Klompas, Michael

Clinical Infectious Diseases

Harvard University - DASH 

 Editorial Commentary: Evidence vs Instinct for PneumoniaPrevention in Hospitalized Patients  (Article begins on next page)The Harvard community has made this article openly available.Please share how this access benefits you. Your story matters.Citation Klompas, Michael. 2014. “Editorial Commentary: Evidence vsInstinct for Pneumonia Prevention in Hospitalized Patients.”Clinical Infectious Diseases: An Official Publication of theInfectious Diseases Society of America 60 (1): 76-78.doi:10.1093/cid/ciu744. http://dx.doi.org/10.1093/cid/ciu744.Published Version doi:10.1093/cid/ciu744Accessed February 17, 2015 8:46:08 AM ESTCitable Link http://nrs.harvard.edu/urn-3:HUL.InstRepos:13581195Terms of Use This article was downloaded from Harvard University's DASHrepository, and is made available under the terms and conditionsapplicable to Other Posted Material, as set forth athttp://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAAEDITORIAL COMMENTARYEvidence vs Instinct for Pneumonia Preventionin Hospitalized PatientsMichael Klompas1,21Departmentof Population Medicine, HarvardMedicalSchoolandHarvardPilgrim HealthCare Institute,and2Department of Medicine,BrighamandWomen’s Hospital,Boston,Massachusetts(See the Major Article by Roquilly et al on pages 64–75.)Keywords. hospital-acquired pneumonia; quality improvement; prevention, surveillance; ventilator-associated pneumonia.Over the years, literally dozens of inter-ventions have been proposed to preventhospital-acquired pneumonia. Most hos-pitals have combined a subset of thesepractices into “ventilator bundles” thatare mandatory for all mechanically venti-lated patients and sometimes all criticallyill patients. Typical bundle elements in-clude elevation of the head of the bed,routine oral carewith chlorhexidine, dailysedative interruptions, daily assessmentof readiness to extubate, deep venousthrombosis prophylaxis, and stress ulcerprophylaxis. Bundles vary broadly, how-ever, from hospital to hospital [1].Despite the popularity and broad pen-etration of ventilator bundles, the evi-dencesupportingeachbundlecomponentis highly variable. Some components,such as routine sedative interruptionsand daily assessments of readiness to ex-tubate, have been well studied and consis-tently associated with better outcomes[2–5]. Other components, such as head-of-bed elevation, have only been assessedin few patients [6, 7]. Finally, there aremany successful interventions to preventpneumonia that are not part of most hos-pitals’ bundles [8].A systematic review and meta-analysisin this issue of Clinical Infectious Diseaseshelpfully summarizes some of the vast lit-erature on preventing hospital-acquiredpneumonia and provides some clarityabout the relative value of different inter-ventions. Roquilly and colleagues identi-ﬁed 157 randomized controlled trialsevaluating more than 20 different inter-ventions. They conducted a series ofmeta-analyses to determine the impactof each intervention. The investigators se-lected hospital mortality as their primaryoutcome rather than hospital-acquiredpneumonia. Of the 20 interventions stud-ied, the only measure associated with adecreaseinhospitalmortalitywasselectivedigestive decontamination with regimensthat included systemic antimicrobials(relative risk, 0.78, 95% conﬁdence inter-val, .69–.89). Patient positioning, subglotticsecretion drainage, closed suctioning sys-tems, probiotics, early tracheotomy, earlyenteral feeding, stress ulcer prophylaxis,silver-coated endotracheal tubes, oral de-contamination with antiseptics or antibiot-ics, selective digestive decontaminationwithout systemic antimicrobial therapy,and all the other interventions studiedhad no impact on mortality.These provocative ﬁndings are a shotover the bow of infection prevention andquality improvement programs. Thismeta-analysis simultaneously challengesthe validity of current ventilator bundlesand begsthe question whyselective diges-tive decontamination with systemic anti-microbials is not routinely employed?In truth, evidence has been gatheringfor years that the classic ventilator bundlem e r i t sr e v i s i o n .S o m eb u n