In vivo development of antimicrobial resistance in Pseudomonas aeruginosa strains isolated from the lower respiratory tract of Intensive Care Unit patients with nosocomial pneumonia and receiving antipseudomonal therapy (original) (raw)
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Eurasian Journal of Pulmonology, 2016
Objective: Multidrug resistance is a major problem of Pseudomonas aeruginosa strains. We aimed to determine the level of resistance to the antipseudomonal antibiotics, the change in the rates of antibiotic resistance over the years, and mortality rate during hospital stay. Methods: The microbiology database of P. aeruginosa isolated from 3708 sputum and 485 bronchial lavage samples at Chest Diseases Public Hospital from January 2009 to December 2013 was retrospectively reviewed. Imipenem, amikacin, tobramycin, ciprofloxacin, piperacillin, piperacillin/tazobactam ceftazidime, and cefepime resistance rates of P. aeruginosa strains were determined. Antimicrobial susceptibility was determined by the disk diffusion method, according to the Clinical Laboratory Standards Institute (CLSI) guidelines. P. aeruginosa was defined as resistant (resistance to at least one of the antipseudomonal antibiotics), and multidrug resistant (MDR) (resistance to three or more drugs of following classes: β-lactam, carbapenem, aminoglycoside, and fluoroquinolone). Results: Five hundred and five P. aeruginosa isolates were tested. The antibiotic resistance rates were as follows; cefepime (26.7%), ceftazidime (23.2%), piperacillin (22.2%), imipenem (21.8%), piperacillin/tazobactam (19.2%), ciprofloxacin (17.4%), tobramycin (11.9%), and amikacin (7.3%). When compared 2009 and 2013, statistically significant reduction was observed in resistance rates to ciprofloxacin, amikacin, and cefepime antibiotics. Among 505 strains, 12.1% were designated as being MDR. Out of 505 patients investigated, 34 (6.7%) died during the hospital stay. Conclusion: The clinical significance of these findings is important in the selection of appropriate empirical treatment of serious P. aeruginosa infections.
Journal of Antimicrobial Chemotherapy, 2015
The main objective of this study was to investigate the relationship among the in vivo acquisition of antimicrobial resistance in Pseudomonas aeruginosa clinical isolates, the underlying molecular mechanisms and previous exposure to antipseudomonal agents. Methods: PFGE was used to study the molecular relatedness of the strains. The MICs of ceftazidime, cefepime, piperacillin/tazobactam, imipenem, meropenem, ciprofloxacin and amikacin were determined. Outer membrane protein profiles were assessed to study OprD expression. RT-PCR was performed to analyse ampC, mexB, mexD, mexF and mexY expression. The presence of mutations was analysed through DNA sequencing. Results: We collected 17 clonally related paired isolates [including first positive samples (A) and those with MICs increased ≥4-fold (B)]. Most B isolates with increased MICs of imipenem, meropenem and ceftazidime became resistant to these drugs. The most prevalent resistance mechanisms detected were OprD loss (65%), mexB overexpression (53%), ampC derepression (29%), quinolone target gene mutations (24%) and increased mexY expression (24%). Five (29%) B isolates developed multidrug resistance. Meropenem was the most frequently (71%) received treatment, explaining the high prevalence of oprD mutations and likely mexB overexpression. Previous exposure to ceftazidime showed a higher impact on selection of increased MICs than previous exposure to piperacillin/tazobactam. Conclusions: Stepwise acquisition of resistance has a critical impact on the resistance phenotypes of P. aeruginosa, leading to a complex scenario for finding effective antimicrobial regimens. In the clinical setting, meropenem seems to be the most frequent driver of multidrug resistance development, while piperacillin/tazobactam, in contrast to ceftazidime, seems to be the b-lactam least associated with the selection of resistance mechanisms.
Clinical microbiology, 2016
Pseudomonas aeruginosa (P. aeruginosa) has been reported as the most commonly isolated organisms in hospitals. The increasing resistance rate of P. aeruginosa to the common antimicrobial drugs has been reported worldwide. The present study aimed to investigate the incidence and antibiotic susceptibility pattern of P. aeruginosa from inpatients of two hospitals. Out of 1235 patient specimens, a total of 108 (8.7%) non-duplicated P. aeruginosa clinical isolates were identified, majority of them were from males (59.3%) and from patients above 60 years (31.5%). The most common incidence rate was from male ward (43.5%) followed by female ward (20.4%). Majority of P. aeruginosa strains were isolated from sputum specimen (38%) followed by urine specimen (14.8%). The results showed that 42.6% of the isolates were sensitive to all antibiotics while 36.1 % were found to be resistant to more than three antibiotics. The study showed that maximum antibiotic susceptibility rate of P. aeruginosa isolates was against amikacin (83.3%) followed by ciprofloxacin (75.9%). The maximum resistance rates among P. aeruginosa isolates were against Piperacillin/Tazobactum (38.5%,) followed by cefepime (32.4%). It was concluded that among P. aeruginosa isolates, amikacin was the most susceptible antimicrobial drug while piperacillin-tazobactam and cefipime were most resistant ones. Interventions and strategies to stop high resistance rate and optimizing therapy are needed.
