BACKGROUND: Extensively drug-resistant (XDR) Pseudomonas aeruginosa and Acinetobacter baumannii are a threat to hospitalized patients. We evaluated the effects of antimicrobial combinations on XDR P. aeruginosa and A. baumannii isolates. METHODS: P. aeruginosa and A. baumannii isolates, which were resistant to all antibiotics except colistin (CL), were collected from eight hospitals in Korea. Genes encoding metallo-beta-lactamases (MBLs) and OXA carbapenemases were detected by PCR in eight P. aeruginosa and 30 A. baumannii isolates. In vitro synergy of antimicrobial combinations was tested by using the checkerboard method. RESULTS: Minimum inhibitory concentrations of beta-lactams, aminoglycosides, and fluoroquinolones were very high, while that of CL was low for majority of XDR P. aeruginosa and A. baumannii isolates. Antimicrobial combinations including Imipenem (IPM)-CL, ceftazidime (CAZ)-CL, and rifampin (RIF)-CL exerted only additive/indifferent effects on majority of XDR P. aeruginosa isolates. Proportions of XDR A. baumannii isolates that showed synergistic and additive/indifferent inhibition after treatment with antimicrobial combinations used are as follows: IPM-ampicillin-sulbactam (AMS), 17% and 80% isolates, respectively; IPM-rifampin (RIF), 13% and 81% isolates, respectively; IPM-CL, 13% and 87% isolates, respectively; and RIF-COL, 20% and 73% isolates, respectively. Significant proportion (19%) of XDR P. aeruginosa isolates produced MBLs, and majority (82%) of A. baumannii isolates produced either MBLs or OXA-23. CONCLUSIONS: Our results suggest that combinations of IPM-AMS, IPM-RIF, IPM-CL, and RIF-CL are more useful than individual drugs for treating 13-20% of XDR A. baumannii infections.
Acinetobacter baumannii/*drug effects/genetics/isolation & purification ; Aminoglycosides/pharmacology ; Anti-Infective Agents/*pharmacology ; Bacterial Proteins/genetics/metabolism ; Drug Resistance, Multiple, Bacterial/*drug effects ; Drug Synergism ; Fluoroquinolones/pharmacology ; Imipenem/pharmacology ; Microbial Sensitivity Tests ; Polymerase Chain Reaction ; Pseudomonas aeruginosa/*drug effects/genetics/isolation & purification ; beta-Lactamases/genetics/metabolism

BACKGROUND: Acinetobacter baumannii infections are difficult to treat owing to the emergence of various antibiotic resistant isolates. Because treatment options are limited for multidrug-resistant (MDR) A. baumannii infection, the discovery of new therapies, including combination therapy, is required. We evaluated the synergistic activity of colistin, doripenem, and tigecycline combinations against extensively drug-resistant (XDR) A. baumannii and MDR A. baumannii. METHODS: Time-kill assays were performed for 41 XDR and 28 MDR clinical isolates of A. baumannii by using colistin, doripenem, and tigecycline combinations. Concentrations representative of clinically achievable levels (colistin 2 microg/mL, doripenem 8 microg/mL) and achievable tissue levels (tigecycline 2 microg/mL) for each antibiotic were used in this study. RESULTS: The colistin-doripenem combination displayed the highest rate of synergy (53.6%) and bactericidal activity (75.4%) in 69 clinical isolates of A. baumannii. Among them, thedoripenem-tigecycline combination showed the lowest rate of synergy (14.5%) and bacteri-cidal activity (24.6%). The doripenem-tigecycline combination showed a higher antagonistic interaction (5.8%) compared with the colistin-tigecycline (1.4%) combination. No antagonism was observed for the colistin-doripenem combination. CONCLUSIONS: The colistin-doripenem combination is supported in vitro by the high rate of synergy and bactericidal activity and lack of antagonistic reaction in XDR and MDR A. baumannii. It seems to be necessary to perform synergy tests to determine the appropri-ate combination therapy considering the antagonistic reaction found in several isolates against the doripenem-tigecycline and colistin-tigecycline combinations. These findings should be further examined in clinical studies.
Acinetobacter Infections/drug therapy/microbiology ; Acinetobacter baumannii/*drug effects/genetics/isolation & purification ; Anti-Bacterial Agents/*pharmacology/therapeutic use ; Bacterial Proteins/genetics ; Carbapenems/*pharmacology/therapeutic use ; Colistin/*pharmacology/therapeutic use ; Drug Resistance, Multiple, Bacterial/*drug effects ; Drug Synergism ; Drug Therapy, Combination ; Humans ; Microbial Sensitivity Tests ; Minocycline/*analogs & derivatives/pharmacology/therapeutic use ; Multilocus Sequence Typing ; beta-Lactamases/genetics