d l ec o m p o -nents, such as stress ulcer prophylaxis,paradoxically increase pneumonia risk[9]. Other bundle components, such asroutine oral care with chlorhexidine, donot clearly prevent ventilator-associatedpneumonia and may even increase mor-tality risk [10, 11].A major challenge in pneumonia pre-vention science is the subjectivity andpoor speciﬁcity of clinical criteria to de-ﬁne pneumonia [12, 13]. Subjectivityallows for the possibility that lower pneu-monia rates in the treatment arms ofopen-label studies are due to observerbias. Poor speciﬁcity allows for the possi-bility that some of the decreases in pneu-monia rates in both open-label andReceived 8 September 2014; accepted 11 September 2014;electronically published 24 September 2014.Correspondence: Michael Klompas, MD, MPH, Departmentof Population Medicine, Harvard Medical School and HarvardPilgrim Health Care Institute, 133 Brookline Ave, 6th Fl, Boston,MA 02215 (mklompas@partners.org).Clinical Infectious Diseases® 2015;60(1):76–8© The Author 2014. Published by Oxford University Press onbehalf of the Infectious Diseases Society of America. This isan Open Access article distributed under the terms of theCreative Commons Attribution-NonCommercial-NoDerivslicence (http://creativecommons.org/licenses/by-nc-nd/4.0/),which permits non-commercial reproduction and distribution ofthework,inanymedium,providedtheoriginalworkisnotalteredor transformedin anyway,and thatthework properly cited. Forcommercial re-use, please contact journals.permissions@oup.com.DOI: 10.1093/cid/ciu74476 ￿ CID 2015:60 (1 January) ￿ EDITORIAL COMMENTARYdouble-blind studies are due to less colo-nization rather than less pneumonia [14].These challenges are the reasons whyRoquilly and colleagues selected mortalityas their primary outcome rather thanhospital-acquired pneumonia. Other work-ers have reached similar conclusions [14–16]. Indeed, the Society of HealthcareEpidemiologists of America and Infec-tious Disease Society of America’sl a t e s trevision of their compendium of strategiesto prevent ventilator-associated pneumo-nia speciﬁcally prioritizes interventions as-sociated with less time to extubation,shorter intensive care stays, lower hospitalmortality, less antibiotic prescribing, and/or lowercosts over interventions associatedwith lower ventilator-associated pneumo-nia rates alone [17]. The compendiumrecommends using noninvasive mechani-cal ventilation whenever possible, mini-mizing sedation, interrupting sedativesand assessing readiness to extubate daily,mobilizing patients early, using endotra-cheal tubes with subglottic secretiondrainage, changing ventilator circuitsonly if visibly soiled or malfunctioning,and elevating the head of the bed.Thisbundleofrecommendationsisdif-ferent and more extensive than those sug-gested by the meta-analysis by Roquillyand colleagues. There are 2 reasons forthis. First, the compendium authors eval-uated some interventions that were notconsidered by Roquilly and colleaguessuch as noninvasive positive pressureventilation, minimizing sedation, dailysedative interruptions, and daily assess-ment of readiness to extubate. Second,the compendium authors found meritin interventions associated with lesstime to extubation, shorter lengths-of-stay, less antibiotic prescribing, and/orlowercosts in addition to those associatedwith lower mortality rates. This is impor-tant, partly because these are additionalclinically meaningful outcomes, andpartly because the amount of evidencesupporting different interventions variesconsiderably. Some interventions, suchas oral and digestive decontamination,have been studied in literally tens of thou-sands of patients whereas other inter-ventions, such as elevating the head ofthe bed, have only been studied in a fewhundred patients. Most small studieslack adequate power to detect changesin mortality rates but can sometimesshow positive effects on other outcomes.Most strikingly, however, despiteacknowledging that selective digestivedecontamination is one of the only pneu-monia prevention practice associatedwith lower mortality rates, the compendi-um authors downgraded this measure toa “special practice.” Special practices arerecommended only