The emergence of carbapenem-resistant Gram-negative pathogens poses a serious threat to public health worldwide. In particular, the increasing prevalence of carbapenem-resistant Klebsiella pneumoniae is a major source of concern. K. pneumoniae carbapenemases (KPCs) and carbapenemases of the oxacillinase-48 (OXA-48) type have been reported worldwide. New Delhi metallo-β-lactamase (NDM) carbapenemases were originally identified in Sweden in 2008 and have spread worldwide rapidly. In this review, we summarize the epidemiology of K. pneumoniae producing three carbapenemases (KPCs, NDMs, and OXA-48-like). Although the prevalence of each resistant strain varies geographically, K. pneumoniae producing KPCs, NDMs, and OXA-48-like carbapenemases have become rapidly disseminated. In addition, we used recently published molecular and genetic studies to analyze the mechanisms by which these three carbapenemases, and major K. pneumoniae clones, such as ST258 and ST11, have become globally prevalent. Because carbapenemase-producing K. pneumoniae are often resistant to most β-lactam antibiotics and many other non-β-lactam molecules, the therapeutic options available to treat infection with these strains are limited to colistin, polymyxin B, fosfomycin, tigecycline, and selected aminoglycosides. Although, combination therapy has been recommended for the treatment of severe carbapenemase-producing K. pneumoniae infections, the clinical evidence for this strategy is currently limited, and more accurate randomized controlled trials will be required to establish the most effective treatment regimen. Moreover, because rapid and accurate identification of the carbapenemase type found in K. pneumoniae may be difficult to achieve through phenotypic antibiotic susceptibility tests, novel molecular detection techniques are currently being developed.

BackgroundAppendicitis is one of the most frequent acute surgical conditions of the abdomen, and appendectomy is one of the most commonly performed operations in the world. However, epidemiological data on appendicitis have not been reported for South Korean or East Asian populations.MethodsWe analyzed the epidemiological features and lifetime risk of appendicitis and appendectomy in South Korea using data collected for the national health insurance database from 2005 through 2007.ResultsAppendectomy was performed in 59.70% of inpatients diagnosed with appendicitis. The overall incidences of appendicitis, total appendectomy, and perforated appendectomy were 22.71, 13.56, and 2.91 per 10 000 population per year, respectively. The incidence of appendicitis and appendectomy showed clear seasonality, with a peak in summer. The standardized lifetime risks of appendicitis and appendectomy were constant from 2005 through 2007. A life table model suggests that the lifetime risk of appendicitis is 16.33% for males and 16.34% for females, and that the lifetime risk of appendectomy is 9.89% for males and 9.61% for females.ConclusionsAs compared to results obtained in research on Western populations, appendicitis and appendectomy had a similar perforation rate and seasonality, but a higher overall incidence, in South Koreans. Between 2005 and 2007, the incidence of appendicitis and appendectomy was constant. Overall, an estimated 15 incidental appendectomies are performed to prevent 1 inpatient with suspected appendicitis, and 26 incidental appendectomies are performed to prevent 1 appendectomy. Incidental appendectomy may have greater preventive value in Koreans.

Carbapenems (imipenem, meropenem, biapenem, ertapenem, and doripenem) are β-lactam antimicrobial agents. Because carbapenems have the broadest spectra among all β-lactams and are primarily used to treat infections by multi-resistant Gram-negative bacteria, the emergence and spread of carbapenemases became a major public health concern. Carbapenemases are the most versatile family of β-lactamases that are able to hydrolyze carbapenems and many other β-lactams. According to the dependency of divalent cations for enzyme activation, carbapenemases can be divided into metallo-carbapenemases (zinc-dependent class B) and non-metallo-carbapenemases (zinc-independent classes A, C, and D). Many studies have provided various carbapenemase structures. Here we present a comprehensive and systematic review of three-dimensional structures of carbapenemase-carbapenem complexes as well as those of carbapenemases. We update recent studies in understanding the enzymatic mechanism of each class of carbapenemase, and summarize structural insights about regions and residues that are important in acquiring the carbapenemase activity.

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...