BACKGROUND: We investigated the whole genome sequence (WGS) of a carbapenem-resistant Acinetobacter baumannii isolate belonging to the global clone 2 (GC2) and predicted resistance islands using a software tool. METHODS: A. baumannii strain YU-R612 was isolated from the sputum of a 61-yr-old man with sepsis. The WGS of the YU-R612 strain was obtained by using the PacBio RS II Sequencing System (Pacific Biosciences Inc., USA). Antimicrobial resistance genes and resistance islands were analyzed by using ResFinder and Genomic Island Prediction software (GIPSy), respectively. RESULTS: The YU-R612 genome consisted of a circular chromosome (ca. 4,075 kb) and two plasmids (ca. 74 kb and 5 kb). Its sequence type (ST) under the Oxford scheme was ST191, consistent with assignment to GC2. ResFinder analysis showed that YU-R612 possessed the following resistance genes: four β-lactamase genes bla(ADC-30), bla(OXA-66), bla(OXA-23), and bla(TEM-1); armA, aadA1, and aacA4 as aminoglycoside resistance-encoding genes; aac(6')Ib-cr for fluoroquinolone resistance; msr(E) for macrolide, lincosamide, and streptogramin B resistance; catB8 for phenicol resistance; and sul1 for sulfonamide resistance. By GIPSy analysis, six putative resistant islands (PRIs) were determined on the YU-R612 chromosome. Among them, PRI1 possessed two copies of Tn2009 carrying bla(OXA-23), and PRI5 carried two copies of a class I integron carrying sul1 and armA genes. CONCLUSIONS: By prediction of resistance islands in the carbapenem-resistant A. baumannii YU-R612 GC2 strain isolated in Korea, PRIs were detected on the chromosome that possessed Tn2009 and class I integrons. The prediction of resistance islands using software tools was useful for analysis of the WGS.
Acinetobacter Infections/*drug therapy/microbiology ; Acinetobacter baumannii/drug effects/*genetics/isolation & purification ; Anti-Bacterial Agents/pharmacology/*therapeutic use ; Bacterial Proteins/genetics ; Carbapenems/*therapeutic use ; DNA, Bacterial/chemistry/*genetics/metabolism ; Drug Resistance, Bacterial ; Genomic Islands/genetics ; Humans ; Microbial Sensitivity Tests ; Multilocus Sequence Typing ; Plasmids/genetics/metabolism ; Polymerase Chain Reaction ; Sequence Analysis, DNA

