scholarly journals MODERN APPROACHES TO TREATMENT OF PSEUDOMONAS AERUGINOSA VENTILATOR-ASSOCIATED PNEUMONIA (LITERATURE REVIEW)

2019 ◽  
Vol 72 (5) ◽  
pp. 892-896
Author(s):  
Olha A. Poda ◽  
Tetyana O. Kryuchko ◽  
Inna N. Nesina ◽  
Olha Ya. Tkachenko ◽  
Nataliia V. Kuzmenko

Introduction: Nowadays anti-microbial therapy of ventilator-associated pneumonia caused by is one of the most topical issue as a consequence of widespread multiresistant strains of causative agent and their biological peculiarity of actively formation of resistance to new antibacterial drugs. The aim is to describe modern approaches to therapy of ventilator-associated pneumonia causative agent of which is presented by Pseudomonas aureginosa . Materials and methods: An analysis and summing up of results of scientific investigations described in medical publications concerning the issues of therapy of ventilatorassociated pneumonia caused by Pseudomonas aureginosa was done. Conclusions: Despite the development of modern approaches to anti-microbial therapy of ventilator-associated pneumonia caused by Pseudomonas aeruginosa, which are also concerned with such controversial issues as correct choice of antibacterial drug, its optimal dose, and duration of this therapy, the problem of treatment of hospital-acquired infections of respiratory airways caused by Pseudomonas aeruginosa has been discussable yet and requires the further study.

2016 ◽  
Vol 38 (9) ◽  
pp. 2098-2105 ◽  
Author(s):  
Douglas J. Biedenbach ◽  
Phan Trong Giao ◽  
Pham Hung Van ◽  
Nguyen Su Minh Tuyet ◽  
Tran Thi Thanh Nga ◽  
...  

Author(s):  
O.A. Poda

Introduction. At present, antimicrobial therapy of ventilator-associated pneumonia and bacteremia caused by Pseudomonas aeruginosa is an urgent problem due to the high prevalence of microbial multiresistant strains and their ability to develop resistance to new antibacterial drugs. Materials and methods. The analysis and generalization of the results of scientific studies highlighted in fundamental medical journals related to the treatment of ventilator-associated pneumonia and bacteremia caused by Pseudomonas infection are carried out. Results. The main points in the modern approach to the effective treatment of ventilator-associated pneumonia and bacteremia caused by Pseudomonas aeruginosa include the correct empirical choice of the starting antibacterial agent in accordance with the local epidemiology of the medical setting, timely beginning of the treatment, options to combine drugs with a tendency to de-escalation to monotherapy. It is also important to choose the optimal drug in terms of its pharmacological parameters and a clear definition of the optimal therapeutic dosage. The article describes the main groups of drugs currently used in the treatment of the main clinical forms of Pseudomonas aeruginosa. Nowadays, it is recommended to combine therapy for pseudomonas ventilator-associated pneumonia and bacteremia with antipseudomonas penicillins or cephalosporins or carbapenems plus fluoroquinolones or aminoglycosides or colistin with phosphomycin. Conclusions. Despite the elaboration of the modern approaches to the antimicrobial therapy of infections caused by Pseudomonas aeruginosa, this issue is still debatable and requires further study.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S792-S792
Author(s):  
Dee Shorttidge ◽  
Lalitagauri M Deshpande ◽  
Leonard R Duncan ◽  
Jennifer M Streit ◽  
Mariana Castanheira

