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REVIEW
New Antibiotics for Hospital-acquired pneumonia
1
Consultant in Respiratory Medicine, 6th Respiratory Department, Sotiria Chest Diseases Hospital, Athens, Greece
Corresponding author
Adamantia Liapikou
Respiratory Medicine, 6th Respiratory Department, Sotiria Chest Diseases Hospital, 152 Mesogion Avenue, GR-11527, Athens, Greece
Respiratory Medicine, 6th Respiratory Department, Sotiria Chest Diseases Hospital, 152 Mesogion Avenue, GR-11527, Athens, Greece
Pneumon 2019;32(3):89-100
KEYWORDS
ABSTRACT
Introduction:
Hospital-acquired pneumonia is the most common life-threatening hospital-acquired infection, and the majority of cases (80%) are associated with mechanical ventilation. Once pneumonia develops, the appropriateness of the initial antibiotic regimen is a vital determinant of outcome.
Areas Covered:
In this review we summarize the actual situation of new antibiotics for treatment of HAP and VAP. This article covers medical literature published in English language since 2000 until February 2019, on "hospital pneumonia", identified using PubMed and www.clinicaltrial.gov. The search terms used were "ventilator associated pneumonia", "resistance", "therapy" and "new antibiotics"
Expert Opinion:
Newer drugs approved for the combat of MDR pathogens for hospital pneumonia include cephalosporins active against MRSA and β-lactamases and as: ceftolozane combined with avibactam and ceftazidime with tazobactam. Other antibiotics active against ESBL are the combinations of carbapenems Cilastatin/imipenem/relebactam and meropenem/ Vaborbactam, plazomicin a semisynthetic derivative of sisomycin, and a new cephalosporine cefiderocol. Pneumon 2019, 32(3):89-100.
Hospital-acquired pneumonia is the most common life-threatening hospital-acquired infection, and the majority of cases (80%) are associated with mechanical ventilation. Once pneumonia develops, the appropriateness of the initial antibiotic regimen is a vital determinant of outcome.
Areas Covered:
In this review we summarize the actual situation of new antibiotics for treatment of HAP and VAP. This article covers medical literature published in English language since 2000 until February 2019, on "hospital pneumonia", identified using PubMed and www.clinicaltrial.gov. The search terms used were "ventilator associated pneumonia", "resistance", "therapy" and "new antibiotics"
Expert Opinion:
Newer drugs approved for the combat of MDR pathogens for hospital pneumonia include cephalosporins active against MRSA and β-lactamases and as: ceftolozane combined with avibactam and ceftazidime with tazobactam. Other antibiotics active against ESBL are the combinations of carbapenems Cilastatin/imipenem/relebactam and meropenem/ Vaborbactam, plazomicin a semisynthetic derivative of sisomycin, and a new cephalosporine cefiderocol. Pneumon 2019, 32(3):89-100.
REFERENCES (93)
1.
American Thoracic Society, Infectious Diseases Society of America. Guidelines for the management of adults with hospitalacquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005; 171:388–416.
2.
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; pii: ciw353.
3.
Klevens RM, Edwards JR, Richards CL Jr, et al. Estimating health care-associated infections and deaths in U.S. hospitals, 2002. Public Health Rep 2007; 122:160–6.
4.
Tablan OC, Anderson LJ, Besser R, Bridges C, Hajjeh R; CDC; Healthcare Infection Control Practices Advisory Committee. Guidelines for preventing health-care–associated pneumonia, 2003: recommendations of CDC and the Healthcare Infection Control Practices Advisory Committee. MMWR Recomm Rep 2004; 53(RR-3):1–36.
5.
Barbier F, Andremont A, Wolff M, Bouadma L. Hospital-acquired pneumonia and ventilator-associated pneumonia: recent advances in epidemiology and management. Curr Opin Pulm Med 2013; 19:216-28.
6.
Kollef MH, Shorr A, Tabak YP, Gupta V, Liu LZ, Johannes RS. Epidemiology and outcomes of health-care-associated pneumonia: results from a large US database of culture-positive pneumonia. Chest 2005; 128:e3854-e3862.
7.
Weber DJ, Rutala WA, Sickbert-Bennett EE, et al. Microbiology of ventilator-associated pneumonia compared with that of hospital-acquired pneumonia. Infect Control Hosp Epidemiol 2007; 28:825-31.
8.
Sievert DM, Ricks P, Edwards JR, et al. Antimicrobial-resistant pathogens associated with healthcare-associated infections: summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2009–2010. Infect Control Hosp Epidemiol 2013; 34:1–14.
9.