for units with persis-tently high ventilator-associated pneumo-nia rates despite high rates of adherenceto the strategies suggested above. In doingso, the compendium authors echoed theconcerns of many North American practi-tionerswhofearthatwidespreaduseofan-tibiotics for digestive decontamination willultimately increase antibiotic resistanceand Clostridium difﬁcile infections, partic-ularly in North American hospitals wheredrug resistance is more prevalent than inNorthern Europe. These practitioners fearthatthe deleterious consequences of multi-drug resistance will ultimately outweighany short-term mortality gain associatedwith digestive decontamination.And indeed, resistome analyses of thegut ﬂora of individual patients assignedto digestive decontamination do revealprogressive selection for antimicrobial re-sistance [18, 19]. At the population level,however, the data on resistance are moreambiguous. A recent meta-analysis of35 studies found no difference betweendecontamination patients and controlpatients in the frequency of colonizationor infection with methicillin-resistantStaphylococcus aureus, vancomycin-resistant enterococci, aminoglycoside-resistant Gram-negative bacilli, or ﬂuoro-quinolone-resistant Gram-negative bacilli[20]. Remarkably, decontamination wasassociated with less Gram-negative bacilliresistant to third-generation cephalospo-rins or polymyxins.These ﬁndings ﬂy in the face of ecolog-ical studies associating greater antibioticprescribing with greater rates of antibioticresistance [21, 22]. Multiple explanationshave been proposed [20]. Some suggestthat lowering infection rates overall maydecrease the absolute incidence of drug-resistant infections even if the proportionofdrug-resistantpathogensmaybehigher.Others have noted that in many studies(but not all) patients randomized to de-contamination ended up receiving fewerantibiotics in total compared to controlpatients perhaps because therewere fewernew infections to treat.A recurring critique of the decontami-nation literature is that most studies onlyfollowed a limited number of patients fora limited period of time. Observationaldata are now accruing, however, that themortality beneﬁt of digestive decontami-nation may be sustained and that lowrates of antibiotic resistance can persistfor years [23, 24].As an infectious disease physician, I aminstinctively uncomfortable with digestivedecontamination with systemic antimicro-bials. I focus muchof my clinical work andteaching on encouraging clinicians to useantimicrobials as judiciously as possible.Nonetheless,wecannotignoretheaccumu-lating evidence on digestive decontamina-tion. There are precious few interventionsin critical care associated with a 22% mor-tality reduction. And we must admit thatthere are other areas of infectious diseasepractice where we’ve come to accept rou-tine antimicrobial prophylaxis (eg, bonemarrow transplants, surgical prophylaxis,human immunodeﬁciency virus with lowCD4counts).Itbehoovesusnowtoconductthe deﬁnitive studies of digestive decon-tamination in North America with long-enough follow-up periods to settle thequestion for once and for all of the relativebeneﬁts and risks of routine digestive de-contamination. We owe it to our patients.NotePotential conﬂict of interest. Authorcertiﬁesno potential conﬂicts of interest.EDITORIAL COMMENTARY ￿ CID 2015:60 (1 January) ￿ 77The author has submitted the ICMJE Formfor Disclosure of Potential Conﬂicts of Interest.Conﬂicts that the editors consider relevant to thecontent of the manuscript have been disclosed.References1. Klompas M. Ventilator-associated pneumo-nia: is zero possible? Clin Infect Dis 2010;51:1123–6.2. Esteban A, Frutos F, Tobin MJ, et al. A com-parison of four methods of weaning patientsfrom mechanical ventilation. Spanish LungFailure Collaborative Group. N Engl J Med1995; 332:345–50.3. Girard TD, Kress JP, Fuchs BD, et al. Efﬁcacyand safety of a paired sedation and ventilatorweaning protocol for mechanically ventilatedpatients in intensive care (Awakening andBreathing Controlled trial): a randomisedcontrolled trial. Lancet 2008; 371:126–34.4. Ely EW, Baker AM, Dunagan DP, et al. Effecton the duration of mechanical ventilation