Abstract Background Meropenem-vaborbactam (MVB) was recently approved in Europe for the treatment of complicated UTIs, including acute pyelonephritis, complicated intra-abdominal infections, hospital-acquired bacterial pneumonia, ventilator-associated pneumonia (VAP), and bacteremia. KPC-producing Enterobacterales (ENT) isolates have disseminated worldwide. We analysed the activity of MVB and single-agent comparators against 6,846 ENT isolates from patients hospitalised with pneumonia (PHP) including VAP in European hospitals (2014–2019). Methods Among 6,846 ENT clinical isolates from PHP collected in 40 European hospitals located in 20 countries that were susceptibility (S) tested using reference broth microdilution methods. Of the carbapenem-resistant isolates submitted to whole genome sequencing, 75 carried blaKPC. ENT isolates were also characterized for an extended spectrum beta-lactamase (ESBL) phenotype as described (CLSI, 2020). EUCAST (2020) interpretive criteria were used. %S from patients in the intensive care unit (ICU), ICU patients with VAP, and non-ICU isolates were also analysed. Results The most common ENT pathogens isolated from PHP were Klebsiella pneumoniae (KPN; n=1,877) and Escherichia coli (EC; n=1,646). The %S of MVB and comparators to ENT, ICU, ICU/VAP, and non-ICU are shown in the table. Overall, 98.2% of ENT were S to MVB. For 3,218 ENT isolates from ICU patients, MVB %S was 96.6% and for 2,627 non-ICU isolates MVB %S was 98.5%. The %S of comparators for ICU vs non-ICU isolates were similar, except for levofloxacin. 29 KPC-producing isolates were from ICU (11 from VAP), 46 were from non-ICU. Most KPC-producing isolates were KPN (n=71; 54 blaKPC-3, 16 blaKPC-2 and 1 blaKPC-12). 4 EC contained blaKPC-3. KPC were from 7 countries, Italy had the highest number of KPC-producing isolates at 42 (56%). MVB inhibited 100% of KPC-producing isolates. Amikacin was the most active comparator against all ENT (94.2%S); colistin was the most active comparator against KPC-producing isolates (79.7%S). Conclusion These results demonstrate MVB has potent activity against ENT isolates from PHP including those producing KPC enzymes and suggest MVB is a useful treatment option for ICU and non-ICU PHP including VAP. Table 1 Disclosures Leonard R. Duncan, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Basilea Pharmaceutica International, Ltd. (Research Grant or Support)Dept of Health and Human Services (Research Grant or Support) Jennifer M. Streit, BS, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support) Mariana Castanheira, PhD, 1928 Diagnostics (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support)


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Elise Persyn ◽  
Mohamed Sassi ◽  
Marc Aubry ◽  
Martin Broly ◽  
Sandie Delanou ◽  
...  

2008 ◽  
Vol 52 (12) ◽  
pp. 4388-4399 ◽  
Author(s):  
Chris M. Pillar ◽  
Mohana K. Torres ◽  
Nina P. Brown ◽  
Dineshchandra Shah ◽  
Daniel F. Sahm

ABSTRACT Doripenem, a 1β-methylcarbapenem, is a broad-spectrum antibiotic approved for the treatment of complicated urinary tract and complicated intra-abdominal infections. An indication for hospital-acquired pneumonia including ventilator-associated pneumonia is pending. The current study examined the activity of doripenem against recent clinical isolates for the purposes of its ongoing clinical development and future longitudinal analysis. Doripenem and comparators were tested against 12,581 U.S. clinical isolates collected between 2005 and 2006 including isolates of Staphylococcus aureus, coagulase-negative staphylococci, Streptococcus pneumoniae, Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter spp. MICs (μg/ml) were established by broth microdilution. By MIC90, doripenem was comparable to imipenem and meropenem in activity against S. aureus (methicillin susceptible, 0.06; resistant, 8) and S. pneumoniae (penicillin susceptible, ≤0.015; resistant, 1). Against ceftazidime-susceptible Enterobacteriaceae, the MIC90 of doripenem (0.12) was comparable to that of meropenem (0.12) and superior to that of imipenem (2), though susceptibility of isolates exceeded 99% for all evaluated carbapenems. The activity of doripenem was not notably altered against ceftazidime-nonsusceptible or extended-spectrum β-lactamase screen-positive Enterobacteriaceae. Doripenem was the most potent carbapenem tested against P. aeruginosa (MIC90/% susceptibility [%S]: ceftazidime susceptible = 2/92%S, nonsusceptible = 16/61%S; imipenem susceptible = 1/98.5%S, nonsusceptible = 8/56%S). Against imipenem-susceptible Acinetobacter spp., doripenem (MIC90 = 2, 89.1%S) was twice as active by MIC90 as were imipenem and meropenem. Overall, doripenem potency was comparable to those of meropenem and imipenem against gram-positive cocci and doripenem was equal or superior in activity to meropenem and imipenem against Enterobacteriaceae, including β-lactam-nonsusceptible isolates. Doripenem was the most active carbapenem tested against P. aeruginosa regardless of β-lactam resistance.