BACKGROUND/AIMS: Nosocomial infections caused by multidrug-resistant (MDR) Acinetobacter baumannii have become public-health problem. However, few studies have evaluated the control of endemic MDR A. baumannii in Intensive Care Units (ICUs). Therefore, we investigated the effectiveness of antimicrobial stewardship and comprehensive intensified infection control measures for controlling endemic MDR A. baumannii in ICUs at a tertiary care center. METHODS: Carbapenem use was strictly restricted through antimicrobial stewardship. Environmental cleaning and disinfection was performed at least 3 times per day in addition to basic infection control measures. Isolation using plastic curtains and contact precautions were applied to patients who were colonized or infected with MDR A. baumannii. The outcome was measured as the incidence density rate of hospital-onset MDR A. baumannii among patients in the ICUs. RESULTS: The incidence density rate of hospital-onset MDR A. baumannii decreased from 22.82 cases per 1,000 patient-days to 2.68 cases per 1,000 patient-days after the interventions were implemented (odds ratio, 0.12; 95% confidence interval, 0.03 to 0.4; p < 0.001). The mean monthly use of carbapenems also decreased from 134.99 +/- 82.26 defined daily doses per 1,000 patient-days to 94.85 +/- 50.98 defined daily doses per 1,000 patient-days (p = 0.016). CONCLUSIONS: Concomitant implementation of strict antimicrobial stewardship and comprehensive infection control measures effectively controlled endemic MDR A. baumannii in our ICUs within 1 year.
Acinetobacter Infections/epidemiology/microbiology/*prevention & control/transmission ; Acinetobacter baumannii/*drug effects/pathogenicity ; Anti-Bacterial Agents/adverse effects/*therapeutic use ; Carbapenems/adverse effects/*therapeutic use ; Chi-Square Distribution ; Cross Infection/epidemiology/microbiology/*prevention & control/transmission ; Disinfection ; *Drug Resistance, Multiple, Bacterial ; *Endemic Diseases ; Hand Disinfection ; Humans ; Incidence ; Infection Control/*methods ; Microbial Sensitivity Tests ; Odds Ratio ; Patient Isolation ; Program Evaluation ; Republic of Korea/epidemiology ; Risk Factors ; Tertiary Care Centers ; Time Factors ; Treatment Outcome

PURPOSE: Colistin resistance in Acinetobacter baumannii (A. baumannii) is mediated by a complete loss of lipopolysaccharide production via mutations in lpxA, lpxC, and lpxD gene or lipid A modifications via mutations in the pmrA and pmrB genes. However, the exact mechanism of therapy-induced colistin resistance in A. baumannii is not well understood. MATERIALS AND METHODS: We investigated the genotypic and phenotypic changes that underlie pan-drug resistance mechanisms by determining differences between the alterations in extensively drug-resistant (XDR) A. baumannii (AB001 and AB002) isolates and a pan-drug resistant (PDR) counterpart (AB003) recovered from one patient before and after antibiotic treatment, respectively. RESULTS: All three clinical isolates shared an identical sequence type (ST138), belonging to the global epidemic clone, clonal complex 92, and all produced OXA-23 carbapenemase. The PDR AB003 showed two genetic differences, acquisition of armA gene and an amino acid substitution (Glu229Asp) in pmrB gene, relative to XDR isolates. No mutations were detected in the pmrA, pmrC, lpxA, lpxC, or lpxD genes in all three isolates. In matrix-assisted laser desorption ionization-time of flight analysis, the three isolates commonly showed two major peaks at 1728 m/z and 1912 m/z, but peaks at 2034 m/z, 2157 m/z, 2261 m/z, and 2384 m/z were detected only in the PDR A. baumannii AB003 isolate. CONCLUSION: Our results show that changes in lipid A structure via a mutation in the pmrB gene and acquisition of armA gene might confer resistance to colistin and aminoglycosides to XDR A. baumannii strains, resulting in appearance of a PDR A. baumannii strain of ST138.
Acinetobacter Infections/*drug therapy/microbiology ; Acinetobacter baumannii/*drug effects/*genetics/isolation & purification ; Aged ; Anti-Bacterial Agents/*pharmacology/therapeutic use ; Bacterial Proteins/*genetics ; Colistin/*pharmacology/therapeutic use ; *Drug Resistance, Bacterial ; Electrophoresis, Gel, Pulsed-Field ; Genotype ; Humans ; Male ; Microbial Sensitivity Tests ; Molecular Typing ; Mutation ; Polymerase Chain Reaction ; Transcription Factors ; beta-Lactamases

OBJECTIVETo study the drug resistance of Acinetobacter baumannii (AB) producing VIM-2-type metallo-β-lactamase (MBL) isolated from burn patients of our ward against carbapenem antibiotics and its homology.

