashp.org/menu/DrugShortages

September 26, 2017

Press Release – VigiLanz + The Sanford Guide

VigiLanz Becomes First Clinical Intelligence Platform to Integrate
Sanford Guide Infectious Disease Content

 
MINNEAPOLIS, MN and SPERRYVILLE, VA. – (September 26, 2017) – VigiLanz, a digital healthcare intelligence firm, and Antimicrobial Therapy Inc., publisher and developer of The Sanford Guide, announced today an exclusive partnership that brings together the market-leading clinical intelligence platform and the industry’s top digital infectious disease content. Doing so provides VigiLanz users with the critical next step in the clinical surveillance process—access to peer-reviewed recommendations on the latest treatments for improved patient outcomes.
 
The agreement with Sanford Guide, the most trusted name in the treatment of infectious disease, is just the latest in a string of achievements for VigiLanz. Most recently, its antimicrobial stewardship platform achieved the top overall satisfaction rating in the “Antimicrobial Stewardship 2017” performance report from KLAS Research.
 
The VigiLanz clinical intelligence platform leverages real-time monitoring of thousands of patient care data elements to help improve medication safety, antimicrobial stewardship, infection prevention, quality and care management, and patient safety. Its state-of-the-art rules engine analyzes that data and pushes alerts to clinicians at the point of care when interventions and other actions are necessary, driving significant improvements in safety, efficiency, performance, and reimbursement.
 
“Integrating Sanford Guide content into this process answers the question, ‘What’s next in the antimicrobial de-escalation process?’ by giving clinicians and pharmacists convenient access to the latest clinician-designed treatment recommendations without having to exit the VigiLanz system,” said VigiLanz Chairman and CEO Dr. David Goldsteen, MD, MBA. “We are proud to provide our clients with access to The Sanford Guide’s exceptional content and clinical guidance, more so because we are the first and only clinical intelligence platform able to do so.”
 
Trusted by clinicians in more than 100 countries, The Sanford Guide is optimized to minimize time-to-answer while providing comprehensive guidance at the point of care. Edited by distinguished infectious disease experts from leading academic and clinical centers, Sanford Guide content provides comprehensive coverage of treatment options for infectious diseases, syndromes, and pathogens. Under the partnership agreement, VigiLanz clients will have access to the full suite of Sanford Guide digital infectious disease content.
 
With continually updated information based on the latest available evidence, focused anti-infective drug information, interactive dosing tables, and extensive links to references and related resources, The Sanford Guide provides actionable guidance that is accessible, concise, and reliable.
 
“This partnership with VigiLanz is the most unique collaboration our company has undertaken since its founding nearly 50 years ago. As we moved forward with ever more sophisticated digital offerings, it was imperative that the company we aligned with share our values and commitment to improving the quality of treatment through focused clinical guidance at the point of care. VigiLanz was that company,” said Sanford Guide CEO and Managing Editor Jeb Sanford. “Together we have created a product that fully integrates trusted clinical treatment recommendations with top-rated clinical surveillance tools. Our goal is to improve patient outcomes while minimizing technology burdens on providers.”
 
For more information on the VigiLanz-Sanford Guide partnership, visit VigiLanz in booth #226 or Sanford Guide in booth #710 during IDWeek 2017, taking place October 4-8 in San Diego, CA.
 
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. With over 1 million users worldwide, Sanford Guide takes pride in responsiveness to customers, the development of innovative solutions, and providing content that is unparalleled in quality and clinical applicability.
 
About VigiLanz
Founded in 2001, VigiLanz Corporation (www.vigilanzcorp.com) is a privately held, rapidly growing provider of SaaS health care intelligence and predictive analytics. The firm is focused on aggregating disparate EHR transactional workflow and documentation data across health systems to identify real-time clinical issues that avoid or minimize harm, optimize clinical outcomes and support preventive care along the entire health system continuum. VigiLanz supports a large and growing community of hospital CMOs, CMIOs, CIOs, quality teams, infectious disease and control specialists, pharmacists, and other clinicians dedicated to real-time inpatient and outpatient care. VigiLanz is shaping the emerging era of real-time health care by delivering enterprise intelligence technology and services that improve clinical outcomes, patient care and operational effectiveness.