2010 ◽  
Vol 31 (1) ◽  
pp. 47-53 ◽  
Author(s):  
Ebbing Lautenbach ◽  
Marie Synnestvedt ◽  
Mark G. Weiner ◽  
Warren B. Bilker ◽  
Lien Vo ◽  
...  

Background.Pseudomonas aeruginosa is one of the most common gram-negative hospital-acquired pathogens. Resistance of this organism to imipenem complicates treatment.Objective.To elucidate the risk factors for imipenem-resistant P. aeruginosa (IRPA) infection or colonization and to identify the effect of resistance on clinical and economic outcomes.Methods.Longitudinal trends in prevalence of IRPA from 2 centers were characterized during the period from 1989 through 2006. For P. aeruginosa isolates obtained during the period from 2001 through 2006, a case-control study was conducted to investigate the association between prior carbapenem use and IRPA infection or colonization, and a cohort study was performed to identify the effect of IRPA infection or colonization on mortality, length of stay after culture, and hospital cost after culture.Results.From 1989 through 2006, the proportion of P. aeruginosa isolates demonstrating resistance to imipenem increased from 13% to 20% (P< .001, trend). During the period from 2001 through 2006, there were 2,542 unique patients with P. aeruginosa isolates, and 253 (10.0%) had IRPA isolates. Prior carbapenem use was independently associated with IRPA infection or colonization (adjusted odds ratio [OR], 7.92 [95% confidence interval {CI}, 4.78-13.11]). Patients with an IRPA isolate recovered had higher in-hospital mortality than did patients with an imipenem-susceptible P. aeruginosa isolate (17.4% vs 13.4%; P = .01). IRPA infection or colonization was an independent risk factor for mortality among patients with isolates recovered from blood (adjusted OR, 5.43 [95% CI, 1.72-17.10]; P = .004) but not among patients with isolates recovered from other anatomic sites (adjusted OR, 0.78 [95% CI, 0.51-1.21]; P = .27). Isolation of IRPA was associated with longer hospital stay after culture (P<.001) and greater hospital cost after culture (P<.001) than was isolation of an imipenem-susceptible strain. In multivariable analysis, IRPA infection or colonization remained an independent risk factor for both longer hospital stay after culture (coefficient, 0.20 [95% CI, 0.04-0.36]; P = .02) and greater hospital cost after culture (coefficient, 0.30 [95% CI, 0.06-0.54]; P = .02).Conclusions.The prevalence of IRPA infection or colonization has increased significantly, with important implications for both clinical and economic outcomes. Interventions to curb this continued increase and strategies to optimize therapy are urgently needed.


2007 ◽  
Vol 51 (11) ◽  
pp. 4062-4070 ◽  
Author(s):  
B. Henrichfreise ◽  
I. Wiegand ◽  
W. Pfister ◽  
B. Wiedemann

ABSTRACT In this study, we analyzed the mechanisms of multiresistance for 22 clinical multiresistant and clonally different Pseudomonas aeruginosa strains from Germany. Twelve and 10 strains originated from cystic fibrosis (CF) and non-CF patients, respectively. Overproduction of the efflux systems MexAB-OprM, MexCD-OprJ, MexEF-OprN, and MexXY-OprM was studied. Furthermore, loss of OprD, alterations in type II topoisomerases, AmpC overproduction, and the presence of 25 acquired resistance determinants were investigated. The presence of a hypermutation phenotype was also taken into account. Besides modifications in GyrA (91%), the most frequent mechanisms of resistance were MexXY-OprM overproduction (82%), OprD loss (82%), and AmpC overproduction (73%). Clear differences between strains from CF and non-CF patients were found: numerous genes coding for aminoglycoside-modifying enzymes and located, partially in combination with β-lactamase genes, in class 1 integrons were found only in strains from non-CF patients. Furthermore, multiple modifications in type II topoisomerases conferring high quinolone resistance levels and overexpression of MexAB-OprM were exclusively detected in multiresistant strains from non-CF patients. Correlations of the detected phenotypes and resistance mechanisms revealed a great impact of efflux pump overproduction on multiresistance in P. aeruginosa. Confirming previous studies, we found that additional, unknown chromosomally mediated resistance mechanisms remain to be determined. In our study, 11 out of 12 strains and 3 out of 10 strains from CF patients and non-CF patients, respectively, were hypermutable. This extremely high proportion of mutator strains should be taken into consideration for the treatment of multiresistant P. aeruginosa.


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