Acinetobacter baumannii is undoubtedly one of the most successful pathogens responsible for hospital-acquired nosocomial infections in the modern healthcare system. Due to the prevalence of infections and outbreaks caused by multi-drug resistant A. baumannii, few antibiotics are effective for treating infections caused by this pathogen. To overcome this problem, knowledge of the pathogenesis and antibiotic resistance mechanisms of A. baumannii is important. In this review, we summarize current studies on the virulence factors that contribute to A. baumannii pathogenesis, including porins, capsular polysaccharides, lipopolysaccharides, phospholipases, outer membrane vesicles, metal acquisition systems, and protein secretion systems. Mechanisms of antibiotic resistance of this organism, including acquirement of β-lactamases, up-regulation of multidrug efflux pumps, modification of aminoglycosides, permeability defects, and alteration of target sites, are also discussed. Lastly, novel prospective treatment options for infections caused by multi-drug resistant A. baumannii are summarized.

Metallo-β-lactamase-producing Pseudomonas aeruginosa (MPPA) is an important nosocomial pathogen that shows resistance to all β-lactam antibiotics except monobactams. There are various types of metallo-β-lactamases (MBLs) in carbapenem-resistant P. aeruginosa including Imipenemase (IMP), Verona integron-encoded metallo-β-lactamase (VIM), Sao Paulo metallo-β-lactamase (SPM), Germany imipenemase (GIM), New Delhi metallo-β-lactamase (NDM), Florence imipenemase (FIM). Each MBL gene is located on specific genetic elements including integrons, transposons, plasmids, or on the chromosome, in which they carry genes encoding determinants of resistance to carbapenems and other antibiotics, conferring multidrug resistance to P. aeruginosa. In addition, these genetic elements are transferable to other Gram-negative species, increasing the antimicrobial resistance rate and complicating the treatment of infected patients. Therefore, it is essential to understand the epidemiology, resistance mechanism, and molecular characteristics of MPPA for infection control and prevention of a possible global health crisis. Here, we highlight the characteristics of MPPA.

We investigated an outbreak of Acinetobacter baumannii in an intensive care unit and in the surgery, medicine, neurology, and urology wards of the Kosin University Gospel Hospital in Busan, Korea. The outbreak involved 36 cases of infection by A. baumannii producing the OXA-23 ␤-lactamase over an 8-month period and was caused by a single pulsed-field gel electrophoresis clone. The epidemic isolates were characterized by a modified cloverleaf synergy test. Isoelectric focusing of crude bacterial extracts detected one nitrocefin-positive band with a pI value of 6.65. PCR amplification and characterization of the amplicons by direct sequencing indicated that the epidemic isolates carried a bla OXA-23 determinant. The epidemic isolates were characterized by a multidrug resistance phenotype that remained unchanged over the outbreak, including penicillins, cephamycins, extended-spectrum cephalosporins, carbapenems, monobactams, and aminoglycosides. This study shows that the bla OXA-23 resistance determinant may become an emerging therapeutic problem.Acinetobacter baumannii has emerged as an important nosocomial pathogen in outbreaks of hospital infections and is ranked second after Pseudomonas aeruginosa among nosocomial pathogens of aerobic nonfermentative gram-negative bacilli (17,19). A. baumannii causes respiratory and urinary tract infections, meningitis, endocarditis, burn infections, and wound sepsis, especially in intensive care units (ICUs) (4). A. baumannii infections are often difficult to eradicate due to high-level resistance to many antibiotics as a result of both intrinsic and acquired mechanisms. ␤-Lactamase production is the most important mechanism of acquired ␤-lactam resistance in gram-negative pathogens (21). Carbapenems (e.g., imipenem and meropenem) have become the drugs of choice against Acinetobacter infections in many centers but are being compromised by the emergence of carbapenem-hydrolyzing ␤-lactamase (carbapenemase) of molecular classes B and D (14). Class B carbapenemases found thus far in Acinetobacter spp. include various IMP-and VIM-type metallo-␤-lactamases (http: //www.lahey.org/studies/webt.asp), but most Acinetobacter spp. produce zinc-independent members of ␤-lactamase molecular class D (1). Sequenced carbapenemases of this latter class from that species include the following two distinct clusters: (i) the OXA-23-like cluster (OXA-23 and -27) and (ii) the OXA-24-like cluster . OXA-23 and OXA-27 have 99% amino acid identity, whereas they have only 60% identity with those of OXA-24-like cluster (1,3,6,7).Over an 8-month period from January to August 2003, 193 A. baumannii isolates were isolated from 193 patients hospitalized at the Kosin University Gospel Hospital. The purpose of the present study was to investigate an outbreak of A. baumannii in Korea and to characterize the imipenem resistance mechanism of the outbreak isolates. MATERIALS AND METHODS Bacterial strains and susceptibility tests. A total of 193 nonrepetitive clinical isolates of A. baumannii were isolated from Ja...