Download the press release.

September 19, 2017

September ID Update

ID Update is The Sanford Guide’s monthly summary of significant developments in the treatment of infectious diseases. Want to receive ID Update by e-mail? Click here to subscribe. We won’t spam you or share your contact information.

Links marked with a “*” are accessible to Sanford Guide Web Edition and Sanford Guide All Access subscribers. Other links are accessible to all users.
 

New Drug Approvals

  • Benznidazole* for the treatment of pediatric patients 2 to 12 years of age with Chagas disease* (American trypanosomiasis), a parasitic infection caused by Trypanosoma cruzi. Recommended dosage: 5-8 mg/kg/day (divided q12h) x60 days.
  • Vabomere (Meropenem + Vaborbactam)* for the treatment of patients ≥18 years of age with complicated urinary tract infection including pyelonephritis caused by E. coli, K. pneumoniae, and E. cloacae. Meropenem is a carbapenem and Vaborbactam is a cyclic boronic acid beta-lactamase inhibitor. Recommended dosage in normal renal function: 4 gm (Meropenem 2 gm/Vaborbactam 2 gm) IV q8h (each dose infused over 3 hr).

Updated Treatment Guidelines

  • The annual report from the Advisory Committee on Immunization Practices (ACIP) regarding the use of influenza* vaccines has been released (MMWR Recomm Rep 2017; 66 [No. RR-2]: 1–20). For the 2017–18 season, inactivated and recombinant influenza vaccine will be available in trivalent and quadrivalent formulations. Live attenuated influenza vaccine is not recommended due to concerns about its effectiveness against (H1N1)pdm09 viruses during the 2013–14 and 2015–16 seasons. No preferential recommendation is made for one vaccine product over another for persons for whom more than one licensed, recommended product is available. The full report is available on the CDC MMWR website.
  • Recommendations from the American Academy of Pediatrics (AAP) for routine use of the seasonal influenza vaccine and antiviral medications for the prevention and treatment of influenza in children have been published online (Pediatrics 2017 Sep 4 [Epub ahead of print]). The AAP recommends that pediatricians offer influenza vaccine to all children 6 months of age and older, as soon as the vaccine becomes available, in order to complete vaccination and provide protection before the flu season starts. The recommendations are available for download on the AAP website.
  • The Guidance for Non-HIV-Specialized Providers Caring for Persons with HIV Displaced by Disasters has been updated. Included are recommendations based on the current standard of care for persons with HIV infection and also specific guidance on management of HIV infection during pregnancy. In addition, the guidance includes an intake form clinicians can use when evaluating a patient with HIV, a collection of web-based resources for information on treatment and prevention of HIV, and a list of temporary regimen substitutions in case of supply shortages. The guidance is available for download on the AIDSinfo website.
  • Updated European guidelines for the management of genital herpes have been published online (Int J STD AIDS 2017 Jan 1 [Epub ahead of print]). The guidelines are available for download on the International Union against Sexually Transmitted Infections (IUSTI) website.
  • Updated guidelines for the diagnosis and empirical treatment of fever of unknown origin in adult neutropenic* patients from the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO) have been published (Ann Hematol 2017 Aug 30 [Epub ahead of print]). These guidelines update the 2003 release and are available for download on the journal website.

Update on Miltefosine

  • CDC is no longer providing Miltefosine* for treatment of free-living amoeba infections (AcanthamoebaBalamuthia, Naegleria). It is commercially available and must be obtained directly from Profounda, Inc. (www.profounda.com).

Practice Pearls

  • With the introduction of meropenem/vaborbactam* there are now five commercially available beta-lactamase inhibitors marketed in combination with a companion antibacterial agent (relebactam is not yet commercially available). Here is a chart of their activities versus the various classes of beta-lactamase enzyme. The letter in parentheses refers to the Ambler beta-lactamase class (the Ambler classification scheme is based on amino acid sequence homology).
TEM/SHV (A) CTX-M (A) KPC (A) MBL (B) AmpC (C) OXA (D)
Clavulanate Yes Yes No No No No
Sulbactam Yes Yes No No No No
Tazobactam Yes Yes No No No No
Avibactam Yes Yes Yes No Yes Yes
Vaborbactam Yes Yes Yes No Yes No
Relebactam Yes Yes Yes No Yes ?