Martin-Loeches I, Torres A, Rinaudo M, et al. Resistance patterns and outcomes in intensive care unit (ICU)-acquired pneumonia. Validation of European Centre 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.
10.
Tumbarello M, De Pascale G, Trecarichi EM, et al. Clinical outcomes of Pseudomonas aeruginosa pneumonia in intensive care unit patients. Intensive Care Med 2013; 39:682–92.
11.
Kollef MH, Chastre J, Fagon JY, et al. Global prospective epidemiologic and surveillance study of ventilator-associated pneumonia due to Pseudomonas aeruginosa. Crit Care Med 2014; 42:2178–87.
12.
Tedja R, Nowacki A, Fraser T, et al. The impact of multidrug resistance on outcomes in ventilator-associated pneumonia. Am J Infect Control 2014; 42:542–5.
13.
Bonten MJ, Kollef MH, Hall JB. Risk factors for ventilator-associated pneumonia: from epidemiology to patient management. Clin Infect Dis 2004; 38:1141-9.
14.
Shorr AF, Zilberberg MD, Micek ST, Kollef MH. Outcomes associated with bacteremia in the setting of methicillin-resistant Staphylococcus aureus pneumonia: a retrospective cohort study. Crit Care 2015; 19:312.
15.
Torres A, Ewig S, Lode H, et al. Defining, treating and preventing hospital acquired pneumonia: European perspective. Intensive Care Med 2009; 35:9-29.
16.
Iregui M, Ward S, Sherman G, Fraser VJ, Kollef MH. Clinica importance of delays in the initiation of appropriate antibiotic treatment for ventilator-associated pneumonia. Chest 2002; 122:262–8.
17.
Alvarez-Lerma F. Modification of empiric antibiotic treatment in patients with pneumonia acquired in the intensive care unit. ICU-acquired pneumonia study group. Intensive Care Med 1996; 22:387–94.
18.
Ferrer R, Martin-Loeches I, Phillips G, et al. Empiric antibiotic treatment reduces mortality in severe sepsis and septic shock from the first hour: results from a guideline-based performance improvement program. Crit Care Med 2014; 42:1749–55.
19.
Leroy O, d’Escrivan T, Devos P, et al. Hospital acquired pneumonia in critically ill patients: factors associated with episodes due to imipenem-resistant organisms. Infection 2005; 33:129–35.
20.
Joshi M, Metzler M, McCarthy M, et al. Comparison of piperacillin/ tazobactam and imipenem/cilastatin, both in combination with tobramycin, administered every 6h for treatment of nosocomial pneumonia. Respir Med 2006;100:1554-65.
21.
Chung DR, Song JH, Kim SH, et al. High prevalence of multidrugresistant nonfermenters in hospital-acquired pneumonia in Asia. Am J Resp Crit Care Med 2011; 184:1409–17.
22.
Sader HS, Farrell DJ, Flamm RK, Jones RN. Antimicrobial susceptibility of Gram-negative organisms isolated from patients hospitalized with pneumonia in US and European hospitals: results from the SENTRY Antimicrobial Surveillance Program, 2009-2012. Int J Antimicrob Agents 2014; 43:328-34.
23.
Seligman R, Ramos-Lima LF, Oliveira VD, et al. Risk factors for infection with multidrug-resistant bacteria in nonventilated patients with hospital-acquired pneumonia. J Bras Pneumol 2013; 39:339–48.
24.
Magiorakos AP, Srinivasan A, Carey RB, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 2012; 18:268-81.
25.
Rello J, Ulldemolins M, Lisboa T, et al. Determinants of prescription and choice of empirical therapy for hospital-acquired and ventilator-associated pneumonia. Eur Respir J 2011; 37:1332-9.
26.
Stolz D, Smyrnios N, Eggimann P, et al. Procalcitonin for reduced antibiotic exposure in ventilator-associated pneumonia: a randomized study. Eur Respir 2009; 34:1364–75.
27.
Liapikou A, Torres A. Emerging drugs on methicillin-resistant Staphylococcus aureus. Expert Opin Emerg Drugs 2013; 18:291- 305.
28.
Denys GA, Callister SM, Dowzicky MJ. Antimicrobial susceptibility among gram negative isolates collected in the USA between 2005 and 2011 as part of the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.). Ann Clin Microbiol Antimicrob 2013; 12:24. doi: 10.1186/1476-0711-12-24.
29.
Stein GE, Babinchak T. Tigecycline: an update. Diagn Microbiol Infect Dis 2013; 75:331-6.
30.
Hirsch EB, Tam VH. Detection and treatment options for Klebsiella pneumoniae carbapenemases (KPCs): an emerging cause of multidrug-resistant infection. The Journal of Antimicrobial Chemotherapy 2010; 65:1119-25.