CTX-M-type and/or SHV-12 ESBL-producing E. coli and K. pneumoniae isolates are spreading, and a GES-type ESBL has emerged in Korea.

To determine the prevalence and genotypes of extended-spectrum beta-lactamases (ESBLs) among clinical isolates of Klebsiella pneumoniae and Escherichia coli, we performed antibiotic susceptibility testing, pI determination, induction testing, transconjugation, and DNA sequencing analysis. Among the 509 isolates collected from 13 university hospitals in Korea, 39.2% produced ESBLs. ESBL-producing isolates were detected in every region in Korea. A total of 44.6% of the isolates produced both TEM-and SHV-type ESBLs, and 52% of ESBL-producing isolates transferred resistance to ceftazidime by transconjugation. The ESBLs were TEM-19, TEM-20, TEM-52, SHV-2a, SHV-12, and one new variant identified for the first time in Korea, namely, TEM-116. TEM-1 and SHV-12 were by far the most common variants. TEM-1, TEM-116, and SHV-12 showed a high prevalence in K. pneumoniae. Two isolates (E. coli SH16 and K. pneumoniae SV3) produced CMY-1-like beta-lactamases, which play a decisive role in resistance to cefoxitin and cefotetan, as well as TEM-type enzymes (TEM-20 and TEM-52, respectively). Using MIC patterns and DNA sequencing analysis, we postulated a possible evolution scheme among TEM-type beta-lactamases in Korea: from TEM-1 to TEM-19, from TEM-19 to TEM-20, and from TEM-20 to TEM-52.

BackgroundThe aim of this study was to investigate the molecular epidemiological characteristics of metallo-β-lactamase (MBL)-producing Pseudomonas aeruginosa clinical isolates in Korea.Materials and MethodsThree hundred and twenty nine P. aeruginosa clinical isolates were collected from 23 general hospitals in Korea from March to June 2014. Species were identified by matrix-assited laser desorption/ionization-time of flight and 16S rRNA sequencing. Antimicrobial susceptibility was determined by disk diffusion methods. Further, minimum inhibitory concentrations of carbapenems were determined by Etest. Polymerase chain reaction and sequencing were performed to identify genes encoding MBLs. Multi-locus sequence typing and pulsed-field gel electrophoresis were performed to determine epidemiological characteristics of MBL-producing P. aeruginosa isolates.ResultsOf the 329 isolates, 229 (69.6%) were susceptible to the carbapenems tested, including imipenem and meropenem; while 100 (30.4%) were non-susceptible to more than one of the carbapenems. Genes encoding imipenemase-6 (IMP-6) and Verona imipenemase-2 (VIM-2) MBLs were identified in 21 (6.4%) isolates (n = 17 and 4, respectively). All MBL-producing isolates showed multi-drug resistant phenotype, and a majority (n = 19) of the isolates were identified as sequence type 235 (ST235). The remaining isolates (n = 2) were identified as ST309 and ST463.ConclusionP. aeruginosa ST235 might play an important role in dissemination of MBL genes in Korea.

The bla(CTX-M-14) gene was probably mobilized by IncF plasmids, which can readily spread in E. coli, causing horizontal dissemination of the resistance gene in Korea.

Although there is no consensus of the precise definition of ESBL, three kinds of ESBL definitions have been proposed. First, the classical definition includes variants derived from TEM-1, TEM-2, or SHV-1; K1 (KOXY) of Klebsiella oxytoca. Second, the broadened definition has stretched the classical definition of ESBL to include: (1) β-lactamases (CTX-M-ESBLs, GES-ESBLs, and VEB-ESBLs), with spectra similar to those of TEM and SHV variants (designated as TEM- and SHV-ESBLs, respectively) but derived from other sources; (2) TEM and SHV variants with borderline ESBL activity; e.g., TEM-12; and (3) various β-lactamases conferring wider resistance than their parent types but not meeting the definition for group 2be; e.g., OXA-types (OXA-ESBLs) and mutant AmpC-types (AmpC-ESBLs), with increased activity against oxyimino-cephalosporins and with resistance to clavulanic acid. Third, the all-inclusive definition includes: (1) ESBL(A) (named for class A ESBLs); (2) ESBL(M) (miscellaneous ESBLs), which has been subdivided into ESBL(M-C) (class C; plasmid-mediated AmpC) and ESBL(M-D) (class D); and (3) ESBL(CARBA) (ESBLs with hydrolytic activity against carbapenems), which has been subdivided into ESBL(CARBA-A) (class A carbapenemases), ESBL(CARBA-B) (class B carbapenemases), and ESBL(CARBA-D) (class D carbapenemases). The consensus view about the ESBL definition is that the classical ESBL definition must be expanded to class A non-TEM- and non-SHV-ESBLs (CTX-M-, GES-, VEB-ESBLs, etc.). However, these three definitions evoke rational debate on the question "Which would be included in the category of ESBLs among AmpC-ESBLs, OXA-ESBLs, and/or carbapenemases?" Therefore, there is a great need for consensus in the precise definition of ESBL.