NOTES:

  1. TEM and SHV are common beta-lactamases found in Gram-negative bacteria
  2. The CTX-M family is a type of extended-spectrum beta-lactamase (ESBL)
  3. KPC is Klebsiella pneumoniae carbapenemase
  4. MBL is metallo-beta-lactamase (e.g. IMP, VIM, NDM)
  5. AmpC is the inducible chromosomal beta-lactamase associated with certain Enterobacteriaceae (Serratia, Enterobacter, Aeromonas, Citrobacter, Hafnia, indole-positive Proteus, Morganella, Providencia)
  6. Some OXA enzymes may be inhibited by tazobactam or clavulanate
  7. References: Drugs 77:615, 2017 and Clin Microbiol Rev 23:160, 2010.
  • Inflammatory processes seem to play a role in a variety of psychiatric disorders, and recent data suggest that anti-inflammatory drugs may be useful adjunctive treatment for depression. Could the anti-inflammatory properties of minocycline* be useful in this regard? In a small (n=41), randomized, double-blind, placebo-controlled pilot trial in patients with treatment-resistant major  depressive disorder, minocycline (100 mg qd x2 weeks, then 200 mg qd x10 weeks) was added to existing antidepressant treatment. A large, statistically significant decrease in Hamilton Depression Rating Scale was observed in the minocycline group. Clinical Global Impression score was significantly improved, and other measures showed improvement as well. Minocycline was well tolerated. These preliminary findings require confirmation in larger studies with longer follow-up periods (J Psychopharmacol 2017 Aug 1 [Epub ahead of print]).
  • Oral fosfomycin* is considered a firstline option for uncomplicated cystitis, although it appears to have inferior efficacy compared with other short course regimens. Despite being an “old” drug, our knowledge of its urinary pharmacokinetics is limited. A single 3 gram dose of fosfomycin was administered to 40 healthy females and urine samples were collected for a week. Peak urine concentration was 1982 mcg/mL with considerable intersubject variability (SD 1257). Mean urine Tmax was 7.5 hours, and mean urine half-life was 12.4 hours. High urinary output was correlated with low urine concentrations. It is possible that inadequate drug exposure (resulting from intersubject differences) explains treatment failure in some patients (Clin Microbiol Infect 2017 Aug 31 [Epub ahead of print]).

Drug Shortages (US)

  • Antimicrobial drugs or vaccines in reduced supply or unavailable due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons:
    • [New on the list]: Cefpodoxime oral suspension
    • [Continue to be in reduced supply]:
      • Aminoglycosides: Amikacin injection, Gentamicin injection, Tobramycin injection
      • Cephalosporins: Cefepime, Cefotaxime injection (unavailable), Cefoxitin, Ceftazidime, Ceftriaxone, Cefuroxime injection
      • Fluoroquinolones: Ciprofloxacin oral suspension, Ofloxacin 0.3% ophthalmic solution
      • Penicillins: Amoxicillin/clavulanate 1000 mg/62.5 mg ER tablets, Ampicillin/sulbactam, Oxacillin injection, Penicillin G benzathine, Penicillin G benzathine 900,000 units/Penicillin G procaine 300,000 units (Bicillin C-R 900/300), Penicillin G benzathine/Penicillin G procaine 1.2 million units (Bicillin C-R), Penicillin G procaine injection (unavailable), Piperacillin/tazobactam
      • Other antibacterials: Clindamycin injection, Erythromycin lactobionate injection (unavailable), Metronidazole injection, Mupirocin calcium 2% cream, Mupirocin calcium 2% nasal ointment (unavailable), Vancomycin injection
      • Antifungal drugs: Fluconazole injection
      • Antiparasitic drugs: None
      • Vaccines: Hepatitis A Virus Vaccine Inactivated (Vaqta), Hepatitis B vaccine recombinant, Yellow Fever vaccine (unavailable)
    • [Shortage recently resolved]: Albendazole tablets, Tetanus and Diphtheria Toxoids Adsorbed
  • Antimicrobial drugs newly discontinued: No recent discontinuations
    • Recent discontinuations: MenHibrix (in February 2017), Elvitegravir (Vitekta, in December 2016), Peginterferon alfa-2b (in February 2016; 50 mcg vials still available in limited quantities), Boceprevir (in December 2015), Permethrin 1% topical lotion (in September 2015)
  • For detailed information including estimated resupply dates, see http://www.ashp.org/menu/DrugShortages
August 9, 2017

August ID Update

ID Update is The Sanford Guide’s monthly summary of significant developments in the treatment of infectious diseases. Want to receive ID Update by e-mail? Click here to subscribe. We won’t spam you or share your contact information.