METHODSA total of 400 strains of AB (identified) were isolated from sputum, urine, blood, pus, and wound drainage. of burn patients hospitalized in our ward from September 2011 to March 2014. Drug resistance of the 400 strains of AB to 15 antibiotics, including compound sulfamothoxazole, aztreonam, etc. , was tested using the automatic microorganism identifying and drug sensitivity analyzer. Among the carbapenems-resistant AB isolates, modified Hodge test was applied to screen carbapenemase-producing strains. The carbapenemase genes of the carbapenemase-producing strains, and the mobile genetic elements class I-integron (Intl1) gene and conserved sequence (CS) of carbapenemase-producing strains carrying blaVIM-2 gene were determined with PCR and DNA sequencing. For carbapenemase-producing strains carrying blaVIM-2 gene, synergism test with imipenem-ethylene diamine tetraacetic acid (EDTA) and enhancement test with imipenem-EDTA and ceftazidime-EDTA were used to verify the MBL-producing status. Drug resistance of the VIM-2-type MBL-producing AB strains was analyzed. For VIM-2-type MBL-producing AB strains, plasmid conjugation experiment was used to explore the transfer of plasmid; outer membrane protein (OMP) CarO gene was detected by PCR. For VIM-2-type MBL-producing AB strains carrying CarO gene, the protein content of CarO was analyzed with sodium dodecyl sulfate polyacrylamide gel electro- phoresis. The repetitive consensus sequence of Enterobacteriaceae genome PCR (ERIC-PCR) was carried out for gene typing of VIM-2-type MBL-producing AB strains to analyze their homology.

RESULTS(1) The resistant rates of the 400 strains of AB against levofloxacin and compound sulfamethoxazole were low. A total of 381 carbapenems-resistant AB strains were screened, including 240 carbepenemase-producing strains. (2) Out of the 240 carbepenemase-producing strains, 18 strains were found to harbor the blaVIM-2 gene, accounting for 7.5%; 133 strains carried the blaTEM-1 gene, accounting for 55.42%; 195 strains carried the blaOXA23 gene, accounting for 81.25%; 188 strains carried the bla(armA) gene, accounting for 78.33%. (3) Eighteen carbepenemase-producing strains which carried the bla(VIM-2) gene were found to carry the Intl1 gene, showing the Intl1-VIM linkage. Simultaneously, Intl1 variable area CS showed diversity. (4) Eighteen carbepenemase-producing strains which carried the blaVIM-2 gene were verified to produce MBL. The resistant rates of the 18 strains of AB against compound sulfamethoxazole were the lowest, followed by levofloxacin and cefoperazone/sulbactam, and those against the other antibiotics were above 60.00%. (5) Through multiple joint tests, plasmid conjugation experiment positive transfer strain was not found in 18 VIM-2-type MBL-producing AB strains. (6) Nine out of the 18 VIM-2-type MBL-producing AB strains were found to carry CarO gene. The OMP CarO of VIM-2-type MBL-producing AB strains carrying CarO gene was lost or lowered in the protein content. (7) The 18 VIM-2-type MBL-producing AB strains were classified into 6 genotypes by the ERIC-PCR. There were respectively 6, 4, 3, and 1 stain (s) in genotypes A, B, C, and F, and there were 2 strains in genotypes D and E respectively.

CONCLUSIONSThe resistance mechanism of AB against carbapenems is mainly mediated by blaTEM-1, blaOXA-23, and bla(arma); meanwhile, VIM-2-type MBL-producing and lack or change in OMP CarO are attributable to carbapenems resistance of clinically isolated AB from burn wards, and the Intl1 gene may take a part in blaVIM-2 gene transmission.

Acinetobacter baumannii ; drug effects ; enzymology ; genetics ; isolation & purification ; Anti-Bacterial Agents ; pharmacology ; therapeutic use ; Bacterial Proteins ; Burns ; drug therapy ; microbiology ; Carbapenems ; pharmacology ; Drug Resistance, Bacterial ; Genes, Bacterial ; Humans ; Imipenem ; pharmacology ; Microbial Sensitivity Tests ; Sulbactam ; pharmacology ; beta-Lactamases ; genetics

OBJECTIVETo analyze the detection, drug resistance, and status of infection of Acinetobacter baumannii (AB) in burn ICU during 3 years.