ofidentifyingpatientscapableofbreathingspon-taneously. N Engl J Med 1996; 335:1864–9.5. Kress JP, Pohlman AS, O’Connor MF, HallJB. Daily interruption of sedative infusions incritically ill patients undergoing mechanicalventilation. N Engl J Med 2000; 342:1471–7.6. vanSaeneHK,SilvestriL,delaCalMA,BainesP. The emperor’s new clothes: the fairy talecontinues. J Crit Care 2009; 24:149–52.7. Alexiou VG, Ierodiakonou V, Dimopoulos G,FalagasME.Impact of patientpositionontheincidence of ventilator-associated pneumo-nia: a meta-analysis of randomized con-trolled trials. J Crit Care 2009; 24:515–22.8. Liberati A, D’Amico R, Pifferi S, Torri V,Brazzi L, Parmelli E. Antibiotic prophylaxistoreducerespiratorytractinfections and mor-tality in adults receiving intensive care. Co-chrane Database Syst Rev 2009; doi:10.1002/14651858.CD000022.pub3.9. Herzig SJ, Howell MD, Ngo LH, Marcanto-nio ER. Acid-suppressive medication useand the risk for hospital-acquired pneumo-nia. JAMA 2009; 301:2120–8.10. Klompas M, Speck K, Howell MD, GreeneLR, Berenholtz SM. Reappraisal of routineoral care with chlorhexidine gluconate forpatients receiving mechanical ventilation:systematic review and meta-analysis. JAMAIntern Med 2014; 174:751–61.11. Price R, MacLennan G, Glen J. Selective di-gestive or oropharyngeal decontaminationand topical oropharyngeal chlorhexidine forprevention of death in general intensivecare: systematic review and network meta-analysis. BMJ 2014; 348:g2197.12. Stevens JP, Kachniarz B, Wright SB, et al.When policy gets it right: variability in U.S.hospitals’ diagnosis of ventilator-associatedpneumonia. Crit Care Med 2014; 42:497–503.13. Tejerina E, EstebanA, Fernandez-Segoviano P,et al. Accuracy of clinical deﬁnitions of venti-lator-associated pneumonia: comparison withautopsy ﬁndings. J Crit Care 2010; 25:62–8.14. Klompas M. The paradox of ventilator-associated pneumonia prevention measures.Crit Care 2009; 13:315.15. Bonten MJ. Healthcare epidemiology:Ventilator-associated pneumonia: preventingthe inevitable. Clin Infect Dis 2011; 52:115–21.16. Bouadma L, Wolff M, Lucet JC. Ventilator-associated pneumonia and its prevention.Curr Opin Infect Dis 2012; 25:395–404.17. Klompas M, Branson R, Eichenwald EC, et al.Strategies to prevent ventilator-associatedpneumonia in acute care hospitals: 2014 up-date. Infect Control Hosp Epidemiol 2014;35:915–36.18. Buelow E, Gonzalez TB, Versluis D, et al. Ef-fects of selective digestive decontamination(SDD) on the gut resistome. J AntimicrobChemother 2014; 69:2215–23.19. Oostdijk EA, de Smet AM, Blok HE, et al.Ecological effects of selective decontamina-tion on resistant Gram-negative bacterial col-onization. Am J Respir Crit Care Med 2010;181:452–7.20. Daneman N, Sarwar S, Fowler RA, Cuthbert-son BH. Effect of selective decontaminationon antimicrobial resistance in intensive careunits: a systematic review and meta-analysis.Lancet Infect Dis 2013; 13:328–41.21. Neuhauser MM, Weinstein RA, Rydman R,Danziger LH, Karam G, Quinn JP. Anti-biotic resistance among gram-negative bacilliin US intensive care units: implications forﬂuoroquinoloneuse.JAMA2003; 289:885–8.22. Ong DS, Jongerden IP, Buiting AG, et al. An-tibiotic exposure and resistance developmentin Pseudomonas aeruginosa and Entero-bacter species in intensive care units. CritCare Med 2011; 39:2458–63.23. Oostdijk EA, de Smet AM, Bonten MJ. Ef-fects of decontamination of the digestivetract and oropharynx in intensive care unitpatients on 1-year survival. Am J RespirCrit Care Med 2013; 188:117–20.24. Houben AJ, Oostdijk EA, van der Voort PH,Monen JC, Bonten MJ, van der Bij AK. Selec-tive decontamination of the oropharynx andthe digestive tract, and antimicrobial resis-tance: a 4 yearecological studyin 38 intensivecare units in the Netherlands. J AntimicrobChemother 2014; 69:797–804.78 ￿ CID 2015:60 (1 January) ￿ EDITORIAL COMMENTARY

Editorial Commentary: Evidence vs Instinct for Pneumonia Prevention in Hospitalized Patients

http://dash.harvard.edu/bitstream/handle/1/13581195/4264582.pdf?sequence=1

Editorial Commentary: Evidence vs Instinct for Pneumonia Prevention in Hospitalized Patients

Abstract

Similar works

Full text

Available Versions

Harvard University - DASH