Antibiotic utilization and Pseudomonas aeruginosa resistance in intensive care units
The new microbiologica, 2011
Pseudomonas aeruginosa is one of the most frequent and dangerous pathogens involved in the etiology of severe nosocomial infections. A retrospective observational study was conducted at all intensive care units of the University Hospital in Olomouc, Czech Republic (155 ICU beds). Complete antibiotic utilization data of the ICUs in the period of 1999 to 2008 were processed according to ATC/DDD system and expressed in defined daily doses per 100 bed-days (DBD). Utilization of meropenem, imipenem, ciprofloxacin, ofloxacin, pefloxacin, gentamicin, amikacin, ceftazidime, cefoperazone, cefoperazone/sulbactam and piperacillin/tazobactam was measured. Pseudomonas aeruginosa strains were isolated from clinical material obtained from patients hospitalized in ICUs. During the ten-year period, utilization of the entire group of antibiotics monitored grew. It increased from 23.52 DBD in 1999 to 27.48 DBD in 2008 with a peak of 33.04 DBD in 2007. P. aeruginosa accounted for as much as 42% of pneu...
Microbes and Infection, 2002
We investigated the epidemiology of antibiotic resistance and virulence properties among Pseudomonas aeruginosa clinical isolates collected in 1999 from patients hospitalized in the intensive care units of the centre hospitalier d'Orléans, in France. We compared the totality of the strains from mechanically ventilated patients with pneumonia (33 non-duplicate isolates, group 1) to 15 randomly chosen, imipenemresistant, extra-respiratory tract isolates, collected from non-infected patients hospitalized in the same units (group 2). The isolates were serotyped, typed by random amplified polymorphic DNA (RAPD), and screened for their pneumocyte cell adherence, cytotoxicity, and antibiotic resistance. A total of 35 RAPD profiles were found, and only two profiles were encountered in both groups, demonstrating a high genetic diversity. 84.8% of the group 1 and 93.3% of the group 2 isolates adhered to A549 cells. Three non-exclusive adhesive patterns were observed: a diffuse adhesion in 38 isolates, a localized adhesion in 14 isolates, and an aggregative adhesion in seven isolates. 78.8% of the group 1 and 93.3% of the group 2 isolates were cytotoxic. Considering all 48 isolates, there was a strong and statistically significant correlation between cytotoxicity and adherence. Among the three dominant serotypes, O:12 isolates were in majority avirulent, but the great majority of O:1 and all the O:11 isolates were found adherent and cytotoxic. Gentamicin was the least active antibiotic for both groups, and ceftazidime was the most active antibiotic for group 1 and amikacin for group 2. The penicillinase production phenotype was significantly correlated with a decrease in P. aeruginosa virulence.
Microbes and infection, 2002
We investigated the epidemiology of antibiotic resistance and virulence properties among Pseudomonas aeruginosa clinical isolates collected in 1999 from patients hospitalized in the intensive care units of the centre hospitalier d'Orléans, in France. We compared the totality of the strains from mechanically ventilated patients with pneumonia (33 non-duplicate isolates, group 1) to 15 randomly chosen, imipenemresistant, extra-respiratory tract isolates, collected from non-infected patients hospitalized in the same units (group 2). The isolates were serotyped, typed by random amplified polymorphic DNA (RAPD), and screened for their pneumocyte cell adherence, cytotoxicity, and antibiotic resistance. A total of 35 RAPD profiles were found, and only two profiles were encountered in both groups, demonstrating a high genetic diversity. 84.8% of the group 1 and 93.3% of the group 2 isolates adhered to A549 cells. Three non-exclusive adhesive patterns were observed: a diffuse adhesion in 38 isolates, a localized adhesion in 14 isolates, and an aggregative adhesion in seven isolates. 78.8% of the group 1 and 93.3% of the group 2 isolates were cytotoxic. Considering all 48 isolates, there was a strong and statistically significant correlation between cytotoxicity and adherence. Among the three dominant serotypes, O:12 isolates were in majority avirulent, but the great majority of O:1 and all the O:11 isolates were found adherent and cytotoxic. Gentamicin was the least active antibiotic for both groups, and ceftazidime was the most active antibiotic for group 1 and amikacin for group 2. The penicillinase production phenotype was significantly correlated with a decrease in P. aeruginosa virulence.
