Hospital-acquired pneumonia (HAP) is a common cause of
nosocomial infection associated with significant morbidity and
mortality. New clinical practice guidelines for the management of adults with hospital-acquired pneumonia have been
published in 2016 by the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS). This review
focuses on the recent recommendations and their limitations.
We also focus on new therapeutic options that might improve
the treatment and outcomes of these patients

Cardozo Espinola, Celia

Cillóniz, Catia

Garcia Vidal, Carolina

Puerta Alcalde, Pedro

Torres Martí, Antoni

Vacas Córdoba, Miguel

Revista Española de Quimioterapia

English

Puerta-Alcalde, Pedro

Diposit Digital de la Universitat de Barcelona

Hospital acquired pneumonia (HAP) is defined as an in-flammatory process in lung tissue caused by infectious patho-gens that is not present at the time of hospital admission and occurring 48 hours or more post admission1.It represents the second most prevalent hospital-acquired infection2, and is an important concern for national public health system due to its high morbidity and mortality as well as the huge amount of health resources that consumes. It is important to note the differences between HAP and ventila-tor-associated pneumonia (VAP). VAP is defined as the pneu-monia that arises more than 48 to 72 hours after endotracheal intubation. Despite this infection is also a nosocomial pneu-monia, in the next lines we will refer to HAP exclusively in pa-tients without intubation.There are different challenges for physicians in the treat-ment of HAP. There is very little current information regard-ing the aetiology of HAP. Most data concerning the aetiology of nosocomial pneumonia refer especially to VAP population. A recent review published by our group describes that up to 60% of the cases of HAP are caused by gram-negative bacil-li. Pseudomonas aeruginosa (24%) and Klebsiella spp. (11%) were the most frequently microorganisms isolated. The most frequent gram-positive pathogen associated with HAP was Staphylococcus aureus, accounting for 30% of the cases1. Re-markably, the risk factors for multidrug resistant HAP are not well defined. Antibiotic resistance is a global health problem worldwide, especially in those infections caused by gram-neg-ative bacilli. The infections caused by these multidrug resistant strains receive often inappropriate antimicrobial therapy and it might negatively impact on outcomes.  New clinical practice guidelines for the management of adults with hospital-acquired pneumonia have been published in 2016 by the Infectious Diseases Society of America (IDSA) and American Thoracic Society (ATS)3. In these guidelines, the distinction between “early onset” pneumonia (occurs in the first 96 hours of hospital admission) and “late onset” pneumonia ABSTRACTHospital-acquired pneumonia (HAP) is a common cause of nosocomial infection associated with significant morbidity and mortality. New clinical practice guidelines for the manage-ment of adults with hospital-acquired pneumonia have been published in 2016 by the Infectious Diseases Society of Ameri-ca (IDSA) and the American Thoracic Society (ATS). This review focuses on the recent recommendations and their limitations. We also focus on new therapeutic options that might improve the treatment and outcomes of these patients.Tratamiento empírico de la neumonía nosocomial en adultos: luces y sombras de las guías de práctica clínica de la ATS/IDSA de 2016RESUMENLa neumonía nosocomial es una causa frecuente de in-fección intrahospitalaria y tiene una elevada morbilidad y mortalidad. En el año 2016 se ha publicado una nueva guía de práctica clínica para el manejo de la neumonía nosocomial en adultos, elaborada por la Infectious Diseases Society of Amer-ica (IDSA) y la American Thoracic Society (ATS). Esta revisión comenta nuestra opinión sobre las nuevas recomendaciones y sus limitaciones, así como en las nuevas opciones terapéuticas disponibles que podrían mejorar el tratamiento y pronóstico de estos pacientes.Empirical treatment of adults with hospital-acquired pneumonia: lights and shadows of the 2016 Clinical Practice ATS/IDSA Guidelines1Department of Internal Medicine, Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Spain. 