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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.

March 13, 2017

March ID Update

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New Treatment Guidelines

  • New IDSA clinical practice guidelines for the evaluation, diagnosis, and management of healthcare-associated ventriculitis and meningitis have been published (Clin Infect Dis 64:e34, 2017). The guidelines are available for download on the IDSA website.

Antimicrobial Stewardship

  • In late February the FDA expanded the indications for the biomarker procalcitonin (PCT) to include these uses:
    • As a marker of potential microbial invasion and progression to severe sepsis or septic shock in critically ill patients.
    • As an aid in determining the need for antibacterial therapy in patients with acute exacerbation of COPD and community-acquired pneumonia. The likelihood of invasive bacterial infection with a normal PCT level (≤0.25 ng/mL) is less than 5%. PCT levels do not increase unless colonizing bacteria like pneumoniae, H. influenzae, and M. catarrhalis are invading as opposed to colonizing the airway.
    • As an aid in determining the length of antibiotic therapy in both bacteria-induced sepsis/septic shock and community-acquired pneumonia.
    • Note that the FDA did not address the helpful role of PCT levels in hypotensive patients with possible septic shock. A normal PCT level excludes bacteremia as a cause in 95% of the patients. In short, PCT levels are useful in antibiotic stewardship programs. The combination of serum PCT levels and pathogen detection (virus and bacteria) with multiplex PCR platforms can eliminate uncertainty and thereby allow customization of antibacterial and/or antiviral therapy.

Practice Pearls

  • Currently there are colistin (polymyxin E)* dosing recommendations from three sources: 1) an international pharmacokinetics (PK) study group, using creatinine clearance (CrCl)-based dosing, 2) the European Medicines Agency (EMA), also CrCl-based (with broader divisions than the PK study group), and 3) the US FDA, which uses weight- and CrCl-based dosing as found in the official prescribing information. The Sanford Guide editors favor the approach of the PK study group as published  (Clin Infect Dis 2016 Dec 23 [Epub ahead of print]).
     
    In 2011 the PK study group published complex colistin dosing recommendations derived from an interim analysis of 105 critically ill patients (Antimicrob Agents Chemother 55:3284, 2011). The group has now updated these recommendations based on their final analysis of data from 214 patients. The result is a more clinician-friendly dosing approach designed to achieve an average steady-state colistin plasma concentration of 2 μg/mL. Patients are administered a loading dose (expressed as mg of colistin base activity) of 4 x body weight (using the lower of actual or ideal body weight) followed by a maintenance regimen beginning 12 hours later using a “look-up” table of daily dose based on CrCl (divided in 10 mL/min increments). The maintenance dose should be administered in two divided doses 12 hours apart. The group also provides dosing recommendations for patients receiving intermittent hemodialysis, SLED, and CRRT. Full details are provided on our colistin* page. Colistin dosing remains a challenge. We recommend use of polymyxin B rather than colistin with one importance exception: polymyxin B does not achieve adequate urine concentrations. Hence, colistin is required to treat multidrug-resistant gram-negative infections of the urinary tract.
  •  

  • Eosinophilic pneumonia is a rare disease characterized by the accumulation of eosinophils in the lung. It may occur following exposure to certain drugs (especially antibiotics and NSAIDs), toxins, or radiation. Eosinophilic pneumonia is characterized by fever, diffuse bilateral pulmonary infiltrates, hypoxemia, and bronchoalveolar lavage with >25% eosinophils. Eosinophil production and migration into the lung is facilitated by release of interleukin 5 from T-helper 2 lymphocytes as well as eotaxin secretion from activated alveolar macrophages (Clin Infect Dis 50:e63, 2010). A recent systematic literature review identified 35 cases of presumed daptomycin-induced eosinophilic pneumonia. 83% of the patients were male, and mean age was 65.4 years. Clinical findings included dyspnea (94%), infiltrates/opacities on CT or chest X-ray (86%), peripheral eosinophilia (77%), and fever (57%). Daptomycin dose ranged from 4 to 10 mg/kg/day (adjusted for renal function). Mean duration of therapy before symptom onset was 2.8 weeks. Symptoms improved one to seven days after discontinuation of daptomycin; 66% of the patients were also prescribed corticosteroids. The mechanism of daptomycin-induced eosinophilic pneumonia is not known but may involve an inflammatory response triggered by binding of daptomycin to lung surfactant with subsequent accumulation in the alveolar space (Antimicrob Resist Infect Control 2016 Dec 12 [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]: Rabies vaccine (RabAvert)
    • [Continue to be in reduced supply]
      • Aminoglycosides: Amikacin, 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 injection, 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, Meningococcal vaccines (various), Tetanus and Diphtheria Toxoids Adsorbed, Yellow Fever vaccine
    • [Shortage recently resolved]: None
  •  

