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PubMed1997

Vancomycin-resistant Enterococcus raffinosus: molecular epidemiology, species identification error, and frequency of occurrence in a national resistance surveillance program.

Enterococcal blood stream infections are the third most common among all nosocomial blood stream infections in the United States and the occurrence of glycopeptide (vancomycin, teicoplanin) resistance in these isolates has markedly increased. Control of hospital-acquired infections with vancomycin-resistant enterococci requires high quality antimicrobial susceptibility test methods and species identification procedures as a supplement to epidemiologic investigation and appropriate infection control procedures. In this report, bacteremias caused by Enterococcus avium (BioMerieux Vitek, Hazelwood, MO, USA) were observed to be Enterococcus raffinosus infections (six of eight cases; 1.1% of all cases) when reference biochemical identification methods were applied. The vancomycin-susceptible E. raffinosis (two strains) and E. avium (two strains) had unique phenotypic and genotypic molecular profiles. In contrast, four vancomycin-resistant E. raffinosus strains (van A by polymerase chain reaction) from a single institution had the same phenotypic and molecular (PCR, PFGE, ribotyping) pattern, indicating clonal dissemination among four patients over a 66-day period. Clinical laboratories should be aware of the high probability that van A genes may be transferred from Enterococcus faecium or Enterococcus faecalis to other more rarely encountered Enterococcus species. Also contemporary, widely used commercial identification systems may fail to accurately identify those rare species. Errors appear to be most prevalent for E. avium, Enterococcus durans, and E. raffinosus based on the experience of the SCOPE Program.

Anti-Bacterial Agents↗

PubMed1996

Comparative in-vitro activity of the new fluoroquinolone trovafloxacin (CP-99,219) against gram-positive cocci.

The in-vitro activities of the new fluoroquinolone trovafloxacin (CP-99,219) and ciprofloxacin were determined against 225 Gram-positive cocci. Trovafloxacin was 4-32 fold more active than ciprofloxacin against staphylococci and streptococci and also showed greater activity against enterococci including vancomycin resistant Enterococcus faecium and Enterococcus faecalis that were highly resistant to aminoglycosides and/or produced beta-lactamase. Trovafloxacin was also bactericidal at 3 mg/L against enterococci except for isolates for which the MICs were > or = 2 mg/L.

Anti-Infective Agents↗

PubMed2000

Enterococcal glycopeptide resistance at an Italian teaching hospital.

Two thousand one hundred and thirteen strains of enterococci isolated at Pisa General Hospital in 1998 were analysed retrospectively to determine their glycopeptide resistance. Of all the microorganisms isolated in this period, 14.7% were enterococci (1405 Enterococcus faecalis, 19 Enterococcus faecium, six Enterococcus avium and 683 Enterococcus spp.). Two hundred and thirty (10.8%) of these enterococci were resistant or demonstrated reduced susceptibility to vancomycin and/or teicoplanin. The highest rate of resistance was found in outpatient enterococcal strains isolated from the urogenital tract. The frequency of enterococcal glycopeptide resistance at Pisa Hospital is higher than that reported from other areas of Italy.

Anti-Bacterial Agents↗

PubMed2000

Enterococci with reduced susceptibility to vancomycin in New Zealand.

This study was conducted to determine the prevalence of vancomycin-resistant enterococci (VRE) in the stools of hospitalized patients with possible antibiotic-associated diarrhoea. From 176 faecal samples collected during 1997 and 1998, 66 strains of enterococci were recovered using vancomycin enrichment techniques. Only six of these displayed reduced susceptibility to vancomycin (MIC 8-12 mg/L). All VRE were positive for the presence of the vanC gene. Based on motility, pigment production and automated Gram-positive identification (GPI Vitek card), four of these six VRE isolates were identified as Enterococcus gallinarum. The remaining two isolates were non-motile and therefore were considered to be Enterococcus faecium. However, 16S rDNA sequence analysis and positive methyl-alpha-D-glucopyranoside tests indicated that they were non-motile species of E. gallinarum. This is consistent with the intrinsic, low-level vanC-1-mediated resistance associated with this species. Pulsed-field gel electrophoresis analysis comparisons between the VRE indicated genetic relatedness between some strains. This work confirms that vancomycin-resistant E. faecium and Enterococcus faecalis are rare in New Zealand.

Anti-Bacterial Agents↗

PubMed2003

Ramoplanin: a novel antimicrobial agent with the potential to prevent vancomycin-resistant enterococcal infection in high-risk patients.

