Changes in Therapy Guideline for Nosocomial Pneumonia

Contagion, May 2017, Volume 2, Issue 2

Strategic Alliance Partners | <b>Society of Infectious Diseases Pharmacists</b>

Contagion® Editorial Advisory Board member, Khalid Eljaaly, PharmD, BCPS, CAPP, discusses key updates in the Infectious Diseases Society of America and the American Thoracic Society recommendations.

The Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) recently published a joint update to their nosocomial pneumonia guideline.

1,2

About 11 years have passed since the first guideline was published, and so identifying key changes between the new guideline and the original might be difficult for some end users. In this article, I highlighted several key differences and updates related to antibiotic therapy.

First, the previous guideline included healthcare-associated pneumonia (HCAP) in the spectrum of hospital-acquired pneumonia (HAP) and ventilator-acquired pneumonia (VAP). This was done because patients with HCAP were thought to be at high risk for multidrug-resistant (MDR) pathogens due to exposure to pathogens within healthcare facilities. In the new guideline, HCAP is included under the guideline for community-acquired pneumonia because recent data

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showed that many patients are not at high risk for MDR organisms as previously thought and therefore should not be treated in the same manner as patients with HAP or VAP.

Second, additional risk factors for MDR pathogens are provided in the new guideline. These risk factors include the septic shock at time of VAP and acute respiratory distress syndrome or acute renal replacement therapy preceding VAP. All risk factors for HCAP have been removed.

Third, the previous guideline recommended the use of 2 empiric antipseudomonal agents for all patients at high risk for MDR pathogens. In contrast, the new guideline recommended two agents for patients with structural lung disease that increases the risk of gram-negative infection (ie, bronchiectasis or cystic fibrosis). In addition, the older guideline suggested considering two empiric antipseudomonal agents in patients with VAP with a risk factor for MDR pathogens, those in units where more than 10% of gram-negative isolates are resistant to an agent being considered for monotherapy, and those in an ICU where local antimicrobial susceptibility rates are not available. The authors believed that this would reduce patient harm, unnecessary exposure to broad-spectrum antibiotic coverage, and microbial resistance development. The guideline further recommends having a specific antibiogram for intensive care patients.

Fourth, the new guideline clearly recommends including empiric coverage for methicillin-susceptible Staphylococcus aureus (MSSA) for VAP patients if coverage for methicillin-resistant S. aureus was not indicated. The antibiotics suggested for these infections include piperacillin-tazobactam, cefepime, levofloxacin, imipenem, or meropenem.

Fifth, the new guideline recommends several therapeutic options and removes other options. For example, the new guideline does not include some antibiotics that were mentioned in the previous guideline as a possible option for empiric therapy, such as ampicillin/sulbactam, ceftriaxone, moxifloxacin, and ertapenem. This is because these agents do not have antipseudomonal activity, while all of the options included in the new guideline have activity against Pseudomonas aeruginosa. In addition, the combination of both inhaled and systemic antibiotics is now recommended for patients with VAP because of gram-negative bacilli that are susceptible to only aminoglycosides or polymyxins.

Whereas the previous guideline did not discuss tigecycline and doripenem, the new guideline states that these medications were associated with worse outcomes in patients with VAP. Aminoglycosides were only recommended as adjunctive agents, not as the sole empiric antipseudomonal antibiotic, for patients with HAP. Interestingly, the new guideline states that it is acceptable to use aztreonam as an adjunctive antibiotic with another beta-lactam—based antibiotic in the absence of other options because of having different targets in the bacterial cell wall.

Sixth, the new guideline makes some changes regarding antibiotic dosing. Although the previous guideline did not provide a recommended dose for any polymyxin, the new guideline recommends dosing colistin as a 5-mg/kg IV as a loading dose, followed by a maintenance dose of a 2.5-mg

×

(1.5

×

creatinine clearance + 30) IV every 12 hours, whereas it recommends dosing polymyxin B as 2.5 to 3 mg/kg/day divided in 2 daily IV doses. The cefepime and aminoglycosides doses were modified as following: the cefepime IV dose was changed from 1 to 2 g every 8 to 12 hours to 2 g every 8 hours; gentamicin and tobramycin IV doses were changed from 7 mg/kg/day to 5 to 7 mg/kg/day; and the amikacin IV dose was changed from 20 mg/kg/day to 15 to 20 mg/kg/day. Moreover, the new guideline recommends considering a loading dose of vancomycin for severe infections and extended IV infusion for piperacillin/tazobactam, cefepime, ceftazidime, imipenem, and meropenem, as well as basing antibiotic dosing on the pharmacokinetic/pharmacodynamic properties data rather than the manufacturer’s prescribing information.

