Antimicrobial resistance surveillance can provide information needed for empirical therapy of antimicrobial agents and for control of resistance. To determine the trend of antimicrobial resistance in Korea, in vitro susceptibility data in 1998 were collected from 25 hospitals participating to a program of Korean Nationwide Surveillance of Antimicrobial Resistance (KONSAR). The data were analyzed based upon hospital location and bed capacity. The results showed that cefoxitin-resistant E. coli and K. pneumoniae and 3rd-generation cephalosporin-resistant K. pneumoniae were prevalent, that 3rd-generation cephalosporin-resistant E. cloacae, S. marcesens and A. baumannii had increased, and ampicillin-resistant S. enterica were not rare. Oxacillin-resistant S. aureus, penicillin-non-susceptible pneumococci and beta-lactamase-producing H. influenzae were prevalent even smaller hospitals surveyed, and an increase of imipenem-resistant P. aeruginosa and vancomycin-resistant E. faecium is a new obvious threat. In general, resistance rates to some old antimicrobial agents, i.e., E. coli to ampicillin and S. aureus to oxacillin were high and did not vary greatly between the different levels of hospitals, while the rates to some of the newer ones, i.e., P. aeruginosa to imipenem, was quite variable and depended on the hospitals, probably reflecting difference in selective pressure.
Ampicillin/pharmacology ; Anti-Infective Agents, Fluoroquinolone/pharmacology ; Bacteria/drug effects* ; Cephalosporins/pharmacology ; Drug Resistance, Microbial* ; Human ; Korea ; Time Factors

INTRODUCTIONCeftaroline is a fifth-generation cephalosporin with activity against methicillin-resistant Staphylococcus aureus (MRSA) that was recently launched in Singapore. It received approval from the United States (US) Food Drug Administration (FDA) and European Commission for the treatment of adult patients with community-acquired pneumonia (CAP) and complicated skin and soft tissue infections (cSSTI). This study aimed to review current published data and determine its clinical role, particularly in the local setting.

MATERIALS AND METHODSA literature review on published articles in English on ceftaroline, focusing in particular on clinical trials and other clinical reports. Susceptibility testing was also performed on a limited sample of local MRSA and Streptococcus pneumoniae isolates.

RESULTSCeftaroline has an extensive spectrum of activity, including coverage of MRSA and multidrug-resistant S. pneumoniae. However, it has limited activity against non-fermenting Gram-negative bacteria and is susceptible to hydrolysis by extended spectrum beta-lactamases. It is only available for intravenous delivery, with a reconstituted stability of just 6 hours, rendering it unavailable for use for outpatient antibiotic therapy. Clinical trials demonstrate non-inferiority compared to first-line comparators in the treatment of CAP and cSSTI. Published case reports/series suggest a potential greater role in the treatment of MRSA bacteremia and endocarditis. No resistance was found among local archived MRSA and S. pneumoniae isolates.

CONCLUSIONWe believe ceftaroline will occupy primarily niche roles for culture-directed treatment of various infections--in particular those caused by MRSA--until further clinical trial data become available. A variety of factors render it less useful or appealing for empirical treatment of CAP or healthcare-associated infections.

Cephalosporins ; pharmacology ; therapeutic use ; Humans ; Methicillin-Resistant Staphylococcus aureus ; drug effects ; Singapore ; Staphylococcal Infections ; drug therapy

Antimicrobial resistance is one of the critical public health issues in the world. There is an urgent need to develop effective broad-spectrum antibiotics to treat the infection of multi-drug resistant Gram-negative bacilli. Cefiderocol, developed by the Shionogi Inc. in Japan, is a new type of iron carrier cephalosporin antibiotics, which overcomes the drug resistance of Gram-negative bacilli due to the down-regulation of outer membrane pore protein and the up-regulation of efflux pump, and has good stability to serine- and metallo-carbapenemases. This drug has a broad spectrum and strong antibacterial activity against carbapenem-resistant Enterobacteriaceae (CRE), Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia. Cefiderocol can be used to treat complex urinary tract infections (including pyelonephritis), hospital-acquired pneumonia, and ventilator-associated pneumonia. By summarizing the chemical structure, antibacterial mechanism, in vitro antibacterial activity, pharmacokinetics, pharmacodynamics, and clinical treatment of cefiderocol, this review shows the application potential of cefiderocol as a new iron carrier cephalosporin in the treatment of multi-drug resistant Gram-negative bacilli infections.
Cephalosporins/therapeutic use* ; Gram-Negative Bacteria ; Microbial Sensitivity Tests ; Siderophores/pharmacology*