The prevention of vancomycin-resistant Enterococcus (VRE) colonization and infection continues to be a high priority for clinicians. An oral antimicrobial agent that reduces or eliminates VRE gastrointestinal colonization could be useful for preventing VRE infection in selected patients. Ramoplanin, a glycolipodepsipeptide, is the first in a new class of antimicrobials. It has excellent in vitro activity against vancomycin-resistant Enterococcus faecium and Enterococcus faecalis. It is orally administered, and not absorbed systemically. In clinical trials, VRE gastrointestinal colonization was reduced to undetectable levels in 80-90% of patients during receipt of ramoplanin. A randomized, double-blinded, placebo-controlled multicentre study is currently being conducted to determine whether ramoplanin will prevent VRE bloodstream infection in oncology patients who are neutropenic due to treatment for a haematological malignancy or a bone marrow/stem cell transplant.

Anti-Bacterial Agents↗

PubMed1998

Enterococcal bacteremia in children: a review of seventy-five episodes in a pediatric hospital.

BACKGROUND: Enterococcal bacteremia is being increasingly reported. Although there have been a number of recent studies of enterococcal bacteremia in adults, there are few studies involving children. We carried out a prospective study to determine the epidemiologic, clinical and laboratory characteristics of such bacteremia in children. METHODS: Clinical and microbiologic data were recorded prospectively for all episodes of enterococcal bacteremia occurring during a 3-year period between January 1, 1995, and December 31, 1997. RESULTS: Seventy-five episodes of enterococcal bacteremia occurring in children at our institution during a 3-year period were prospectively analyzed. Serious underlying disease was present in 67 (89.3%) episodes, and in 48 (64.%) episodes patients had received antibiotics during the 2 weeks preceding enterococcal bacteremia. Forty-seven (62.7%) episodes were nosocomial in origin and 26 (34.7%) were polymicrobial. Fifty (66.7%) episodes occurred in children 1 year old or less. A source of bacteremia was identified in 33 (44%) episodes, intravascular device being the most common identifiable source. Of the 73 isolates identified to species level, there were 36 Enterococcus faecium, 36 Enterococcus faecalis and one Enterococcus avium. In 60 (80%) episodes appropriate anti-enterococcal therapy was given. The overall mortality rate was 7.5%. Four clinical patterns of infection were identified: self-limited bacteremia, 16.0%; low grade sepsis with a favorable outcome after specific therapy, 65.3%; severe and prolonged infection associated with a high mortality rate, 14.7%; and fulminant neonatal sepsis in previously healthy babies, 4.0%. CONCLUSION: Enterococcal bacteremia in children comprises a heterogeneous group. Bacteremias that are mild and self-limited and respond promptly to antibiotic therapy appear to be more common in children.

Adolescent↗

PubMed1997

Evaluation of arbitrarily primed PCR analysis and pulsed-field gel electrophoresis of large genomic DNA fragments for identification of enterococci important in human medicine.

The increasing problems encountered with enterococcal nosocomial infections and the intrinsic and acquired resistance of the enterococci to different antimicrobial compounds highlight the need for a rapid identification technique. Enterococcus faecalis is readily identified by biochemical tests, but species differentiation within the Enterococcus faecium and Enterococcus gallinarum species groups is less well established. In the present study, 66 strains representing the most prevalent human enterococci were used to develop a PCR-based species-specific identification protocol. Whole-cell protein analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used as a reference method for species identification. In addition, the genomic SmaI macro-restriction fragment distribution of all of the strains was examined by pulsed-field gel electrophoresis (PFGE). Oligonucleotide D11344-primed PCR was as discriminative as whole-cell protein analysis and resulted in more easily interpreted band patterns. This PCR-based technique allowed identification of clinical isolates by visual examination of the DNA profiles obtained. The inability of both methods to discriminate between Enterococcus casseliflavus and Enterococcus flavescens brought into question the species status of E. flavescens. PFGE did not result in species-discriminative DNA bands or band patterns, but proved to be superior for interpretation of interstrain relationships.

Bacterial Typing Techniques↗

PubMed1998

Enterococcus asini sp. nov. isolated from the caecum of donkeys (Equus asinus).

Several Gram-positive, non-spore-forming and non-motile bacteria consisting of pairs or chains of cocci were isolated during an investigation of the bacterial flora of the caecum of donkeys. Physiological and metabolic data indicated that the strains belong to the genus Enterococcus; phenotypic traits of these organisms were not consistent with any of the currently known Enterococcus species. 16S rRNA gene sequence analysis placed these strains in the genus Enterococcus. Their closest relatives are Enterococcus avium, Enterococcus faecium and Enterococcus pseudoavium with a sequence similarity of 97.4%. This group of strains can be differentiated from the other Enterococcus spp. by their phenotypic characteristics: strains do not grow in 6.5% NaCl; they do not produce acid from mannitol, sorbitol, sorbose, sucrose, raffinose, ribose and tagatose; they produce acid from D-xylose; they are able to utilize pyruvate; and they present a negative reaction on arginine. The name Enterococcus asini sp. nov. is proposed for these strains; the type strain is AS2T (= DSM 11492T).