31.
Freire AT, Melnyk V, Kim MJ, et al. Comparison of tigecycline with imipenem/cilastatin for the treatment of hospital-acquired pneumonia. Diagn Microbiol Infect Dis 2010; 68:140–51.
32.
US Food and Drug Administration (FDA). FDA drug safety communication: FDA warns of increased risk of death with IV antibacterial Tygacil (tigecycline) and approves new boxed warning. http://www.fda.gov/Drugs/DrugS... (Accessed on October 09, 2013).
33.
Ramirez J, Dartois N, Gandjini H, et al. Randomized phase 2 trial to evaluate the clinical efficacy of two high-dosage tigecycline regimens versus imipenem cilastatin for treatment of hospital-acquired pneumonia. Antimicrob Agents Chemother 2013; 57:1756–62.
34.
EMA. Questions and answers on the review of Tygacil (tigecycline). Outcome of a renewal procedure CMA/121925/2011, EMA/H/C/000644/R/54. Available from: http://www.ema.europa.eu/docs/... /000644/ WC500102228.pdf.
35.
Liapikou A, Dimakou K, Toumbis M. Telavancin in the treatment of Staphylococcus aureus hospital-acquired and ventilatorassociated pneumonia: clinical evidence and experience. Ther Adv Respir Dis 2016.
36.
Mendes RE, Sader HS, Farrell DJ, Jones RN. Worldwide appraisal and update (2010) of telavancin activity tested against a collection of Gram-positive clinical pathogens from five continents. Antimicrob Agents Chemother 2012; 56:3999–4004.
37.
Rubinstein E, Lalani T, Corey GR, et al; ATTAIN Study Group. Telavancin versus vancomycin for hospital acquired pneumonia due to gram-positive pathogens. Clin Infect Dis 2011; 52:31–40.
38.
Liapikou A, Cilloniz C, Mensa J, Torres A. New antimicrobial approaches to gram positive respiratory infections. Pulm Pharmacol Ther 2015; 32:137-43.
39.
Farrell DJ, Flamm RK, Sader HS, Jones RN. Ceftobiprole activity against over 60,000 clinical bacterial pathogens isolated in Europe, Turkey, and Israel from 2005 to 2010. Antimicrob Agents Chemother 2014; 58:3882–8.
40.
Awad SS, Rodriguez AH, Chuang YC, et al. A Phase 3 Randomized Double-Blind Comparison of Ceftobiprole Medocaril Versus Ceftazidime Plus Linezolid for the Treatment of Hospital-Acquired Pneumonia. Clin Infect Dis 2014; 59:51-61.
41.
Lagacé-Wiens PR, Rubinstein E. Pharmacokinetic and pharmacodynamics evaluation of ceftobiprole medocaril for the treatment of hospital-acquired pneumonia. Expert Opin Drug Metab Toxicol 2013; 9:789-99.
42.
Actavis plc. Actavis Receives U.S. FDA Approval for AVYCAZ™ (CEFTAZIDIME-AVIBACTAM). 2015 Feb 25, Available at: http://www.prnewswire.com/news.... Accessed 2015 March 3.
43.
Aktas Z, Kayacan C, Oncul O. In vitro activity of avibactam (NXL104) in combination with betalactams against Gramnegative bacteria, including OXA-48 beta-lactamase-producing Klebsiella pneumoniae. International Journal of Antimicrobial agents 2012; 39:86-9.
44.
Hackel M, Kazmierczak K, Hoban D, et al. An assessment of the in vitro activity of ceftazidime-avibactam against multi-drug resistant Klebsiella spp. Collected in the INFORM Global Surveillance Study (2012-2014). Antimicrob Agents Chemother 2016; pii: AAC.02841-15.
47.
Solomkin J, Hershberger E, Miller B, et al. Ceftolozane/tazobactam plus metronidazole for complicated intra-abdominal infections in an era of multidrug resistance: results from a randomized, double-blind, phase 3 trial (ASPECT-cIAI). Clin Infect Dis 2015; 60:1462–71.
48.
Sader HS, Rhomberg PR, Farrell DJ, Jones RN. Antimicrobial Activity of CXA-101, a Novel Cephalosporin Tested in Combination with Tazobactam against Enterobacteriaceae, Pseudomonas aeruginosa, and Bacteroides fragilis Strains Having Various Resistance Phenotypes. Antimicrobial Agents and Chemotherapy, 2011; 55:2390–4.
49.