  • Antimicrobial drugs recently discontinued: 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
February 15, 2017

February ID Update

The 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. To receive monthly ID Updates by e-mail, subscribe now. We will not share your e-mail address, and you may unsubscribe at any time.
 

FEBRUARY 2017

Updated Treatment Guidelines

  • Updated guidelines for the treatment of Helicobacter pylori infection from the American College of Gastroenterology have been published (Am J Gastroenterol 112:212, 2017). The guidelines are available for download on the ACG website.

Practice Pearls

  • Carbapenem* antibiotics are known to rapidly decrease valproic acid (VPA) concentrations. Doripenem, ertapenem, imipenem, meropenem, and panipenem have all been implicated, but the precise mechanism of the interaction is not fully understood. The most important metabolite of VPA is the inactive glucuronide, and it has been suggested that the key step is inhibition by carbapenems of acylpeptide hydrolase, an enzyme that hydrolyzes VPA-glucuronide (VPA-G) back to the parent compound (resulting in enhanced VPA-G urinary excretion). Other possible mechanisms include carbapenem-induced inhibition of intestinal VPA absorption, increased synthesis of VPA-G, and inhibition of VPA efflux from erythrocytes. In a retrospective study, VPA concentrations were reduced approximately 60% within 24 hours; the magnitude of decrease in VPA concentration was higher with ertapenem and meropenem than with imipenem (Ther Drug Monit 38:587, 2016).
     
    The interaction between meropenem and VPA was further examined on a large scale using a retrospective analysis of VPA therapeutic drug monitoring records from neurosurgery inpatients at a hospital in China. 381 records from 301 patients treated with VPA with or without meropenem over a three-year period were collected. Two findings extend our knowledge of this interaction: 1) the occurrence of the interaction is independent of the daily dose of VPA and meropenem, suggesting that the decrease in VPA concentration cannot be reversed by simply increasing the VPA dose, and 2) discontinuation of meropenem for more than seven days is necessary for recovery of the VPA concentration (J Clin Pharm Ther 2017 Feb 1 [Epub ahead of print]).
  •  

  • Clindamycin* is a lipophilic drug that may require dosage adjustment in obese patients, yet we have little to no pharmacokinetic or outcomes data in obesity (adult or pediatric) to guide us. Data from three separate prospective trials were recently combined to perform a clindamycin population pharmacokinetic analysis in 220 children, 76 of whom had a BMI ≥95th percentile for age. Total body weight was found to be the most appropriate weight for dosing in obese and non-obese children. Alternative measures of body composition (normal fat mass, fat free mass, and lean body weight) resulted in inferior model performance. Study limitations acknowledged by the authors include the use of multiple study designs and populations possibly introducing variability into the model, missing laboratory data for many study subjects, and possible misclassification of obesity status for some subjects (Antimicrob Agents Chemother 2017 Jan 30 [Epub ahead of print]).
  • In 2008, the U.S. Food and Drug Administration (FDA) notified fluoroquinolone manufacturers that a boxed warning in the product labeling concerning the increased risk of tendinitis and tendon rupture was necessary. Last year, the FDA announced it was requiring a stronger black box warning for all fluoroquinolones, advising that the serious side effects associated with fluoroquinolones generally outweigh the benefits for patients with acute sinusitis, acute bronchitis, and uncomplicated UTI who have other treatment options. The side effects can involve the tendons, muscles, joints, nerves, and CNS. For patients with the aforementioned diseases, fluoroquinolones should be reserved for those who do not have alternative treatment options. The need for an upgraded warning was fueled in part by recent studies such as a nested, case-control analysis from the Taiwan National Health Insurance Research Database in which fluoroquinolone usage was associated with an approximately 2-fold increase in risk of aortic aneurysm and dissection within 60 days of exposure (JAMA Intern Med 175:1839, 2015).
     