2Department of Infectious Diseases, Hospital Clínic, Barcelona, Spain.3Department of Pneumology, Institut Clinic del Tórax, Hospital Clinic of Barcelona - Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona (UB) - SGR 911- Ciber de Enfermedades Respiratorias (Ciberes) Barcelona, Spain. Miguel Vacas-Córdoba1Celia Cardozo-Espinola2Pedro Puerta-Alcalde2Cati Cilloniz3Antoni Torres3Carolina García-Vidal2Correspondence:Celia Cardozo-EspinolaDepartment of Infectious Diseases, Hospital Clínic. Carrer Villarroel 170, 08036, Barcelona, Spain. Phone: +34-932275430. Fax: +34-934514438. E-mail: cgcardoz@clinic.catUpdate in Main Infectious SyndromesRev Esp Quimioter 2017;30 (Suppl. 1): 30-33 30Empirical treatment of adults with hospital-acquired pneumonia: lights and shadows of the 2016 Clinical Practice ATS/IDSA GuidelinesM. Vacas-Córdoba, et al.Rev Esp Quimioter 2017;30 (Suppl. 1): 30-33 31the empirical antibiotic therapy for patients with HAP: risk of MDR infection and severity of disease. After the review of sev-eral articles, the authors identify the use of prior intravenous antibiotic treatment within 90 days as the only risk factor for MDR HAP.  Other factors such as the existence of comorbid-ity, recent hospital admission, the use of prior oral antibiot-ics, current hospitalization in an area of high prevalence of multi-drug resistances or previous colonization by multi-drug resistant microorganisms were not taken into account. Those patients who require mechanical ventilation or present shock at the time of diagnosis were categorized as patients who had high risk of mortality. Some measures such as empirical double (appears after >96 hours) has been removed. This division was based on the fact that within the first days of hospital admission, gram-positive cocci still predominate on the flora of the respira-tory system. After 5-7 days of illness, oropharynx fibronectin disappears and some receptors that allow the gram-negative rods colonization are exposed. Antibiotic pressure selects mul-tiresistant strains and P. aeruginosa colonization4. Recent stud-ies have questioned the relationship between the timing of no-socomial pneumonia and the risk of multidrug-resistant (MDR) pathogens. However, most of these researches were focused on VAP5,6. The 2016 guidelines on HAP3 remark two factors to decide Not at high risk of mortality and no factors increasing the likelihood of MRSANot at high risk of mortality but with factors increasing the likelihood of MRSAHigh risk of mortality or receipt of intravenous antibiotics during the prior 90 daysOne of the following: One of the following: Two of the following, avoid 2 β-lactams:Piperacilin-tazobactam 4.5 g IV q6h Piperacilin-tazobactam 4.5 g IV q6h Piperacilin-tazobactam 4.5 g IV q6hOR OR ORCefepime 2 g IV q8h Cefepime or ceftazidime 2 g IV q8h Cefepime or ceftazidime 2 g IV q8hOR OR OR Levofloxacin 750 mg IV daily Levofloxacin 750 mg IV dailyCiprofloxacin 400 mg IV q8hLevofloxacin 750 mg IV dailyCiprofloxacin 400 mg IV q8hOR ORImipenem 500 mg IV q6hMeropenem 1 g IV q8hImipenem 500 mg IV q6hMeropenem 1 g IV q8hImipenem 500 mg IV q6hMeropenem 1 g IV q8hOR ORAztreonam 2 g IV q8h Amikacin 15-20 mg/kg IV dailyGentamicin 5-7 mg/kg IV dailyTobramycin 5-7 mg/kg IV dailyORAztreonam 2 g IV q8hPlus:Vancomycin 15 mg/kg IV q8-12h with goal to target 15-20 mg/mL trough level (consider a loading dose of 25-30 mg/kg x 1 for severe illnessPlus:Vancomycin 15 mg/kg IV q8-12h with goal to target 15-20 mg/mL trough level (consider a loading dose of 25-30 mg/kg x 1 for severe illnessOR ORLinezolid 600 mg IV q12h Linezolid 600 mg IV q12hIf MRSA coverage is not going to be