OBJECTIVETo study the in vitro antibacterial activity of cefdinir against clinical isolates of respiratory tract pathogens in Children.

METHODSMIC values of cefdinir against 380 strains were determined with E-test method and compared with those of cefaclor.

RESULTSAll penicillin-susceptible Streptococcus pneumoniae (PSSP) strains were also susceptible to cefdinir and cefaclor. Both cefdinir and cefaclor were not active against penicillin-resistant SP (PRSP). Against penicillin-intermediate SP (PISP) the susceptibility rates of cefdinir and cefaclor were 70.1% and 57.4%, respectively. The activity of cefdinir and cefaclor against beta-lactamases negative Hemophilus influenzae (HI) was excellent, but the susceptibility rates of cefdinir and cefaclor against beta-lactamases positive HI were 85.0% and 70.0%, respectively with MIC(90) of 1.5 mg/L vs. 256.0 mg/L. Cefdinir presented higher activities and lower MIC values than cefaclor against Moraxella catarrhalis (MC), Group A streptococcus (GAS), methicillin susceptible staphylococcus aureus (MSSA), and extended spectrum beta-lactamases (ESBLs) negative Escherichia coli (E. coli) or Klebsiella pneumoniae (K. pn). Both cefdinir and cefaclor were not susceptible to ESBLs positive E. coli and K. pn.

CONCLUSIONSCefdinir exhibits excellent activity against PSSP, PISP, HI, as well as MC, GAS, MSSA and ESBLs negative E. coli or K. pn.

Anti-Bacterial Agents ; pharmacology ; Bacteria ; drug effects ; Cephalosporins ; pharmacology ; Child ; Humans ; Microbial Sensitivity Tests ; Respiratory System ; microbiology

The 5th year KONSAR surveillance in 2001 was based on routine test data at 30 participating hospitals. It was of particular interest to find a trend in the resistances of enterococci to vancomycin, of Enterobacteriaceae to the 3rd generation cephalosporin and fluoroquinolone, and of Pseudomonas aeruginosa and acinetobacters to carbapenem. Resistance rates of Gram-positive cocci were: 70% of Staphylococcus aureus to oxacillin; 88% and 16% of Enterococcus faecium to ampicillin and vancomycin, respectively. Seventy-two percent of pneumococci were nonsusceptible to penicillin. The resistance rates of Enterobacteriaceae were: Escherichia coli, 28% to fluoroquinolone; Klebsiella pneumoniae, 27% to ceftazidime, and 20% to cefoxitin; and Enterobacter cloacae, > or =40% to cefotaxime and ceftazidime. The resistance rates of P. aeruginosa were 21% to ceftazidime, 17% to imipenem, and those of the acinetobacters were > or =61% to ceftazidime, aminoglycosides, fluoroquinolone and cotrimoxazole. Thirty-five percent of non-typhoidal salmonellae were ampicillin resistant, and 66% of Haemophilus influenzae were -lactamase producers. Notable changes over the 1997-2001 period were: increases in vancomycin-resistant E. faecium, and amikacin- and fluoroquinolone-resistant acinetobacters. With the increasing prevalence of resistant bacteria, nationwide surveillance has become more important for optimal patient management, for the control of nosocomial infection, and for the conservation of the newer antimicrobial agents.
Anti-Bacterial Agents/*pharmacology ; Cephalosporins/pharmacology ; *Drug Resistance, Microbial ; Enterococcus faecium/metabolism ; Human ; Imipenem/pharmacology ; Klebsiella pneumoniae/metabolism ; Korea ; Pseudomonas aeruginosa/metabolism ; Time Factors ; Vancomycin/*pharmacology