Links marked with a “*” are accessible to Sanford Guide Web Edition and Sanford Guide All Access subscribers. Other links are accessible to all users.

 

New Drug Approvals

  • Mavyret*, a fixed-dose combination of glecaprevir 100 mg (NS3/4A protease inhibitor) and pibrentasvir 40 mg (NS5A inhibitor), for the treatment of adult patients with chronic HCV genotype 1, 2, 3, 4, 5, or 6 infection without cirrhosis and with compensated cirrhosis (Child-Pugh A). The combination is also indicated for the treatment of adult patients with genotype 1 infection who have previously been treated with a regimen containing either an NS5A inhibitor or an NS3/4A protease inhibitor (but not both).

  • Vosevi*, a fixed-dose combination of sofosbuvir 400 mg (NS5B RNA polymerase inhibitor), velpatasvir 100 mg (NS5A inhibitor), and voxilaprevir 100 mg (NS3/4A protease inhibitor), for the treatment of adult patients with chronic HCV infection without cirrhosis or with compensated cirrhosis (Child-Pugh A) who have:

    • genotype 1, 2, 3, 4, 5, or 6 infection and have previously been treated with a regimen containing an NS5A inhibitor.
    • genotype 1a or 3 infection and have previously been treated with a regimen containing sofosbuvir without an NS5A inhibitor.

Treatment Guidelines

  • Brazilian guidelines for the diagnosis and treatment of cystic fibrosis have been published. The guidelines were prepared in partnership with several Brazilian medical societies and received contributions from multiple Brazilian professionals involved in the care of CF patients (J Bras Pneumol 43:219, 2017).

  • Brazilian guidelines for the clinical management of paracoccidioidomycosis have been published. These guidelines update the first Brazilian consensus on paracoccidioidomycosis by providing evidence-based recommendations for bedside management (Rev Soc Bras Med Trop 2017 July 20 [Epub ahead of print].

Antimicrobial Stewardship

  • A provocative analysis in BMJ calls into question our standard instruction to patients to complete the entire prescribed course of antibiotics in hopes of lessening or preventing antibiotic resistance (and treatment failure). There is value in a clear and simple message, but it deserves reassessment.

    In some pathogens such as M. tuberculosis, N. gonorrhoeae, and HIV, genetic mutations conferring resistance may arise spontaneously and be selected for during treatment if dosing is inadequate or monotherapy is employed (the authors term this “target selected resistance”). But for other problematic bacteria such as S. aureus, Enterococcus, Klebsiella, Acinetobacter, and Pseudomonas (all opportunistic microbes that are present in the human gut, on skin and mucus membranes, and in the environment), the predominant driver of resistance is “collateral selection.” When antibiotics are taken for any reason, the pressure leads to antibiotic-susceptible strains being replaced by resistant strains. The longer the antibiotics are taken, the greater the pressure. These resistant strains are often transmitted to asymptomatic persons, or the genetic material conferring resistance can be passed to other bacteria.

    Recommended durations of therapy are generally based on limited evidence and probably, in most cases, do not represent the minimum effective length. At the time they were set there was more concern about undertreating the patient than overusing the drug. Recent trials, however, have already led to shorter durations of therapy for some infections such as community-acquired pneumonia, nosocomial pneumonia, and pyelonephritis. The situation is complicated by newer drugs with different pharmacologic properties, such as longer half-lives, and it is also important to note that patients respond differently to the same antibiotic. A reasonable conclusion is this: we should continue to aggressively conduct research into administering the shortest course of antibiotics possible for all infections (BMJ 358:j3418, 2017).

