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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.
June 12, 2017

June 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*, the first new fluoroquinolone antibiotic in many years, was approved by the U.S. FDA in late June. The drug is indicated for acute bacterial skin and skin structure infections caused by gram positive organisms, including MRSA, and gram negative organisms. Both oral and IV formulations are available.

New Dosage Form Approval

  • Ritonavir* (Norvir) oral powder, 100 mg packet, for use in combination with other antiretroviral agents for the treatment of pediatric patients with HIV-1 infection.

Updated Treatment Guidelines

  • The tuberculosis* section of the Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents has been updated. In this revision, the epidemiology, diagnosis, and treatment sections for latent TB infection and TB disease are updated to include more recent statistics, diagnostic tests, and data regarding treatment. In addition, Tables 1-3 of the Guidelines have been updated to include preferred and alternative treatment regimens, and drug-drug interactions with commonly used medications. The guidelines are available for download on the AIDSinfo website.

Practice Pearls

  • The Advisory Committee on Immunization Practices (ACIP) has updated its recommendations regarding the use of MenB-FHbp serogroup B vaccine. MenB-FHbp (Trumenba) is one of two serogroup B vaccines currently licensed in the US for persons 10-25 years of age (the other one is MenB-4C (Bexsero). The vaccines are not interchangeable (a vaccine series must be completed using the same product) and the ACIP does not indicate a product preference. The minimum interval between any two doses of MenB vaccine is four weeks.
     
    The updated recommendations replace previous ACIP recommendations published in 2015. For persons at increased risk for meningococcal disease (e.g., persons with persistent complement component deficiencies, anatomic or functional asplenia, or microbiologists who are routinely exposed to isolates of N. meningitidis) and for use during outbreaks of serogroup B meningococcal disease, ACIP recommends that three doses of MenB-FHbp be administered at 0, 1-2, and 6 months. For healthy adolescents who are not at increased risk for meningococcal disease, two doses administered at 0 and 6 months are recommended. ACIP recommendations regarding the use of MenB-4C have not changed (MMWR 66:509, 2017).
  •  

  • Why is Candida krusei* intrinsically resistance to fluconazole*?
     
    Candida employs four main mechanisms of resistance to azoles: 1) active efflux pumps belonging either to the ATP-binding cassette (ABC) family of transporters or the major facilitator superfamily of transporters, 2) alteration of the target site, lanosterol 14α-demethylase (also known as Erg11p or Cyp51p), via mutations in its encoding gene ERG11, 3) increased expression of the target site, and 4) development of bypass pathways that replace ergosterol (depleted by azoles) with another functional product (Clin Infect Dis 46:120, 2008).
     
    As of now, the mechanism is incompletely understood. The original explanation for fluconazole resistance in C. krusei was the second mechanism above: reduced susceptibility of Erg11p to inhibition by fluconazole compared to Erg11p proteins of other Candida species (Antimicrob Agents Chemother 42:2645, 1998). However, more recent work has shown that efflux pumps also play a role to some degree, such as the ABC transporter Abc1p (Antimicrob Agents Chemother 53:354, 2009). Upregulation of ABC transporters is thought to explain intrinsic fluconazole resistance in C. glabrata. In support of the role of efflux pumps in C. krusei is an interesting study in which the calcineurin inhibitor tacrolimus was shown to reverse the intrinsic resistance of C. krusei to fluconazole in vitro, possibly by acting as an inhibitor of Abc1p (FEMS Yeast Res 14:808, 2014). It is likely that the mechanism of fluconazole resistance in C. krusei is a combination of poor affinity of Erg11p for fluconazole coupled with efflux pump activity.
  •  

  • What is the story behind pyridoxine supplementation of isoniazid* (INH)?
     
    Vitamin B6, erroneously thought to be synonymous with pyridoxine, is actually six substances of equal potency: pyridoxine, pyridoxal, pyridoxamine, and the monophosphate of each. The active form in humans is pyridoxal phosphate. Pyridoxal phosphate is required by at least one hundred enzymes in humans. Important functions of these enzymes include amino acid synthesis, neurotransmitter synthesis (such as epinephrine, dopamine, serotonin, and GABA), hemoglobin manufacture, and the conversion of tryptophan to niacin, to name a few. Rich dietary sources of vitamin Binclude meats, grains, fish, eggs, and carrots; it is found as pyridoxine in vegetables and as pyridoxal or pyridoxamine in animal products. An adequate diet contains 1.5-2 mg per day.
     