Hong MC, Hsu DI, Bounthavong M. Ceftolozane/tazobactam: a novel antipseudomonal cephalosporin and b-lactamaseinhibitor combination. Infect Drug Resist 2013; 6:215–23.
50.
Juan C, Zamorano L, Perez JL, Ge Y, Oliver A. Activity of a new antipseudomonal cephalosporin, CXA-101 (FR264205), against carbapenem- resistant and multidrug-resistant Pseudomonas aeruginosa clinical strains. Antimicrob. Agents Chemother 2010; 54:846–51.
51.
Cubist Pharmaceuticals Holdings LLC. Study of Intravenous Ceftolozane/Tazobactam Compared to Piperacillin/Tazobactam in Ventilator- Associated Pneumonia. Available from: https://clinicaltrials.gov/ct2.... NLM identifier: NCT01853982. Accessed February 28, 2015.
52.
Munita JM, Aitken SL, Miller WR, et al. Multicenter evaluation of ceftolozane /tazobactam for serious infections caused by carbapenem-resistant Pseudomonas aeruginosa. Clin Infect Dis 2017;65:158–61.
53.
Xipell M, Bodro M, Marco F, et al. Successful treatment of three severe MDR or XDR Pseudomonas aeruginosa infections with ceftolozane/tazobactam. Future Microbiol 2017;12:1323–6.
54.
Rybak JM, Roberts K. Tedizolid Phosphate: a Next-Generation Oxazolidinone. Infect Dis Ther 2015; 4:1–14.
55.
Shaw KJ, Poppe S, Schaadt R, et al. In vitro activity of TR-700, the antibacterial moiety of the prodrug TR-701, against linezolidresistant strains. Antimicrob Agents Chemother 2008; 52:4442-7.
56.
Flanagan S, Passarell J, Lu Q, et al. Tedizolid population pharmacokinetics, exposure response, and target attainment. Antimicrob Agents Chemother 2014;58:6462–70.
57.
Schaadt R, Sweeney D, Shinabarger D, Zurenko G. In vitro activity of TR-700, the active ingredient of the antibacterial prodrug TR-701, a novel oxazolidinone antibacterial agent. Antimicrob Agents Chemother 2009; 53:3236–9.
58.
Livermore DM, Mushtaq S, Warner M, Woodford N. Activity of oxazolidinone TR-700 against linezolid-susceptible and -resistant staphylococci and enterococci. J Antimicrob Chemother 2009; 63:713–5.
59.
Zhanel GG, Love R, Adam H, et al. Tedizolid: a novel oxazolidinone with potent activity against multidrug-resistant gram-positive pathogens. Drugs 2015;75:253-70.
61.
Karaiskos I, Giamarellou H. Multidrug-resistant and extensively drug-resistant Gram-negative pathogens: current and emerging therapeutic approaches. Expert Opin Pharmacother 2014; 15:1351–70.
62.
Landman D, Kelly P, Bäcker M, et al. Antimicrobial activity of a novel aminoglycoside, ACHN-490, against Acinetobacter baumannii and Pseudomonas aeruginosa from New York City. J Antimicrob Chemother 2011; 66:332-4.
63.
García-Salguero C, Rodríguez-Avial I, Picazo JJ, Culebras E. Can plazomicin alone or in combination be a therapeutic option against carbapenem-resistant Acinetobacter baumannii? Antimicrobial Agents and Chemotherapy 2015; 59:5959-66.
64.
Wright H, Bonomo RA, Paterson DL. New agents for the treatment of infections with Gram-negative bacteria: restoring the miracle or false dawn? Clin Microbiol Infect 2017; 23:704–12.
65.
Zhanel GG, Lawson CD, Zelenitsky S, et al. Comparison of the next generation aminoglycoside plazomicin to gentamicin, tobramycin and amikacin. Expert Rev Anti Infect Ther 2012; 10:459-73.
66.
Pankuch GA, Lin G, Kubo A, et al. Activity of ACHN-490 tested alone and in combination with other agents against Pseudomonas aeruginosa. Antimicrob. Agents Chemother 2011; 55:2463–5.
67.
Cass RT, Brooks CD, Havrilla NA, et al. Pharmacokinetics and safety of single and multiple doses of ACHN-490 injection administered intravenously in healthy subjects. Antimicrob Agents Chemother 2011; 55:5874-80.
69.
U.S. Food and Drug Administration Antimicrobial Drugs Advisory Committee. FDA briefing document: plazomicin sulfate injection (NDA 210303). Available from https://www.fda.gov/downloads/.... Accessed August 10, 2018.
70.
Drugs@FDA: FDA Approved Drug Products”. www.accessdata.fda.gov. pp. New Drug Application (NDA): 210303. Retrieved 2019-01-22.