METHODSA total of 2 010 specimens of wound secretion, blood, venous catheter attachment, sputum, stool and urine were collected from 505 burn patients hospitalized in our burn ICU from January 2011 to December 2013, and bacterial culture was performed. Pathogens were identified by automatic microorganism identifying and drug sensitivity analyzer. Drug resistance of all the obtained AB to 16 antibiotics commonly used in clinic, including cefoperazone/sulbactam, polymyxin, etc., was tested with K-B paper disk diffusion method. Patients with AB infection were ascertained. The WHONET 5.6 software was used to analyze the distribution of pathogens during 3 years, the isolation of AB with different sources and the status of drug resistance of AB to 16 antibiotics each year, and the status of patients with AB infection, and their outcome.

RESULTSA total of 961 strains of pathogens were isolated, among which 185 (19.25%) strains were Gram positive cocci, 728 (75.75%) strains were Gram negative bacilli, and 48 (4.99%) strains were fungi. A total of 172 strains of AB were isolated, ranking the second place among all the detected pathogens, with 67 (38.95%) strains from wound secretion, 11 (6.40%) strains from blood, 23 (13.37%) strains from venous catheter attachment, and 71 (41.28%) strains from sputum, no AB strain was isolated from feces or urine. The AB strains were found sensitive to polymyxin and with relatively low drug resistance rate to minocycline, while the drug resistance rates were over 80.0% to the other 14 antibiotics commonly used in clinic in 2013. AB culture of wound secretion was positive in 27 patients. Among them, 7 patients suffered from wound infection, and the wound infection was caused by AB in 1 out of the 7 patients. AB culture of blood was positive in 7 patients. Among them, 3 patients suffered from bloodstream infection, and the infection was due to AB invasion in 1 out of the 3 patients. AB culture of venous catheter attachment was positive in 20 patients. Among them, 8 patients suffered from bloodstream infection, and the infection was due to AB invasion in 1 out of the 8 patients. AB culture of sputum was positive in 35 patients. Among them, 13 patients suffered from ventilatory associated pneumonia, and 2 out of the 13 patients were diagnosed as AB infection. A total of 69 patients were AB culture positive, among them 64 patients were cured, 2 patients were transferred to other hospitals, and 3 patients died, with the mortality rate of 4.35%.

CONCLUSIONSAB in our burn ICU has a high detection rate and extensive drug resistance in above-mentioned 3 years. However, AB was mainly colonized in patients with extensive burns with a low mortality rate.

Acinetobacter Infections ; drug therapy ; epidemiology ; microbiology ; Acinetobacter baumannii ; drug effects ; isolation & purification ; Anti-Bacterial Agents ; pharmacology ; Burns ; microbiology ; Cross Infection ; Drug Resistance ; Gram-Negative Bacteria ; isolation & purification ; Humans ; Intensive Care Units ; Microbial Sensitivity Tests