New Sanford Guide Release

  • In July, the Sanford Guide to HIV/AIDS Therapy 2017 print edition was released in pocket-size and larger-print library editions. This latest guide includes the latest fixed-dose combination and once-daily formulations of ARV drugs, updated differential diagnosis of related syndromes and OIs, and more.

Practice Pearls

  • Optic neuropathy is a serious complication of ethambutol* therapy. At a dose of ≤15 mg/kg/day the risk is <1%, but higher ethambutol doses are associated with substantially increased risk. Other risk factors include age >65, hypertension, the presence of renal disease, and possibly the concomitant use of isoniazid. Visual symptoms develop in most patients within the first nine months of treatment, although they can occur much faster than that; patients experience loss of visual acuity and abnormal color vision, and also central or cecocentral scotoma. The best treatment is primary prevention, which means baseline followed by regular screening (e.g. monthly in high-risk patients). If detected early with prompt drug discontinuation, about 30-60% of patients will show improvement over a period of several months although few will have full recovery. Ethambutol, a metal chelator, impedes mycobacterial cell wall synthesis by inhibiting arabinosyltransferase; chelation of copper or zinc is thought to play an important role in the pathogenesis of optic neuropathy. Zinc or copper supplementation has not been shown to reduce the likelihood of optic neuropathy, however (Curr Opin Ophalmol 2017 Jul 28 [Epub ahead of print].
  • One of the most serious, although usually reversible, neurotoxic effects associated with metronidazole* is encephalopathy. The mechanism of metronidazole-induced encephalopathy, or its relationship to cumulative metronidazole dose or treatment duration, is not clear. It is interesting that the symptoms and brain MRI findings of metronidazole-induced encephalopathy can be similar to those of acute Wernicke’s encephalopathy, a neurologic disorder induced by thiamine deficiency. Given that metronidazole metabolites inhibit thiamine pyrophosphokinase, it is possible that the resulting thiamine antagonism plays a key role in the pathogenesis of metronidazole-induced encephalopathy. It is currently unknown if thiamine supplementation, particularly in thiamine-deficient patients, is a useful treatment strategy (J Neurol Sci 379:324, 2017).

  • Moxifloxacin* is an option for treatment of drug-susceptible tuberculosis when a first-line drug is not tolerated, or for isoniazid monoresistance. It is also being investigated in treatment-shortening regimens for drug-susceptible tuberculosis. We know that adequate antituberculous drug concentrations in the blood and at the infection site(s) are important for maximizing treatment outcomes. The optimal dose of moxifloxacin for tuberculosis has not been firmly established, for at least three reasons: one, drug exposure resulting from standard 400 mg once-daily dosing may not be optimal for efficacy, prevention of resistance, or achieving proposed PK/PD targets; two, the coadministration of rifamycin drugs (e.g rifampin, rifapentine) decreases moxifloxacin Cmax and AUC up to 31%; and three, moxifloxacin distributes heterogeneously in tissues and granulomatous lesions, contributing to substantial interpatient variability in pharmacokinetics. Higher-than-standard doses of moxifloxacin may be necessary to maximize treatment outcomes, but further research is necessary (J Clin Pharmacol 2017 July 24 [Epub ahead of print]).

Drug Shortages (US)

  • Antimicrobial drugs or vaccines in reduced supply or unavailable due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons:

    • [New on the list]: No new antimicrobial shortages

    • [Continue to be in reduced supply]:

      • Aminoglycosides: Amikacin injection, Gentamicin injection, Tobramycin injection

      • Cephalosporins: Cefepime, Cefotaxime injection (unavailable), Cefoxitin, Ceftazidime, Ceftriaxone, Cefuroxime injection

      • Fluoroquinolones: Ciprofloxacin oral suspension, Ofloxacin 0.3% ophthalmic solution

      • Penicillins: Amoxicillin/clavulanate 1000 mg/62.5 mg ER tablets, Ampicillin/sulbactam, Oxacillin injection, Penicillin G benzathine, Penicillin G benzathine 900,000 units/Penicillin G procaine 300,000 units (Bicillin C-R 900/300), Penicillin G benzathine/Penicillin G procaine 1.2 million units (Bicillin C-R), Penicillin G procaine injection (unavailable), Piperacillin/tazobactam

