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The New Hospital-Acquired and Ventilator-Associated Pneumonia Guidelines: A Review of Notable Change

Friday, February 24, 2017   (0 Comments)
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Jordan Gabrielsen, PharmD Candidate 2018
Preceptor: Raymond Lamore, PharmD, BCPS 


The Infectious Disease Society of America (IDSA) recently published the 2016 guidelines for hospital-acquired (HAP) and ventilator-associated pneumonia (VAP), in an effort to provide updated, evidence-based recommendations. These guidelines are based on literature that was evaluated by the IDSA panel as “strong” or “weak” evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Their word choice in making “recommendations” and “suggestions” was based on the strength of the supporting evidence and their clinical experience.1 Certain recommendations made in the new guidelines differ from those made in the 2005 guidelines. The recommendation changes that most pertain to the practice of health-system pharmacists will be summarized and reviewed within this newsletter.  

Recommendation against the use of aminoglycosides

Unlike the 2005 guidelines, which included aminoglycosides as a viable option for pseudomonal coverage, the 2016 guidelines advise against their use for both VAP and HAP.1,2 The guidelines state, “In patients with suspected VAP, we suggest avoiding aminoglycosides if alternative agents with adequate gram-negative activity are available (weak recommendation, low quality evidence)”,1 and “For patients with HAP who are being treated empirically we recommend not using an aminoglycoside as the sole antipseudomonal agent (strong recommendation, very low-quality evidence).”1  

These recommendations were made based on low-quality evidence from the panel’s own meta-analysis of 29 randomized controlled trials (RCTs). They found that the use of aminoglycosides, for the treatment of VAP, was associated with lower clinical response when compared to other antibiotics. It is important to note, that the two studies that significantly influenced these results used pre-set aminoglycoside dosing, and did not monitor drug levels.3,4 The IDSA panel also comments on the poor lung penetration and side effect profile of aminoglycosides, including nephrotoxicity and ototoxicity, to support their recommendation.1 Accounting for the low quality of evidence that supports the aforementioned recommendations, the new guidelines also strongly recommend that local susceptibilities and institutional antibiograms be considered during empiric antibiotic selection.1 When applying these recommendations to clinical practice, pharmacists practicing in the Mid-Atlantic region, should be aware that gram-negative resistance to fluoroquinolones can be up to two-times greater when compared to aminoglycoside resistance.5 Additionally, the adverse effects associated with fluoroquinolones, which have recently been highlighted by the FDA, should not be ignored. These adverse effects can result in permanently damaged tendons, joints, muscles, and nerves.6  

Increased support for the use of Inhaled Antibiotics


Another difference to be aware of is the increasing support for the use of inhaled antibiotics. The 2016 guidelines state, “For patients with VAP due to gram-negative bacilli that are susceptible to only aminoglycosides or polymyxins[…] we suggest both inhaled and systemic antibiotics, rather than systemic antibiotics alone (weak recommendation, very low-quality evidence).”1 This differs from the 2005 guidelines that introduced aerosolized antibiotics as a possible adjunctive therapy in multi-drug resistant (MDR) patients who were not responsive to systemic therapy.2 This suggestion is based on the panel’s meta-analysis of five randomized trials and four observational studies that found the addition of an inhaled antibiotic to systemic therapy increased the resolution of signs and symptoms associated with respiratory infection, while not having any significant effect on nephrotoxicity or mortality.1 Two additional studies evaluated pneumonia caused by gram-negative organisms found inhaled colistin reduced the duration of mechanical ventilation.1,7,8 Other studies, although not specific to pneumonia, found that inhaled antibiotics decreased the need for IV antibiotics, and that their use did not result in increased antibiotic resistance.1,9,10  Overall, considering the lack of treatment options there are for patients with pneumonia caused by MDR gram-negative organisms, inhaled antibiotics may be reasonable as a “last line” adjunctive therapy, while efforts continue in developing novel systemic antibiotic therapies.11   

Limited Length of therapy

Arguably the most notable change in the 2016 guidelines is the recommendation to limit the length of antibiotic therapy to 7 days, in both VAP and HAP.  This "strong" recommendation was made based on moderate-quality evidence (VAP) and low-quality evidence (HAP). This differs from the 2005 guidelines which only recommended a shortened duration of therapy (7 day therapy) for HAP, VAP, and HCAP that were not due to Pseudomonas aeruginosa.2 The evidence included two systematic reviews of RCT studies12,13 and an observational study14 comparing short courses of VAP treatment (3-7 days) to longer courses (9-15 days); it was found that shorter antibiotic courses reduced patient antibiotic exposure and decreased recurrence of VAP due to MDR organisms while also having no effect on mortality, hospital length of stay, VAP recurrence, treatment failures and duration of mechanical ventilation. When applying this recommendation to clinical practice, it is always important to verify the patient's clinical progression.   

