Imipenem-Resistant Pseudomonas Aeruginosa As Nosocomial Pathogen: Epidemiological Survey And Resistant Mechanism

Objective1. To investigate the nosocomial infection status and the drug resistance of imipenem-resistant Pseudomonas aeruginosa to instruct clinical application of antibiotics.2. To explore the risk factors for nosocomial infection caused by imipenem-resistant Pseudomonas aeruginosa(IRPA) or imipenem-susceptive Pseudomonas aeruginosa(ISPA) to provide reference for reducing and controlling this kind of nosocomial infection.3. To study on the relationship between the active efflux pump system and imipenem resistance to clarify the molecular mechanism of imipenem resistance among Pseudomonas aeruginosa.Methods1. The case patients who were infected by imipenem-resistant Pseudomonas aeruginosa were investigated by a statistics designed according to some reference. The drug resistance spectrum and the trend of resistant rate of imipenem-resistant Pseudomonas aeruginosa. Then 840 strains, including 145 isolates resistant to imipenem, were investigated.2. A case-control study design was used for the comparison of 2 groups of case patients with control patients. The first group of case patients had nosocomial isolation of imipenem-resistant Pseudomonas aeruginosa, and the second group had imipenem-susceptible Pseudomonas. aeruginosa. Control patients were selected from the same medical or surgical services from which case patients were receiving care when isolation of IRPA or 1SPA occurred. Risk factors analyzed included antimicrobials used, comorbid conditions, and demographic variables. IRPA was recovered from 67 patients, and ISPA from 150 patients, the control case were 200 and 159 respectively. All patients were from Renmin Hospital of Wuhan University during Jan 2002 to Dec 2003.Data were analyzed with unconditional logistic regression and principle component analysis.3. 108 Pseudomonas aeruginosa isolated from 2002 to 2003 were identified by VITEK 32 system. Minimal inhibitory concentrations (MIC) was tested. According to the result of MIC, the isolates was divided into two groups, resistantand susceptive. Then, the level of mRNA expressions of OprM in clinical Pseudomonas aeruginosa isolates was determined by reverse translation polymerase chain reaction (RT-PCR). Results1. There were 145 imipenem-resistant Pseudomonas aeruginosa among 840 isolates from the patients stayed in hospital during January 2001 to June 2OO4.The average isolated rate was 17.3%, and it had a trend of ascending year after year.2. These strains were mostly isolated from sputum specimen (50.3%) and wound secretion specimen (28.3%), and mostly came from department of ICU, respiratory diseases and neurosurgery.3. According to the result of MIC, we knew that there were different susceptivity of SMZ, gentamicin, ciprofloxacin, piperacillin, amikacin, cefotaxime, aztreonam, except for chloramphenicol between imipenem-resistant isolates and imipenem-susceptive isolates. And the drug resistant rates of the former were higher than that of the latter(p<0.05).4. The imipenem-resistant strains had some susceptivity to meropenem, and the susceptive rate was 74.5%, but contrarily it was only 5.1%.5. To treat the imipenem-resistant Pseudomonas aeruginosa nosocomial infection, there were more than two kinds of antibiotics used in the same time.6. Multivariate unconditional logistic regression analysis showed that the independent risk factors for IRPA nosocomial infection were time at risk (OR, 1.03; 95%CI, 1.01-1.04), imipenem (OR, 4.65; 95%CI, 1.35-11.52), PIP/TAZ (OR, 3.37; 95%CI, 1.85-9.43) and quinolones (OR, 1.85; 95%CI, 1.25-5.34); the third cephalosporins (OR, 2.54; 95%CI, 1.26-5.23) and aminoglycoside antibiotics (OR, 1.86; 95%C1, 1.42-3.26), time at risk (OR, 1.05; 95%CI, 1.03-1.05) were associated with isolated 1SPA?7. The mRNA level of the outer membrane protein OprM in Pseudomonas aeruginosa including imipenem-resistant isolates and susceptive isolates were detected respectively. We found that all of the isolates had the outer membrane protein OprM and the levels of mRNA expression of OprM in imipenem-resistant stains were higher than those in susceptible stains (p<0.05).Conclusions1. The isolated rate of IRPA ascends year after year, and it is a focus that we should pay more attention to. According to the investigation result in our hospital, theIRPA nosocomial infection is mostly happened in the department of ICU, respiratory diseases and neurosurgery.2. IRPA show multi-drug resistance to most common used antibiotics. So, it is very difficult to deal with it. Amikacin is a choice in experiential use.3. Nosocomial infection caused by IRPA could attribute to using imipenem and other antibiotics, such as PIP/TAZ, quinolones, so limiting the use of imipenem alone may not be sufficient to contain the increasing incidence if IRPA.4. The level of mRNA expression of OprM in Pseudomonas aeruginosa isolates is related with imipenem-resistance, and the high imipenem resistance of Pseudomonas aeruginosa is generated from the interplay among the active system and other mechanism.