      • Other antibacterials: Clindamycin injection, Erythromycin lactobionate injection (unavailable), Metronidazole injection, Mupirocin calcium 2% cream, Mupirocin calcium 2% nasal ointment (unavailable), Vancomycin injection

      • Antifungal drugs: Fluconazole injection

      • Antiparasitic drugs: Albendazole tablets (unavailable)

      • Vaccines: Hepatitis A Virus Vaccine Inactivated (Vaqta), Hepatitis B vaccine recombinant, Tetanus and Diphtheria Toxoids Adsorbed, Yellow Fever vaccine

  • [Shortage recently resolved]: Tigecycline injection

  • Antimicrobial drugs newly discontinued:
    • Recent discontinuations: MenHibrix (in February 2017), Elvitegravir (Vitekta, in December 2016), Peginterferon alfa-2b (in February 2016; 50 mcg vials still available in limited quantities), Boceprevir (in December 2015), Permethrin 1% topical lotion (in September 2015)

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

July 19, 2017

July ID Update

ID Update is The Sanford Guide’s monthly summary of significant developments in the treatment of infectious diseases. Want to receive ID Update by e-mail? Click here to subscribe. We won’t spam you or share your contact information.

Links marked with a “*” are accessible to Sanford Guide Web Edition and Sanford Guide All Access subscribers. Other links are accessible to all users.

 

New Drug Approval

  • Delafloxacin* (Baxdela), the first new fluoroquinolone antibiotic in many years, was approved by the US FDA in late June. It is indicated for the treatment of adults with acute bacterial skin and skin structure infections caused by designated susceptible bacteria, including MRSA. The recommended dosage is 300 mg IV q12h or 450 mg po q12h x5-14 days. Product availability: 450 mg tablets, injection.

Updated Treatment Guidelines

  • Updated clinical practice guidelines for the management of hepatitis B virus infection from the European Association for the Study of the Liver have been published (J Hepatol 67:370, 2017). These guidelines update the 2012 release and are available for download on the EASL website.

Antimicrobial Stewardship

  • We know that antibiotic stewardship programs reduce antibiotic use and hospital costs. According to the results of a 32-study meta-analysis, they also reduce the incidence of infection and colonization with multidrug-resistance gram-negative bacteria, ESBL-producing gram-negative bacteria, and MRSA, as well as the incidence of C. difficile infection, in hospital inpatients. No effect on the incidence of VRE, or fluoroquinolone-resistant and aminoglycoside-resistant gram-negative bacteria, was observed. Stewardship programs are more effective when implemented in hematology-oncology settings and with infection control strategies such as improved hand hygiene (Lancet Infect Dis 2017 June 16 [Epub ahead of print]).