    In light of this, a reader inquired as to whether the first-line status of fluoroquinolones for CAP in certain patient subgroups might be downgraded. In our response, we pointed out that the warning pertains to the use of fluoroquinolones for relatively minor infections, of which two (sinusitis and bronchitis) are often self-limited, viral in etiology, and for which the benefit of any antibiotic is marginal. Bacterial pneumonia is another matter, and for now a change in our recommendations is not anticipated. IDSA has a guidelines committee working on CAP recommendations and it will be interesting to see what comes from that. In addition, emerging data suggest that current treatment recommendations are based on a distorted perception of the cause of CAP (N Engl J Med 373:415, 2015; Clin Infect Dis 62:817, 2016). For now, the benefit of an antibiotic in CAP is well established and the use of a fluoroquinolone as a first-line agent in the older, more medically complicated adult remains reasonable.
  •  

  • Metronidazole*, in clinical use for over 50 years, has an important role in the treatment of trichomoniasis, giardiasis, amebiasis, bacterial vaginosis, H. pylori, and various anaerobic bacterial infections. Why does metronidazole lack activity against aerobic bacteria?
     
    Metronidazole enters the bacterial cell via passive diffusion. It is then reduced in the cytoplasm to a short-lived nitroso free radical intermediate that binds nonspecifically to bacterial DNA. This results in inhibition of DNA synthesis and strand breakage, killing the cell. Aerobic bacterial cells lack electron-transfer proteins with sufficient negative redox potential to donate the necessary electrons to metronidazole. In anaerobes, there are electron-transfer proteins like flavodoxin and ferredoxin that have a redox potential lower than metronidazole, so they will give their electrons up and reduce the drug. Redox potential describes the tendency of a chemical species to accept or donate electrons from/to another species; positive potential is the tendency to accept electrons, negative potential is the tendency to donate electrons.
     
    Resistance to metronidazole among Bacteroides group species is rare, although a few case reports of multidrug-resistant B. fragilis have recently appeared (MMWR 62:694, 2013). However, there are at least two anaerobes in which metronidazole resistance is common. One is Propionibacterium acnesP. acnes is typically highly susceptible to clindamycin but resistant to metronidazole, which explains the superiority of topical clindamycin for mild-to-moderate acne. Topical metronidazole is useful for acne rosacea, however, presumably due to its antiinflammatory properties (Curr Med Res Opin 15:298, 1999).
     
    The other one is Clostridium tertiumC. tertium distinguishes itself among other members of the Clostridium genus as a non-toxin-producing, aerotolerant species. C. tertium is rarely associated with bacteremia. Patients are typically (but not always) neutropenic with injury to the gastrointestinal mucosa, and they frequently have a history of exposure to beta-lactam antibiotics (especially third-generation cephalosporins). C. tertium is commonly (but not always) resistant to clindamycin as well (Clin Infect Dis 32:975, 2001).

Drug Shortages (US)

  •  Antimicrobial drugs or vaccines in reduced supply 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]: Amikacin, Amoxicillin/clavulanate 1000 mg/62.5 mg ER tablets, Ampicillin injection, Ampicillin/sulbactam, Cefepime, Cefotetan, Cefoxitin, Ceftazidime, Ceftriaxone, Cefuroxime injection, Ciprofloxacin oral suspension, Clindamycin injection, Erythromycin lactobionate injection, Gentamicin injection, Hepatitis A Virus Vaccine Inactivated, Meningococcal vaccines (various), Mupirocin calcium 2% cream, Ofloxacin 0.3% ophthalmic solution, 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), Piperacillin/tazobactam, Tetanus and Diphtheria Toxoids Adsorbed, Tobramycin injection, Vancomycin injection, Yellow Fever vaccine
    • [Shortage recently resolved]: Tigecycline
  •  

  • Antimicrobial drugs currently unavailable due to manufacturing delays or product discontinuation:
    • [New on the list]: None
    • [Continue to be unavailable]: Cefotaxime injection, Mupirocin calcium 2% nasal ointment, Penicillin G procaine injection
  •  

  • Antimicrobial drugs discontinued: 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