    INH was introduced into clinical practice in the early 1950s. By 1953, reports of peripheral neuropathy were appearing in the medical literature. Numbness and tingling of the extremities in a “stocking-glove” pattern, more severe in the feet than in the hands, was observed, followed by more severe symptoms in untreated patients. The similar clinical appearance to vitamin B6 deficiency suggested the possibility of a vitamin B6 deficiency state existing in patients treated with INH, which was supported by subsequent biochemical investigations. Clinical data supporting the value of pyridoxine supplementation for preventing INH-induced peripheral neuropathy began appearing in the literature in the late 1950s (Tubercle 61:191, 1980).
     
    Functional vitamin B6 deficiency is the probable mechanism of INH-induced peripheral neuropathy. There are at least two mechanisms. First, INH and metabolites bind directly to and inactivate pyridoxine species. Second, INH inhibits the enzyme pyridoxine phosphokinase, an enzyme necessary to convert pyridoxine to pyridoxal phosphate. In the current ATS/CDC/IDSA practice guidelines for drug-susceptible tuberculosis, pyridoxine 25-50 mg po qd is recommended along with INH for all persons at risk of neuropathy (e.g., pregnant or nursing women, breastfeeding infants, persons with INH, patients with diabetes, alcoholism, malnutrition, or chronic renal failure, or patients of advanced age). For patients with peripheral neuropathy, the dose should be increased to 100 mg po qd (Clin Infect Dis 63:e147, 2016).
  •  

  • Multiple factors influence cerebrospinal fluid (CSF) drug concentrations including molecular weight, plasma protein binding, hydrophobicity, and affinity for transport mechanisms. Vancomycin* penetration into the CSF is widely believed to be poor, with CSF:serum ratios in the range of 7-30% depending on the reference source. When vancomycin is used to treat bacterial meningitis, a target serum trough concentration of 15-20 μg/mL is believed to help compensate for limited drug penetration.
     
    New data suggest that CSF concentrations of vancomycin may be better than we think. In a recent review of the literature, thirteen studies evaluating serum and CSF concentrations of intravenous vancomycin were identified for further analysis. Studies that included pediatric patients or patients administered intrathecal or intraventricular vancomycin were excluded. Overall, the vancomycin CSF:serum ratio varied from 0 to 81%. Stratified by disease, penetration ranged from 6-81% in meningitis, 5-17% in ventriculitis patients, 0-36% in patients with other infections, and 0-13% in uninfected patients. Clinical cure rates in these studies were 83% of meningitis patients and all the ventriculitis patients, but no clear relationship between CSF concentration and bacteriologic or clinical cure was identified. Perhaps the best description of vancomycin penetration, as suggested by the authors, is not universally low but highly variable (Clin Pharmacokinet 2017 May 20 [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]: Albendazole tablets, Cefotaxime injection (unavailable), Fluconazole injection, Hepatitis B vaccine recombinant, Metronidazole injection
    • [Continue to be in reduced supply]:
      • Aminoglycosides: Amikacin injection, Gentamicin injection, Tobramycin injection
      • Cephalosporins: Cefepime, 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 antimicrobials: Clindamycin injection, Erythromycin lactobionate injection, Mupirocin calcium 2% cream, Mupirocin calcium 2% nasal ointment (unavailable), Vancomycin injection
      • Vaccines: Hepatitis A Virus Vaccine Inactivated, Rabies vaccine (RabAvert), Tetanus and Diphtheria Toxoids Adsorbed, Yellow Fever vaccine
    • [Shortage recently resolved]: Cefotetan injection
  • 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
May 11, 2017

May ID Update

CDC Health Alert Network #401

  • CDC has identified an increase in Shigella* isolates in the US with elevated MIC values (0.12-1 μg/mL) for ciprofloxacin*. These isolates likely have a quinolone resistance gene that may lead to clinically significant reduced susceptibility to fluoroquinolone antibiotics. Current CLSI interpretive criteria categorize isolates with a ciprofloxacin MIC of ≤1 μg/mL as susceptible to ciprofloxacin. This Health Advisory outlines new recommendations for diagnosis, management, and reporting of Shigella with possible reduced susceptibility to ciprofloxacin.