BACKGROUND: Multidrug-resistant (MDR) Acinetobacter spp. acquire antimicrobial agent-resistance genes via class 1 integrons. In this study, integrons were characterized to investigate the antimicrobial resistance mechanisms of MDR Acinetobacter isolates. In addition, the relationship between the integron type and integron-harboring bacterial species was analyzed by using epidemiological typing methods. METHODS: Fifty-six MDR Acinetobacter spp.-A. baumannii (N=30), A. bereziniae (N=4), A. nosocomialis (N=5), and A. pittii (N=17)-were isolated. The minimum inhibitory concentrations (MICs) were determined on the basis of the results of the Epsilometer test (Etest). PCR and DNA sequencing was performed to characterize the gene cassette arrays of class 1 integrons. Multilocus sequence typing (MLST) and repetitive extragenic palindromic sequence (REP)-PCR were performed for epidemiological typing. RESULTS: Class 1 integrons were detected in 50 (89.3%) of the 56 isolates, but no class 2 or 3 integron was found within the cohorts. The class 1 integrons were classified into 4 types: 2.3-kb type A (aacA4-catB8-aadA1), 3.0-kb type B (aacA4-blaI(MP-1)-bla(OXA-2)), 3.0-kb type C (bla(VIM-2)-aacA7-aadA1), and 1.8-kb type D (aac3-1-bla(OXA-2)-orfD). Type A was most prevalent and was detected only in A. baumannii isolates, except for one A. bereziniae isolate; however, type B was amplified in all Acinetobacter isolates except for A. baumannii isolates, regardless of clone and separation time of the bacteria. CONCLUSIONS: Although class 1 integron can be transferred horizontally between unrelated isolates belonging to different species, certain types of class 1 integrons tend to transfer horizontally and vertically among A. baumannii or non-baumannii Acinetobacter isolates.
Acinetobacter/drug effects/isolation & purification/*metabolism ; Acinetobacter Infections/epidemiology/microbiology ; Acinetobacter baumannii/drug effects/isolation & purification/metabolism ; Anti-Bacterial Agents/pharmacology ; DNA, Bacterial/chemistry/metabolism ; Drug Resistance, Multiple, Bacterial ; Humans ; Integrons/*genetics ; Microbial Sensitivity Tests ; Multilocus Sequence Typing ; Polymerase Chain Reaction ; Republic of Korea

BACKGROUND: Acinetobacter baumannii is one of the most important pathogens capable of colonization in burn patients, leading to drug-resistant wound infections. This study evaluated the distribution of the AdeABC efflux system genes and their relationship to ciprofloxacin resistance in A. baumannii isolates collected from burn patients. METHODS: A total of 68 A. baumannii clinical strains were isolated from patients hospitalized in Motahari Burns Center in Tehran, Iran. Ciprofloxacin susceptibility was tested by the disk diffusion and agar dilution methods. PCR amplification of the adeRS-adeB drug efflux genes was performed for all resistant and susceptible isolates. To assess the role of the drug efflux pump in ciprofloxacin susceptibility, carbonyl cyanide 3-chlorophenylhydrazone (CCCP) was used as an efflux pump inhibitor (EPI). RESULTS: Approximately 95.6% of the Acinetobacter isolates were resistant to ciprofloxacin, with minimum inhibitory concentration (MIC) values ranging from 4 to > or =128 microg/mL. The susceptibility of 86.1% of the resistant isolates increased by factors of 2 to 64 in the presence of CCCP. All resistant isolates were positive for the adeRS-adeB genes, and 73.2% of them had mutations in the AdeRS regulatory system. CONCLUSIONS: The results showed that AdeABC genes are common in A. baumannii, which might be associated with ciprofloxacin non-susceptibility, as indicated by the observed linkage to the presence of the genes essential for the activity of the AdeABC, several single mutations occurring in the adeRS regulatory system, and an increase of ciprofloxacin susceptibility in the presence of a CCCP EPI.
ATP-Binding Cassette Transporters/antagonists & inhibitors/genetics/*metabolism ; Acinetobacter Infections/diagnosis/microbiology ; Acinetobacter baumannii/*drug effects/genetics/isolation & purification ; Anti-Bacterial Agents/*pharmacology ; Bacterial Proteins/antagonists & inhibitors/genetics/*metabolism ; Base Sequence ; Ciprofloxacin/*pharmacology ; DNA, Bacterial/chemistry/genetics/metabolism ; Drug Resistance, Bacterial ; Humans ; Hydrazones/pharmacology ; Microbial Sensitivity Tests ; Mutation ; Polymerase Chain Reaction

OBJECTIVETo investigate the mechanism of drug resistance of carbapenems-resistant Acinetobacter baumannii (CRAB) in burn patients and the antimicrobial activity of a combination of drugs against this bacteria in vitro.