Finally, the new guideline discusses the use of biomarkers to treat VAP and HAP. Procalcitonin, soluble triggering receptor expressed on myeloid cells, and C-reactive proteins were not recommended to be used to decide whether to initiate antibiotic therapy; however, procalcitonin was suggested in addition to clinical criteria to guide the antibiotic therapy discontinuation as it was associated with decreased antibiotic exposure without increasing adverse outcomes.

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In conclusion, the new guideline for HAP and VAP no longer includes HCAP. One antipseudomonal agent is currently recommended for most HAP and VAP cases unless patients have high risk for MDR pathogens, while MSSA coverage is needed in patients with VAP. Various changes and additions were made to antibiotic choice, dose, route of administration, and duration of therapy. A summary of the changes is included in the Table.

Table: Updates to IDSA/ATS Guideline for Nosocomial Pneumonia Snapshot

Current Guideline

Previous Guideline

HCAP will be included with CAP

HCAP was included in the spectrum of HAP/VAP

Suggest 2 empiric antipseudomonal agents only for selected patients

Recommend 2 empiric antipseudomonal agents for all

patients at high risk for MDR bacteria

Recommend empiric coverage of MSSA in VAP

No empiric coverage of MSSA in VAP

All patients need empiric antipseudomonal agent

Agents without antipseudomonal activity are acceptable

in some cases

Suggest procalcitonin plus clinical criteria to guide antibiotic discontinuation

No statement

Dosing of polymyxins was added

Not mentioned

Cefepime IV: 2 g every 8 hours

Cefepime IV: 1-2 g every 8-12 hours

Gentamicin and tobramycin IV: 5-7 mg/kg/day

Gentamicin and tobramycin IV: 7 mg/kg/day

Amikacin IV: 15-20 mg/kg/day

Amikacin IV: 20 mg/kg/day

HCAP indicates healthcare-associated pneumonia; CAP, community-acquired pneumonia; VAP, ventilator-acquired pneumonia;

HAP, hospital-acquired pneumonia; MDR, multidrug resistant; MSSA, methicillin-susceptible Staphylococcus aureus.

Dr. Eljaaly, PharmD, BCPS, is a postdoctoral pharmacy fellow in infectious diseases/antibiotic stewardship in the College of Pharmacy at the University of Arizona in Tucson, Arizona. He is a member of the stewardship committee in the SIDP and a member of Social Media Committee in both the SIDP and Infectious Diseases Practice and Research Network of the American College of Clinical Pharmacy.

References:

  1. Kalil AC, Metersky ML, Klompas M, et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. 2016;63(5):e61-e111. doi: 10.1093/cid/ciw353.
  2. American Thoracic Society; Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005;171(4):388-416.
  3. Chalmers JD, Rother C, Salih W, Ewig S. Healthcare-associated pneumonia does not accurately identify potentially resistant pathogens: a systematic review and meta-analysis. Clin Infect Dis. 2014;58(3):330-339. doi: 10.1093/cid/cit734.
  4. Gross AE, Van Schooneveld TC, Olsen KM, et al. Epidemiology and predictors of multidrug-resistant community-acquired and health care-associated pneumonia. Antimicrob Agents Chemother. 2014;58(9):5262-5268. doi: 10.1128/AAC.02582-14.
  5. Yap V, Datta D, Metersky ML. Is the present definition of health care-associated pneumonia the best way to define risk of infection with antibiotic-resistant pathogens? Infect Dis Clin North Am. 2013;27(1):1-18. doi: 10.1016/j.idc.2012.11.002.
  6. Jones BE, Jones MM, Huttner B, et al. Trends in antibiotic use and nosocomial pathogens in hospitalized veterans with pneumonia at 128 medical centers, 2006-2010. Clin Infect Dis. 2015;61(9):1403-1410. doi: 10.1093/cid/civ629.
  7. Valles J, Martin-Loeches I, Torres A, et al. Epidemiology, antibiotic therapy and clinical outcomes of healthcare-associated pneumonia in critically ill patients: a Spanish cohort study. Intensive Care Med. 2014;40(4):572-581. doi: 10.1007/s00134-014-3239-2.
  8. Schuetz P, Briel M, Christ-Crain M, et al. Procalcitonin to guide initiation and duration of antibiotic treatment in acute respiratory infections: an individual patient data meta-analysis. Clin Infect Dis. 2012;55(5):651-662. doi: 10.1093/cid/cis464.
  9. Schuetz P, Müller B, Christ-Crain M, et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev. 2012;(9):CD007498. doi: 10.1002/14651858.CD007498.pub2.