Antimicrobial resistance surveillance is necessary to determine the size of the problem and to guide empirical selection of antimicrobial agents for treating infected patients. The aim of this study was to analyze the results of susceptibility tests performed by hospitals participating in the Korean Nationwide Surveillance of Antimicrobial Resistance (KONSAR) program. The rates of oxacillin-resistant staphylococci, penicillin-nonsusceptible pneumococci, and ampicillin-resistant E. faecium were over 70%. Ampicillin-resistant H. influenzae increased to 68%. Expanded-spectrum cephalosporin-resistant K. pneumoniae, fluoroquinolone-resistant E. coli, and imipenem-resistant P. aeruginosa remained at 16% through 27%, depending on the species. The proportions of vancomycin-resistant E. faecium and imipenem-resistant P. aeruginosa were 18 - 24% and 19-21%, respectively, indicating the seriousness of antimicrobial resistance. In conclusion, the increasing prevalence of resistant bacteria indicates that more concerted effort is required to conserve the usefulness of precious new antimicrobial agents.
Anti-Bacterial Agents/*pharmacology ; Cephalosporins/*pharmacology ; *Drug Resistance, Microbial ; Enterococcus/*drug effects ; Gram-Negative Bacteria/*drug effects ; Human ; Imipenem/*pharmacology ; Korea ; *Vancomycin Resistance

OBJECTIVETo analyze the distribution of Enterobacteriaceae isolated from West China Hospital, investigate the antibiotic resistance profile of Enterobacteriaceae with decreased susceptibility to carbapenems and explore the molecular mechanism.

METHODSForty-five Enterobacteriaceae strains resistant or with reduced susceptibility to carbapenems were isolated from patients in West China Hospital. The antimicrobial susceptibility and carbapenemase-producing phenotypes of the bacteria were examined and specific PCR were performed to determine the molecular mechanism.

RESULTSOf the 45 isolates, 17, 21 and 36 were resistant or intermediate strains to imipenem, meropenem and ertapenem, respectively. The majority of these isolates showed resistance to cephalosporins. The modified Hodge test resulted in the highest positivity rate (77.8%), followed by EDTA disc test (57.8%) and PBA disc test (22.2%). BlaTEM, blaSHV and blaCTX-M were detected in 60.0%, 53.3% and 15.6% of these strains with reduced susceptibility. The rate of strains carrying 2 or more genes was 44.4%, and the detection rate of blaIMP was 48.9%. BlaKPC was identified in 4 (8.9%) high-level resistant strains and confirmed to locate on the plasmid.

CONCLUSIONProduction of carbapenemase contributes to reduced susceptibility of carbapenems in Enterobacteriaceae. The presence of blaKPC, MBL and ESBL, and their possible combinations can be the main factor contributing to carbapenem resistance or reduced susceptibility in Enterobacteriaceae. The KPC-2 carbapenemase gene located on the plasmids we found in this study can cause potential horizontal transmission across strains.

Anti-Bacterial Agents ; pharmacology ; Bacterial Proteins ; genetics ; metabolism ; Carbapenems ; pharmacology ; Cephalosporins ; pharmacology ; Enterobacteriaceae ; drug effects ; enzymology ; genetics ; Gene Amplification ; Imipenem ; pharmacology ; Microbial Sensitivity Tests ; Polymerase Chain Reaction ; Thienamycins ; pharmacology ; beta-Lactam Resistance ; beta-Lactamases ; genetics ; metabolism ; beta-Lactams ; pharmacology