METHODSA total of 135 strains of Acinetobacter baumannii (AB) from wound excretion, sputum, and venous catheter wall of patients hospitalized in our department from January 2011 to July 2013 were collected individually. Drug resistance of 135 strains of AB to 12 antibiotics commonly-used in clinic was detected using K-B paper diffusion method. Among the CRAB strains, double-disk synergy test was used to screen metallo-β-lactamase (MBL)-producing strains, and the drug resistance rates between MBL-producing strains and non-MBL-producing strains were compared. Minimal inhibitory concentration (MIC), 50% MIC (MIC50), and 90% MIC (MIC90) of cefoperazone/sulbactam, imipenem, cefepime, ampicillin/sulbactam, and amikacin used alone against MBL-producing CRAB were determined by broth microdilution method. MIC, MIC50, and MIC90 of amikacin respectively combined with imipenem, cefoperazone/sulbactam, cefepime, or ampicillin/sulbactam against MBL-producing CRAB were determined by checkerboard method with diluted agar. Fractional inhibitory concentration (FIC) index was calculated to determine the antibacterial effect of each combination of two antibiotics. Synergy with FIC lower than or equal to 0.5, or additivity with FIC higher than 0.5 and lower than or equal to 1.0 was regarded as effective, and indifference with FIC higher than 1.0 and lower than or equal to 2.0 or antagonism with FIC higher than 2.0 was regarded as ineffective. The effective rate was calculated. Data were processed with Chi-square test.

RESULTSThe resistant rates of the 135 strains of AB to imipenem, meropenem, and ceftazidime were high, and those of piperacillin/tazobactam and ampicillin/sulbactam were low. A total of 120 strains of CRAB was screened, accounting for 88.89%, among which the MBL-producing strains accounted for 78.33% (94/120). The resistant rates of MBL-producing strains to piperacillin/tazobactam, imipenem, meropenem, piperacillin, and cefepime were respectively 59.5%, 87.2%, 93.5%, 87.0%, 86.0%, and they were significantly higher than those of non-MBL-producing strains (respectively 43.0%, 81.3%, 87.5%, 78.4%, 64.0%, with χ(2) values from 4.571 to 8.260, P < 0.05 or P < 0.01). Among the inhibition concentrations of each of the 5 antibiotics used alone against MBL-producing strains, MIC, MIC50, and MIC90 of ampicillin/sulbactam were the lowest, respectively 4.00, 16, 64 µg/mL, while those of cefepime were high, respectively 32.00, 128, 512 µg/mL. MIC, MIC50, and MIC90 of amikacin combined with each of the other 4 antibiotics were decreased from 50.00% to 98.44% as compared with that of single administration of each antibiotic. Among the 94 strains of MBL-producing CRAB, the synergic, additive, indifferent, and antagonistic effects were respectively observed in 40, 33, 6, and 15 strains applied with combination of amikacin and ampicillin/sulbactam; 42, 30, 5, 17 strains applied with combination of amikacin and cefoperazone/sulbactam; 38, 15, 19, 22 strains applied with combination of amikacin and cefepime; 34, 2, 37, 21 strains applied with combination of amikacin and imipenem, among which the antibacterial effective rates decreased successively, respectively 77.7%, 76.6%, 56.4%, and 38.3%. The former two rates were respectively significantly higher than the latter two rates (with χ(2) values from 8.618 to 29.889, P values below 0.01).

CONCLUSIONSProduction of MBL is the main mechanism of resistance of the CRAB isolated from burn patients hospitalized in our department against carbapenems in about 3 years. The antibacterial effects of amikacin combined with each of the former-mentioned 4 agents are better than those of each of the five antibiotics used singly, and the effects are particularly obvious when combining amikacin with compound agent containing enzyme inhibitors.

Acinetobacter Infections ; drug therapy ; microbiology ; Acinetobacter baumannii ; drug effects ; isolation & purification ; Ampicillin ; pharmacology ; Anti-Bacterial Agents ; pharmacology ; Carbapenems ; pharmacology ; Cephalosporins ; pharmacology ; Drug Resistance ; Humans ; In Vitro Techniques ; Microbial Sensitivity Tests ; Penicillanic Acid ; analogs & derivatives ; pharmacology ; Pharmaceutical Preparations ; Piperacillin ; pharmacology ; Sulbactam ; pharmacology ; Thienamycins ; pharmacology ; beta-Lactamase Inhibitors ; pharmacology