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)