used, include coverage for MSSA. Options include:Piperacilin-tazobactam, cefepime, levofloxacin, imipenem, meropenem. Oxacilin, nafcillin, and cefazolin are preferred for the treatment of proven MSSA, but would ordinarily not be used in an empiric regimen for HAP.If patient has severe penicillin allergy and aztreonam is going to be used instead of any β-lactam-based antibiotic, include coverage for MSSA.Table 1  Recommended initial empiric antibiotic therapy for hospital-acquired pneumonia  (non-ventilator-associated pneumonia) (adapted from reference 3)Empirical treatment of adults with hospital-acquired pneumonia: lights and shadows of the 2016 Clinical Practice ATS/IDSA GuidelinesM. Vacas-Córdoba, et al.Rev Esp Quimioter 2017;30 (Suppl. 1): 30-33 32against gram-positive pathogens. It binds to different PBP, in-cluding PBP2a, making it active against methicillin-resistant S. aureus (MRSA). It is one of the antibiotics with greater bacteri-cidal effect against gram-positive and has an inmunomodula-tory activity by inhibiting some toxins. As most beta-lactams, it does not have major side effects.Tedizolid is an oxazolidinone with a long half-life and few significant side effects. A double-blind randomized clinical trial is currently underway to compare tedizolid versus linezolid in patients with HAP9.Finally, dalbavancin is a recently approved glycopeptide used to treat infections caused by S. aureus and MRSA. Its main advantage is its dosage (once a week) and its few side ef-fects10. Further information is needed to recommend this drug in patients with HAP.In conclusion, HAP is a serious and difficult to treat illness. Some new therapeutic options that might improve the treat-ment and prognosis of patients who develop this infection have recently appeared. Further studies are needed to define high risk patients for MDR-HAP and to check if new antibiotics have any impact to improve outcomes.ACKNOWLEDGEMENTSC.C. is recipient of ERS Short Term Fellowship and Post-doctoral Grant “Strategic plan for research and innovation in health-PERIS 2016-2020”.REFERENCES1. Cilloniz C, Martín-Loeches I, García-Vidal C, San José A, Torres A. Microbial etiology of pneumonia: Epidemiology, diagnosis and re-sistance patterns. Int J Mol Sci 2016; 17:E2120.2. Magill SS, Edwards JR, Fridkin SK. Emerging Infections Program Healthcare-Associated Infections Antimicrobial Use Prevalence Survey Team. Survey of health  care-associated infections. N Engl J Med 2014; 370:2542–3.  3. Kalil AC, Metersky ML, Klompas M, Muscedere J, Sweeney DA, Palmer LB, et al. Management of adults with hospital-aquired 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: e61-111.4. 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, 388–416.5. Giantsou E, Liratzopoulos N, Efraimidou E, Panopoulo M, Ale-popoulo E, Kartali-Ktenidou S, et al. Both early-onset and late-on-set ventilator-associated pneumonia are caused mainly by po-tentially multiresistant bacteria. Intensive Care Med. 2005, 31, 1488–94. 6. Ibrahim EH, Ward S, Sherman G, Kollef MH. A comparative analysis of patients with early-onset vs. late-onset nosocomial pneumonia in the ICU setting. Chest. 2000, 117, 1434–42.coverage treatment for gram-negative bacilli are recommend-ed only for these patients.Empirical antibiotic treatments recommended by new guidelines for the different patient subgroups with HAP are shown in the table 1.We have some concerns about these recommendations. Firstly, some of the empirical antibiotic treatments proposed are not optimal to treat aspiration pneumonia. We would like to point out that this aetiology is important to consider in older patients, in those with cerebrovascular diseases and/or impaired consciousness at presentation and/or in those pa-tients with swallowing difficulties. Secondly, we think that an initial empirical treatment with levofloxacin o ciprofloxacin as a unique therapy to treat gram-negative bacilli might be in-appropriate in most countries