The in vitro antibacterial activities of oral cephem antibiotics and ketolide telithromycin against major respiratory pathogens possessing beta-lactam-resistant mutations (within the pbp gene) and/or macrolide-resistant genes (erm and mef) were examined in clinical isolates collected at 66 institutes in all over the Japan between 2002 and 2003. Telithromycin showed the strongest antibacterial activity against methicillinsusceptible Staphylococcus aureus strains with and without macrolide-resistant genes, such as ermA or ermC gene. All the cephem antibiotics showed potent antibacterial activity against Streptococcus pyogenes, with minimum inhibitory concentrations (MICs) of 0.015 mg/L or lower. Cefdinir had a much higher MIC90 against genotypic penicillin-resistant Streptococcus pneumoniae (gPRSP) than cefditoren and cefcapene (8 mg/L cefdinir vs. 1 mg/L cefditoren and cefcapene). The majority of gPRSP harbored either ermB or mefA, and the antibacterial activity of telithromycin against these strains was decreased however some susceptibility was still sustained. Cefditoren exerted the strongest antibacterial activity against beta-lactamase-negative ampicillin-resistant Haemophilus influenzae, with an MIC90 of 0.5 mg/L. These results underline the importance of checking the susceptibility and selecting an appropriate antibiotic against target pathogens.
Streptococcus pyogenes/*drug effects ; Streptococcus pneumoniae/*drug effects ; Staphylococcus aureus/*drug effects ; Microbial Sensitivity Tests ; Methicillin Resistance ; Ketolides/*pharmacology ; Humans ; Haemophilus influenzae/*drug effects ; Cephalosporins/*pharmacology ; Administration, Oral

AIMNineteen compounds related to salicylic acid were evaluated for their in vitro activity of inhibiting beta-lactamase isolated from a resistant strain of Pseudomonas aeruginosa, and their structure-activity relationships were examined.

METHODSNitrocefin method was used.

RESULTSThe 50% inhibitory concentration (IC50) of salicylic acid inhibiting beta-lactamase was 22 mmol x L(-1); four analogs had IC50 lower than that of salicylic acid; fifteen analogs had IC50 higher than that of salicylic acid.

CONCLUSIONExamination of the structure-activity relationships of the compounds revealed that carboxyl group and adjoining hydroxyl group were active group, and replacement of adjoining hydroxyl by carboxyl increased activity nearly 4-fold. Moreover, addition of a sulfonic group at C-5 and nitro group at C-3, 5 of benzenoic ring of salicylic acid resulted in a 2-fold to 3-fold increase in activity, addition of a amino group at C-5 of benzenoic ring of salicylic acid decreased activity, add addition of -Cl or -F at C-2,4 position of benzenoic ring of benzoic acid did not show activity.

Anti-Bacterial Agents ; chemical synthesis ; chemistry ; pharmacology ; Cephalosporins ; metabolism ; Inhibitory Concentration 50 ; Pseudomonas aeruginosa ; enzymology ; Salicylates ; chemical synthesis ; chemistry ; pharmacology ; Structure-Activity Relationship ; beta-Lactamases ; isolation & purification ; metabolism

OBJECTIVETo investigate the change in the antibiotic resistant spectrum of Pseudomonas aeruginosa (PA) isolated from burn wounds and the production of inducible beta-lactamase.

METHODSVITEK-AMS system (total automatic bacterial identification and drug sensitivity system) and E-test concentration gradient were employed to perform bacterial identification and antibiotic sensitivity tests. K-B method was applied to detect inducible enzyme.

RESULTSThe resistance of PA to Cephalosporin and Imipenem was increased in the past 4 years from June of 1996 to June of 2000. Whereas the resistance to Cefoperazone/Sulbactam was least. There was an obvious difference of the resistance of PA to antibiotics during the 4 years (P < 0.05). The resistant rate to Imipenem ranged from 20% to 40%. PA was able to produce inducible enzymes among 120 strains of wild type of PA occupying 72.5% with Imipenam as the inducing agent.

CONCLUSIONThe analysis of the antibiotic resistance of PA and the detection of inducible enzymes could be monitored from time to time and helpful in the correction of the use of antibiotics. Constant monitoring of antibiotic resistance might be beneficial to the prevention of outbreak of epidemics of PA infection in a burn unit.

Burns ; microbiology ; Cephalosporins ; pharmacology ; Drug Resistance, Bacterial ; Enzyme Induction ; Humans ; Imipenem ; pharmacology ; Microbial Sensitivity Tests ; Pseudomonas aeruginosa ; drug effects ; isolation & purification