Practice Pearls

  • According to the latest guidelines from the American Academy of Dermatology, systemic antibiotics are not to be used for mild acne vulgaris*. Systemic antibiotics are reasonable for moderate to severe cases, but only in combination with one or more topical agents. Doxycycline and minocycline are more effective than tetracycline, and azithromycin should only be used if a tetracycline is contraindicated. Other systemic drugs should be avoided due to resistance concerns (such as erythromycin) or lack of supportive data (Am Fam Phys 95:740, 2017J Am Acad Dermatol 74:945, 2016).
  • Phenazopyridine, useful for the relief of pain, burning, and discomfort in patients with UTI, is a commonly used OTC drug that is not without toxicity. Adverse effects include gastrointestinal disturbances, discoloration of urine and skin, hepatitis, hemolytic anemia, methemoglobinemia, and acute tubular necrosis. Added to the list of phenazopyridine toxicities is a case report of biopsy-proven acute interstitial nephritis. The patient’s renal function improved after stopping the phenazopyridine, worsened when it was reintroduced, and improved again after drug discontinuation plus a brief tapering course of oral corticosteroids (Ren Fail 36:804, 2014).
  • Pyrazinamide, an excellent sterilizing agent, is the only antituberculous drug with bactericidal activity against M. tuberculosis in acidic environments. The currently recommended dose is 20-25 mg/kg/day. Using proposed therapeutic targets of Cmax >35 μg/mL and/or AUC of >363 μg x hr/mL, recent pharmacokinetic data suggest that this dose may be too low for most patients. Mathematical simulations suggest that a daily dose in the range of 30-40 mg/kg or more is needed to achieve the therapeutic target(s) in most patients (Antimicrob Agents Chemother 61:e02625, 2017).
  • Extracorporeal membrane oxygenation (ECMO) may result in increased extraction of highly lipophilic and protein-bound drugs, increased volume of distribution (Vd), and altered clearance. The best published pharmacokinetic data are in neonates, although the trials were largely conducted in the 1980s and 1990s. The most well-defined effect of ECMO in neonates is increased Vd, resulting in the need for higher initial doses of some drugs. In contrast, limited studies of poor quality suggest that Vd and clearance are typically unchanged in adults and thus, there are very few recommendations for dose adjustments in that patient population (Clin Ther 38:1976, 2016).
  • Syphilis during pregnancy* is the classic situation in which desensitization of a patient with evidence of IgE-mediated penicillin allergy is necessary. Repeated administration of subthreshold doses of penicillin is thought to provide sufficient antigenic determinant to bind IgE on the surface of basophils and mast cells without cross-linking, thus rendering them unresponsive to higher doses. Oral penicillin desensitization protocols are generally preferred, although GI absorption may be variable; parenteral administration offers the advantage of easier dosage control and the ability to quickly interrupt a dose if a reaction occurs. Allergic reactions, mostly mild, occur in at 1/3 or more of patients undergoing penicillin desensitization but are typically managed successfully with medications and a temporary pause of the desensitization protocol. Following desensitization, subsequent penicillin doses must be given without interruption; if enough doses are missed that the drug has been cleared from the system, or if penicillin is needed again in the future, then the desensitization procedure must be repeated (Ann Allergy Asthma Immunol 118:537, 2017).

Drug Shortages (US)

  •  Antimicrobial drugs or vaccines in reduced supply or unavailable due to increased demand, manufacturing delays, product discontinuation by a specific manufacturer, or unspecified reasons:
    • [New on the list]: No new antimicrobial shortages
    • [Continue to be in reduced supply]:
      • Aminoglycosides: Amikacin injection, Gentamicin injection, Tobramycin injection
      • Cephalosporins: Cefepime, Cefotaxime injection (unavailable), Cefoxitin, Ceftazidime, Ceftriaxone, Cefuroxime injection
      • Fluoroquinolones: Ciprofloxacin oral suspension, Ofloxacin 0.3% ophthalmic solution
      • Penicillins: Amoxicillin/clavulanate 1000 mg/62.5 mg ER tablets, Ampicillin/sulbactam, Oxacillin injection, Penicillin G benzathine, Penicillin G benzathine 900,000 units/Penicillin G procaine 300,000 units (Bicillin C-R 900/300), Penicillin G benzathine/Penicillin G procaine 1.2 million units (Bicillin C-R), Penicillin G procaine injection (unavailable), Piperacillin/tazobactam
      • Other antibacterials: Clindamycin injection, Erythromycin lactobionate injection (unavailable), Metronidazole injection, Mupirocin calcium 2% cream, Mupirocin calcium 2% nasal ointment (unavailable), Vancomycin injection
      • Antifungal drugs: Fluconazole injection
      • Antiparasitic drugs: Albendazole tablets (unavailable)
      • Vaccines: Hepatitis A Virus Vaccine Inactivated (Vaqta), Hepatitis B vaccine recombinant, Tetanus and Diphtheria Toxoids Adsorbed, Yellow Fever vaccine
    • [Shortage recently resolved]: Rabies vaccine (RabAvert)
  • Antimicrobial drugs newly discontinued: No recent discontinuations
    • Recent discontinuations: 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

Sanford Guide Digital Feature Highlights

  • Caring for a patient with fever who has just returned from abroad? Our page on Fever in Returning Travelers* can help!
  • Colistin* dosing. Check out our newly updated colistin dosing calculator*. This interactive tool provides dose recommendations in terms of colistin base activity (mg or IU) or colistimethate (mg or IU) using new clinician-friendly creatinine clearance level-based dosing algorithms (Clin Infect Dis 64:565, 2017) as well as current dose recommendations from the European Medicines Agency. Access the calculator from the Colistin page, from Tables and Tools >> Calculators, or using Search Site.