A total of 1,531 recent clinical isolates of Streptococcus pneumoniae were collected from 33 medical centers nationwide during the winter of 1999-2000 and characterized at a central laboratory. Of these isolates, 34.2% were penicillin nonsusceptible (MIC > 0.12 g/ml) and 21.5% were high-level resistant (MIC > 2 g/ml). MICs to all beta-lactam antimicrobials increased as penicillin MICs increased. Resistance rates among non-beta-lactam agents were the following: macrolides, 25.2 to 25.7%; clindamycin, 8.9%; tetracycline, 16.3%; chloramphenicol, 8.3%; and trimethoprim-sulfamethoxazole (TMP-SMX), 30.3%. Resistance to non-betalactam agents was higher among penicillin-resistant strains than penicillin-susceptible strains; 22.4% of S. pneumoniae were multiresistant. Resistance to vancomycin and quinupristin-dalfopristin was not detected. Resistance to rifampin was 0.1%. Testing of seven fluoroquinolones resulted in the following rank order of in vitro activity: gemifloxacin > sitafloxacin > moxifloxacin > gatifloxacin > levofloxacin ؍ ciprofloxacin > ofloxacin. For 1.4% of strains, ciprofloxacin MICs were >4 g/ml. The MIC 90 s (MICs at which 90% of isolates were inhibited) of two ketolides were 0.06 g/ml (ABT773) and 0.12 g/ml (telithromycin). The MIC 90 of linezolid was 2 g/ml. Overall, antimicrobial resistance was highest among middle ear fluid and sinus isolates of S. pneumoniae; lowest resistance rates were noted with isolates from cerebrospinal fluid and blood. Resistant isolates were most often recovered from children 0 to 5 years of age and from patients in the southeastern United States. This study represents a continuation of two previous national studies, one in 1994-1995 and the other in 1997-1998. Resistance rates with S. pneumoniae have increased markedly in the United States during the past 5 years. Increases in resistance from 1994-1995 to 1999-2000 for selected antimicrobial agents were as follows: penicillin, 10.6%; erythromycin, 16.1%; tetracycline, 9.0%; TMP-SMX, 9.1%; and chloramphenicol, 4.0%, the increase in multiresistance was 13.3%. Despite awareness and prevention efforts, antimicrobial resistance with S. pneumoniae continues to increase in the United States.
Clinical Microbiology and Infection, 2001
NCCLS agar dilution was used to test activity of telithromycin compared to clarithromycin, penicillin G, ciprofloxacin, levofloxacin, sparfloxacin and moxifloxacin against 26 pneumococci with defined quinolone resistance (type II topoisomerase and efflux) mechanisms. Thirteen strains were penicillin susceptible, six intermediate and seven resistant. Clarithromycin resistance (mef and/or erm) was seen in eight strains. Ciprofloxacin MICs (mg/L) were 8-64 compared to 1-32 (levofloxacin), 0.5 ! 32 (sparfloxacin) and 0.125-4 (moxifloxacin). Telithromycin MIC 50 and MIC 90 values (mg/L) were 0.016 and 0.25, with only one strain having an MIC of 2 mg/L.
Turkish Journal of Medical Sciences, 2005
The intensive care units (ICUs) are burdened with a high frequency of nosocomial infections often caused by multiresistant nosocomial pathogens. Pseudomonas aeruginosa has emerged as one of the most problematic Gram-negative pathogens. The objective of this study was to identify frequency of Pseudomonas aeruginosa from the various clinical samples in ICUs, and to investigate resistance patterns against various antibiotics widely used for treatment. This study was carried out between September 2000-September 2002. Antimicrobial susceptibility testing was performed by the disc diffusion method according to NCCLS (National Commitee for Clinical and Laboratory Standards) guidelines. The following antibiotics were tested: imipenem, meropenem, aztreonam, ciprofloxacin, ceftazidime, cefepime, piperacillin, norfloxacin and the aminoglycosides (gentamicin, netilmicin, tobramycin, and amikacin). Pseudomonas aeruginosa were isolated from 16.4 % (152/928) of the patients in ICUs. The highest Pseudomonas aeruginosa isolation was obtained in the burns unit (26.9%, 78/290) followed by, cardiovascular surgical ICU (17.6%, 13/74) general surgical ICU (24/164, 14.6 %), internal ICU (17/180, 9.4%) and coronary ICU (20/220, 9.1%). There is a statististically significant difference between surgical ICU and medical internal ICU (P < 0.05). The most effective antibiotics were carbapenems (imipenem and meropenem) and the resistance rates were detected as 15% and 20.4%, respectively among 152 Pseudomonas aeruginosa strains. In conclusion, the frequency of Pseudomonas aeruginosa was found to be high in patients treated at ICUs. The results demonstrate that the resistance rates are alarmingly high. To reduce the emergence and spread of antimicrobial-resistant pathogens in ICUs, monitoring and optimisation of antimicrobial use should be considered carefully. These findings suggest that the resistance rates of aminoglycosides, 3th generation antibiotics and quinolone are increasing progressively in Turkey.