Updated Treatment Guidelines

  • Updated guidelines for the use of antiretroviral agents in pediatric HIV infection* from the HHS Panel on Antiretroviral Therapy and Medical Management of Children Living with HIV are available for download off the AIDSinfo website.
  • Updated guidelines for the management of fever and neutropenia in children with cancer and hematopoietic stem-cell transplantation recipients have been published (J Clin Oncol 2017 May 1 [Epub ahead of print]). These guidelines update the 2012 release and are available for download on the JCO website.
  • The last version of the CDC Guideline for Prevention of Surgical Site Infection was published in 1999. Most recommendations were based on expert opinion. CDC has updated that version using a modified Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach (JAMA Surg 2017 May 3 [Epub ahead of print]). The updated guidelines are available for download on the JAMA Surgery website.

Practice Pearls

  • The currently recommended formulation of amoxicillin-clavulanate* for acute otitis media* (AOM) contains the two components in a 14:1 ratio. The trend in commercially available products has been to increase this ratio to provide improved efficacy of amoxicillin against penicillin-nonsusceptible S. pneumoniae while reducing the dose of clavulanate, thereby reducing the incidence of diarrhea while maintaining activity against H. influenzae and M. catarrhalis. The lowest quantity of clavulanate that will provide effective beta-lactamase inhibition has not been determined. In a small, open-label, nonrandomized study, 40 children (age 6-23 months) were treated with a novel 28:1 product (90 mg/kg/day amoxicillin component x10 days). No difference in protocol-defined diarrhea, diaper dermatitis, or AOM clinical response was observed compared to historical controls receiving the standard 14:1 regimen. 72 children were then treated with the 28:1 product at a reduced dosage (80 mg/kg/day amoxicillin component x10 days); a lower (but not statistically significant) reduction in protocol-defined diarrhea and a significantly lower rate of diaper dermatitis was observed compared to historical controls, again with no apparent reduction in clinical efficacy. Pharmacokinetic findings are also presented. These intriguing results await validation in a larger randomized clinical trial (Antimicrob Agents Chemother 2017 Apr 24 [Epub ahead of print]).
  • For treatment of acute pyelonephritis* the current IDSA recommendation is 5-7 days of a fluoroquinolone (ciprofloxacin or levofloxacin, treatment duration depending on the specific choice) or 14 days of TMP-SMX. In this multicenter, retrospective study, 272 women (≥16 years of age) with pyelonephritis were treated with 7 days of TMP-SMX (n=191) or 7 days of ciprofloxacin (n=81). In an adjusted model, the likelihood of a recurrent UTI within 30 days for the two groups was similar. Fewer women treated with TMP-SMX were bacteremic with E. coli or were hospitalized. These data suggest that for pyelonephritis, 7 days of TMP-SMX may be as effective as 7 days of ciprofloxacin. Clinical validation requires a randomized controlled trial (Am J Med 2017 Feb 16 [Epub ahead of print]).
  • For over 60 years the standard duration of treatment with penicillin for acute streptococcal pharyngitis* has been 10 days. A fascinating investigation into the history of this duration shows that it simply evolved over time in an era much different than today. No therapeutic trials have verified the need for 10 days of penicillin to prevent acute rheumatic fever. The decreasing incidence of rheumatic fever in developed countries, the increasing failure rates for streptococcal eradication with penicillin, and the evidence for equivalent streptococcal eradication rates with short-course regimens (mainly cephalosporins) have failed to alter our faithful devotion to 10 days of penicillin for streptococcal pharyngitis. The practice has the longest lineage of any antimicrobial recommendation in clinical infectious disease and seems to be, as the author puts it, an example of “a more generalized phenomenon in clinical medicine, the fierce inertia of established usage” (Pediatr Infect Dis J 36:507, 2017).
  • Obesity is a common co-morbidity among patient with skin and soft tissue infections (SSTIs). The pharmacokinetics and pharmacodynamics of antibiotics used for the prevention and treatment of SSTIs are altered in obesity, often in a complex manner. A specific question that arises regarding surgical prophylaxis with cefazolin* in obese patients undergoing bariatric surgery or cesarean delivery is the initial dose (and also the need for redose). Surgical prophylaxis guidelines suggest a dose of 3 grams for patients weighing at least 120 kg, but supportive data are limited (Am J Health-Syst Pharm 70:195, 2013). More recent PK/PD data including information about target tissue concentrations, although limited, suggest that a 2 gram prophylactic dose is sufficient, with consideration of redosing if the surgical procedure is unexpectedly prolonged. This is supported by a recent retrospective review of 436 surgical patients weighing at least 100 kg in whom the rate of surgical site infection was similar when either a 2 gram or a 3 gram prophylactic dose was administered (Curr Opin Infect Dis 30:180, 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 shortages reported since April
    • [Continue to be in reduced supply]:
      • Aminoglycosides: Amikacin injection, Gentamicin injection, Tobramycin injection
      • Cephalosporins: Cefepime, Cefotetan, Cefotaxime, 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 antimicrobials: Clindamycin injection, Erythromycin lactobionate injection, Mupirocin calcium 2% cream, Mupirocin calcium 2% nasal ointment (unavailable), Vancomycin injection
      • Vaccines: Hepatitis A Virus Vaccine Inactivated, Rabies vaccine (RabAvert), Tetanus and Diphtheria Toxoids Adsorbed, Yellow Fever vaccine
    • [Shortage recently resolved]: Ampicillin injection, Meningococcal vaccines (various)
  • Antimicrobial drugs newly discontinued: No recent discontinuations
  • Other 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/DrugShortage
April 13, 2017