due to the high prevalence of resistant strains to these drugs7. It is also important to point out that not all drugs combinations used for gram-negative bacilli are synergistic and/or appropriate. Thirdly, the empirical use of vancomycin might be severely compromised, given the profile of patients who are currently admitted to the hospital (elderly and with high comorbidity) because of its toxicity. This fact is particularly relevant for patients receiving concomitant treatment with aminoglycosides.Finally, the 2016 guidelines on HAP suggest that antibiotic therapy should be adjusted according to the results of antibio-gram. However, we would like to emphasize that not all antibi-otics have the same bactericidal power, side effects and ability of generating resistances. All these factors should be taken in-to account when definitive treatment is selected.Five new antibiotics have been approved recently. They are not included in the new guidelines and may be useful in patients with HAP. Ceftolozane-tazobactam is a beta-lactam antibiotic with a similar chemical structure to ceftazidime. Ceftolozane is larger than ceftazidime, so it cannot be re-moved by efflux pumps. This antibiotic has also full activity against OprD mutant strains. Moreover, the addition of tazo-bactam provides activity to many class A beta-lactamases. For all these reasons, ceftolozane-tazobactam offers an excellent coverage against P. aeruginosa, even for the multi-drug resist-ant strains. In a total of 2,968 isolates of P. aeruginosa consec-utively collected from patients hospitalized with pneumonia in 59 medical centres in the USA and 15 European countries, ceftolozane-tazobactam demonstrated a greater in vitro activ-ity than currently available cephalosporins, carbapenems and piperacillin-tazobactam8. Avibactam is a new beta-lactamases inhibitor, molec-ularly very different from existing ones. This inhibitor has an intrinsic antibacterial action and a peculiar structure that pro-tects it from hydrolyzation by several beta-lactamases.  Cef-tazidime-avibactam is a novel cephalosporin/beta-lactamase inhibitor that inhibits the activities of ambler class A and C beta-lactamases and some ambler class D enzymes. This drug offers coverage for most carbapenemase producing-Entero-bacteriaceae in Spain.Ceftaroline is a new cephalosporin that has a great action Empirical treatment of adults with hospital-acquired pneumonia: lights and shadows of the 2016 Clinical Practice ATS/IDSA GuidelinesM. Vacas-Córdoba, et al.Rev Esp Quimioter 2017;30 (Suppl. 1): 30-33 337. Martín-Loeches I, Torres A, Rinaudo M, Terraneo S, de Rosa F, Ramirez P, et al. Resistance patterns and outcomes in intensive care unit (ICU)-acquired pneumonia. Validation of European Cen-tre for Disease Prevention and Control (ECDC) and the Centers for Disease Control and Prevention (CDC) classification of multidrug resistant organisms. J. Infect. 2015, 70, 213–22.8. Farrell DJ, Sader HS, Flamm RK, Jones RN. Ceftolozane/tazobac-tam activity tested against Gram-negative bacterial isolates from hospitalised patients with pneumonia in US and European medical centres (2012). Int J Antimicrob Agents. 2014; 43(6):533-9. 9. Tedizolid Phosphate (TR-701 FA) vs Linezolid for the Treatment of Nosocomial Pneumonia (MK-1986-002). https://clinicaltrials.gov/ct2/show/NCT02019420.10. Saravolatz LD, Billeter M, Zervos MJ, Chen AY, Dalovisio JR, Ku-rukularatne C. Dalbavancin: a Novel Once-Weekly Lipoglycopep-tide Antibiotic. Clin Infect Dis 2008; 46 (4): 577-83.

Empirical treatment of adults with hospital-acquired pneumonia: lights and shadows of the 2016 Clinical Practice ATS/IDSA Guidelines

http://diposit.ub.edu/dspace/bitstream/2445/145140/1/12474_5635427_06vacas.pdf

Empirical treatment of adults with hospital-acquired pneumonia: lights and shadows of the 2016 Clinical Practice ATS/IDSA Guidelines

Abstract

Similar works

Full text

Available Versions

Diposit Digital de la Universitat de Barcelona