Conclusion


Pharmacists continue to play an important role in assisting with the treatment of HAP and VAP.  The 2016 IDSA Guidelines will surely support our efforts in recommending appropriate antibiotics (using knowledge of guidelines and local antibiogram data), monitoring for patient response and drug related side effects, and helping to minimize the duration of antibiotic therapy. Although this newsletter reviews three of the recommendations/suggestions that are most significant to health-system pharmacists, there are many others within the guidelines that impact patient care. 1,2 Therefore, a complete review is always recommended. 
 
References: 
 
(1) Kalil AC, Metersky ML, Klompas M, et al. Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Pract ice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. IDSA. July 2016. doi: 10.1093/cid/ciw353 
 
(2) Guidelines for the Management of Adults with Hospital-acquired, Ventilator-associated, and Healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005; 171:388-416. doi: 10.1164/rccm.200405-644ST 
 
(3) Alvarez LF, On behalf of The Serious Infection Study Group. Efficacy of Meropenem as Monotherapy in the Treatment of Ventilator-Associated Pneumonia. J of Chemotherapy. 2013; 13: 17-18. 
 
(4) Sieger B, Berman SJ, Geckler RW, Farkas, SA. Empiric treatment of hospital-acquired lower respiratory tract infections with meropenem or ceftazidime with tobramycin: a randomized study. Meropenem Lower Respiratory Infection Group. Crit Care Med. 1997; 25:1663-70. 
 
(5) Resistance Map. The Center for Disease Dynamics, Economics & Policy Website. https://resistancemap.cddep.org/CountryPageSub.php?countryId=38&country=United+States. Accessed November 28, 2016.  
 
(6) FDA updates warnings for fluoroquinolone antibiotics. U.S. Food and Drug Administration website. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm513183.htm Published July 26, 2016. Accessed November 28, 2016. 
 
(7) Doshi NM, Cook CH, Mount KL, et al. Adjunctive aerosolized colistin for multidrug resistant gram-negative pneumonia in the critically ill: a retrospective study. BMC Anesthesiol. 2013; 13:45. 

(8) Tumbarello M, De Pascale G, Trecarichi EM, et al. Effect of aerosolized colistin as adjunctive treatment on the outcomes of microbiologically documented ventilator-associated pneumonia caused by colistin-only susceptible gram-negative bacteria. Chest.  2013; 144:1768-75. 
 
(9) Palmer LB, Smaldone GC. Reduction of bacterial resistance with inhaled antibiotics in the intensive care unit. Am J Respir Crit Care Med. 2014; 189: 1225-33.  
 
(10) Nseir S, Di Pompeo C, Pronnier P, et al. Nosocomial tracheobronchitis in mechanically ventilated patients: incidence, aetiology and outcome. Eur Respir J. 2002; 20:1483-9.  
 
(11) Antibiotics NCE pipeline. BioCentry Website. http://www.biocentury.com/antibioticsncepipeline.htm. 2012. Accessed November 28, 2016. 
 
(12) Pugh R, Gran C, Cooke RP, Dempsey g. Short-course versus prolonged-course antibiotic therapy for hospital- acquired pneumonia in critically ill adults. Cochrane Database Syst Rev. 2015; 8: Cd007577. 
 
(13) Dimopoulos G, Poulakou G, Pneumatikos IA, et al. Short- vs long-duration antibiotic regimens for ventilator- associate pneumonia: a systematic review and meta-analysis. Chest. 2013; 144: 1759-67. 
 
(14) Hedrick TL, McElearney ST, Smith RL, et al. Duration of antibiotic therapy for ventilator-associated pneumonia caused by non-fermentative gram-negative bacilli. Surg Infect. 2007; 8:589-97. 


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