April 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 Treatment Guidelines

  • New evidence-based American Association for Thoracic Surgery (AATS) consensus guidelines for the surgical treatment of infective endocarditis* have been developed. The guidelines focus on surgical treatment and perioperative issues: when to operate, how to prepare the patient for operation, how to operate, and other issues relevant to managing and following patients after surgery (J Thorac Cardiovasc Surg 2017 Jan 24 [Epub ahead of print]).

Updated Drug Approvals for Pediatric Patients

  • The FDA has approved sofosbuvir (Sovaldi)* and ledipasvir/sofosbuvir (Harvoni)* for treatment of hepatitis C virus in children and adolescents:
    • Sofosbuvir in combination with ribavirin is indicated for the treatment of pediatric patients 12 years of age and older or weighing at least 35 kg with genotype 2 or 3 infection without cirrhosis or with mild cirrhosis.
    • Ledipasvir/sofosbuvir is indicated for the treatment of pediatric patients 12 years of age and older or weighing at least 35 kg with genotype 1, 4, 5, or 6 infection without cirrhosis or with mild cirrhosis.

Antimicrobial Stewardship

  • Last month we summarized the recently expanded indications for procalcitonin (PCT). New data add to our understanding of the potential role of PCT in children. In a cohort of 532 prospectively enrolled children with strictly defined, radiographically confirmed community-acquired pneumonia (CAP), PCT concentrations <0.25 ng/mL were strongly associated with a decreased likelihood of detecting typical bacteria and decreased disease severity. PCT concentrations <0.1 ng/mL had a very high negative predictive value, effectively excluding typical bacterial CAP. These findings suggest that PCT may safely be incorporated into treatment algorithms for children with CAP to reduce antibiotic administration and duration (J Pediatric Infect Dis Soc 2017 Feb 3 [Epub ahead of print]).