71.
Castanheira M, Rhomberg PR, Flamm RK, Jones RN. Effect of the β-lactamase Inhibitor Vaborbactam Combined with Meropenem When Tested Against Serine-CarbapenemaseProducing Enterobacteriaceae. Antimicrob Agents Chemother 2016; pii: AAC.00711-16.
72.
Lomovskaya O, Sun D, Rubio-Aparicio D, et al. Vaborbactam: spectrum of beta-lactamase inhibition and impact of resistance mechanisms on activity in Enterobacteriaceae. Antimicrob Agents Chemother 2017;61:e00989–17.
73.
Wenzler E, Gotfried MH, Loutit JS, et al. Plasma, epithelial lining fluid, and alveolar macrophage concentrations of meropenem- RPX7009 in healthy adult subjects. Antimicrob Agents Chemother 2015;59:7232–9.
74.
Vabomere [package insert]. Parsippany, NJ: The Medicines Company; 2017. Available from: https://dailymed.nlm.nih.gov/d... =580db23f-c655-3049- e053-2a91aa0ad616.
76.
Hirsch EB, Ledesma KR, Chang K-T, et al. In vitro activity of MK-7655, a novel b-lactamase inhibitor, in combination with imipenem against carbapenem-resistant Gram negative bacteria. Antimicrob Agents Chemother 2012; 56:3753–7.
77.
Lapuebla A, Abdallah M, Olafisoye O, et al. Activity of Imipenem with Relebactam against Gram-Negative Pathogens from New York City. Antimicrobial Agents and Chemotherapy 2015; 59:5029-31. DOI: 10.1128/AAC.00830-15.
82.
Basseti M, Righi E, Russo A, Carnelutti A. New antibiotics for pneumonia. Clin Chest Med 2018;39:853-69.
83.
Falagas ME, Skalidis T, Vardakas KZ, et al. Activity of cefiderocol (S-649266) against carbapenem-resistant Gram-negative bacteria collected from inpatients in Greek hospitals. J Antimicrob Chemother 2017; 72:1704–8.
84.
Hackel MA, Tsuji M, Yamano Y, et al. In vitro activity of the siderophore cephalosporin, cefiderocol, against a recent collection of clinically relevant Gram-negative bacilli from North America and Europe, including carbapenem non-susceptible isolates: The SIDEROWT- 2014 Study. Antimicrob. Agents Chemother 2017; 61:1–22.
85.
Saisho Y, Katsube T, White S, et al. Pharmacokinetics, Safety, and Tolerability of Cefiderocol, a Novel Siderophore Cephalosporin for Gram-Negative Bacteria, in Healthy Subjects. Antimicrob Agents Chemother 2018; 62(3). pii: e02163-17. doi:10.1128/ AAC.02163-17.
86.
Avery LM, Nicolau DP. Investigational drugs for the treatment of infections caused by multidrug-resistant Gram-negative bacteria. Expert Opin Investig Drugs 2018;27:325-38.
87.
Murepavadin (POL7080) [Internet]. Polyphor Ltd. [cited 2017 Nov 7]. Available from: https://www.polyphor.com/pol70....
88.
Armaganidis A, Frantzeskaki F, Diakaki C, et al. Pharmacokinetic and efficacy analysis of murepavadin co-administered with standard-of-care in a phase II study in patients with ventilatorassociated pneumonia due to suspected or documented P. aeruginosa infection. Poster session presented at: ECCMID; 2017; Vienna, Austria.
89.
Arnold HM, Sawyer AM, Kollef MH. Use of adjunctive aerosolized antimicrobial therapy in the treatment of Pseudomonas aeruginosa and Acinetobacter baumannii ventilator-associated pneumonia. Respir Care 2012; 57:1226–33.
90.
Lu Q, Yang J, Liu Z, Gutierrez C, Aymard G, Rouby JJ; Nebulized Antibiotics Study Group. Nebulized ceftazidime and amikacin in ventilator-associated pneumonia caused by Pseudomonas aeruginosa. Am J Respir Crit Care Med 2011; 184:106–15.
91.
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.
92.
Zampieri FG, Nassar AP, Gusmao-Flores D, et al. Nebulized antibiotics for ventilator-associated pneumonia: a systematic review and meta-analysis. Critical Care 2015; 19:150. doi:10.1186/ s13054-015-0868-y.
93.
Bassetti M, Luyt CE, Nicolau DP, Pugin J. Characteristics of an ideal nebulized antibiotic for the treatment of pneumonia in the intubated patient. Ann Intensive Care 2016;6:35. doi: 10.1186/s13613-016-0140-x.
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