Emerging Infection Updates

  • Human infections with an Asian lineage avian influenza A (H7N9) virus were first reported in China in March 2013. Since then, annual epidemics of sporadic human infections with Asian H7N9 viruses in China have been reported. During the first four epidemics, about 40% of people with confirmed infection died. China is currently experiencing its fifth epidemic of Asian H7N9 human infection, the largest annual epidemic to date. 460 human infections have been reported since October 1, 2016. The clinical characteristics and risk factors for human infections do not appear to have changed; most infections have been associated with poultry exposure and result in severe respiratory illness. 453 of the infections occurred in mainland China; six are associated with travel to mainland China from Hong Kong (four cases), Macao (one) and Taiwan (one), and one occurred in an asymptomatic poultry worker in Macao. Asian H7N9 viruses have not been detected in people or birds in the United States. Although some limited human-to-human spread continues to be identified, no sustained transmission has been observed. Of concern, ongoing genetic analysis of neuraminidase genes from fifth epidemic viruses indicates that approximately 7-9% of the viruses analyzed to date have known or suspected markers for reduced susceptibility to one or more neuraminidase inhibitors (which are currently recommended for treatment). CDC does not recommend delay or cancellation of trips to China, but travelers are advised to avoid contact with poultry (including poultry markets and farms), birds, and their droppings and to avoid eating undercooked poultry. Infected birds that appear healthy may still be able to transmit the virus to humans. Further information can be found at http://www.who.int/csr/don (MMWR 66:254, 2017).
  • Yellow fever is caused by an arbovirus (Flavivirus) that is transmitted to humans by the bites of infected Aedes and Haemogogus mosquitoes. Since December 2016 there has been an ongoing outbreak of yellow fever in Brazil. The first human cases were reported in the State of Minas Gerais in southeastern Brazil but many epizootic and human cases, mainly in rural areas, are under investigation in neighboring states. These are referred to as sylvatic, or jungle, cases: the virus is transmitted between non-human primates (such as monkeys) via mosquito species found in the forest canopy, and is sporadically transmitted by mosquitoes from non-human primates to human visiting or working in the jungle. As of early April, more than 1500 cases have been reported and yellow fever virus transmission continues to expand towards the Atlantic coast of Brazil in areas not previously deemed to be at risk. At present there is no evidence of human-to-human transmission through Aedes aegypti, the vector that could sustain urban transmission of yellow fever, but the outbreak is affecting areas close to major urban centers where the vaccine is not routinely administered. In response to this outbreak, the list of destinations for which yellow fever vaccination is recommended for travelers has been expanded. Because of the current shortage of yellow fever vaccine, travelers may need to contact a yellow fever vaccine provider well in advance of travel. Detailed information about the situation in Brazil including specific areas considered at risk for yellow fever transmission and vaccine recommendations can be found on at http://www.who.int/csr/don or http://www.cdc.gov/travel (N Engl J Med 2017 Mar 8 [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]: None
    • [Continue to be in reduced supply]:
      • Aminoglycosides: Amikacin injection, Gentamicin injection, Tobramycin injection
      • Cephalosporins: Cefepime, Cefotetan, Cefotaxime (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 antimicrobials: Clindamycin injection, Erythromycin lactobionate injection, Mupirocin calcium 2% cream, Mupirocin calcium 2% nasal ointment (unavailable), Vancomycin injection
      • Vaccines: Hepatitis A Virus Vaccine Inactivated, Rabies vaccine (RabAvert), Tetanus and Diphtheria Toxoids Adsorbed, Yellow Fever vaccine
    • [Shortage recently resolved]: Ampicillin injection, Meningococcal vaccines (various)
  • Antimicrobial drugs newly discontinued: MenHibrix (February 2017)
  • Other discontinuations: 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
March 14, 2017

Sanford Guide releases stewardship solution

Stewardship Assist LogoAs the world’s most trusted source for guidance in the treatment of infectious diseases, The Sanford Guide has been a leader in promoting antimicrobial stewardship, providing clinicians with the tools they need to improve patient outcomes through wise use of antimicrobial agents. While The Sanford Guide has always provided outstanding content with accurate, concise, and reliable recommendations, disseminating locally-focused stewardship information to prescribers in a way that is convenient for them and simple for the stewardship team has presented a challenge for many stewardship programs. With this in mind, The Sanford Guide is pleased to announce the release of Stewardship Assist™, which leverages The Sanford Guide’s popular mobile and web platforms to provide stewardship messaging at the point of care.
 
Designed to allow stewardship teams to update and deploy their antibiograms and recommendations in minutes, Stewardship Assist™ empowers stewardship programs to provide information that is convenient, current, and local. Sanford Guide with Stewardship Assist™ allows Antimicrobial Stewardship Programs to:

  • Display institutional susceptibility/resistance data in a user-friendly antibiogram similar to the Sanford Guide Spectra of Activity.
  • Add localized stewardship recommendations for each organism/antibiotic interaction on the Spectra of Activity.
  • Develop separate antibiograms for different wards and facilities.
  • Display institution-specific stewardship recommendations at the top of Sanford Guide content pages.
  • Disseminate stewardship recommendations through web and mobile app platforms without the need for in-house development or IT support.
  • Reduce costs associated with medical error, inappropriate prescribing, and the need for pharmacy follow-up on targeted cases.

To schedule a demo or learn more about Sanford Guide with Stewardship Assist™, please visit http://www.sanfordguide.com/stewardship.