Animals↗

PubMed2004

Antimicrobial susceptibility testing of vancomycin-resistant Enterococcus by the VITEK 2 system, and comparison with two NCCLS reference methods.

We evaluated the automated VITEK 2 system (bioMerieux) for antimicrobial susceptibility testing of vancomycin-resistant Enterococcus (VRE). The results obtained with the VITEK 2 system were compared to those obtained using two NCCLS reference methods. The VITEK 2 system produced MICs for penicillin G, erythromycin and vancomycin that were very similar to those of the reference agar-dilution test with all results being within a twofold dilution. When MICs of teicoplanin for these isolates were measured by the agar-dilution method and VITEK 2 system, there was one 'very major' error and seven 'minor' errors. There were no 'major' errors for any of the antibiotics tested. When the results obtained by the micro broth-dilution method were compared with those obtained by the VITEK 2 system, there was one 'very major' error for teicoplanin by the VITEK 2 system, as was the case with the agar-dilution method. There were two 'minor' errors for erythromycin and seven 'minor' errors for teicoplanin. There were no 'major' errors for any of the antibiotics tested. The 35 VRE strains identified phenotypically by the VITEK 2 Advanced Expert System included nine of Enterococcus faecalis and 23 of Enterococcus faecium. Neither Enterococcus avium nor Enterococcus hirae were identified. A total of 32 phenotypes were classified into 22 VanA and 10 VanB strains. PCR genotyping demonstrated 23 vanA+ and nine vanB+ strains. There were differences between the VITEK 2 system results and those of PCR. Overall, 54.3 % of the test results were obtained within 7 h. All MIC values for the 35 VRE isolates were determined within 13 h of completing incubation. The VITEK 2 system is a simple method for accurately detecting vancomycin-resistant strains of Enterococcus and can be used to rapidly determine MICs.

Anti-Bacterial Agents↗

PubMed1991

[Clinical features of enterococcal septicemia and antimicrobial susceptibilities for clinical isolates of enterococci in Nagoya University Hospital].

Enterococci are important causative organisms of nosocomial infections as well as methicillin resistant Staphylococcus aureus and Pseudomonas aeruginosa. Enterococcal bacteremia has been increased in Nagoya University Hospital from April 1983 to March 1990. We analyzed the clinical backgrounds, portal of entry and mortality for the patients with Enterococcal septicemia. Thirty-four cases with enterococcal septicemia (24 Enterococcus faecalis, 10 Enterococcus faecium) were subjected in this study. Twenty-seven cases were monomicrobial septicemia and 7 cases were polymicrobial septicemia. As to the portal of entry, intra-abdominal infections in 21 cases, urinary tract infections in 4 cases, respiratory tract infections or chest tubes in 2 cases, decbitus infection in 1 case, intravascular catheter in 1 case, and unknown sources in 5 cases. Total mortality of the septicemia was 44.1%. E. faecium and Enterococcus avium were much more resistant to antimicrobial agents than E. faecalis. Enterococci with high-level resistance to gentamicin (minimal inhibitory concentration, greater than 2000 micrograms/ml) accounted for 35% of the 26 clinical isolates of enterococci.

Adolescent↗

PubMed1995

[Drug sensitivity and expression of beta-lactamase in enterococci isolated at Okayama University Hospital].

The following results were obtained from a study of Enterococci isolated at the Okayama University Hospital from 1990 to 1994. 1) The isolation frequency of Enterococci was about 6% for each year. 2) The percentage of Enterococcus faecalis (E. faecalis) among Enterococci decreased each year, but the percentage of Enterococcus faecium (E. faecium), and Enterococcus avium (E. avium) increased each year. 3) Results of drug sensitivity tests revealed that the incidence of ofloxacin (OFLX) resistant E. faecalis and E. avium increased each year. Also, the resistance of E. faecalis to ampicillin (ABPC), the primary medication choice for treating E. faecalis, increased each year. 4) A few vancomycin (VCM) non-sensitive Enterococci were isolated. These bacteria showed low-sensitivity toward ABPC, imipenem (IPM), gentamicin (GM), and OFLX, and the extent of multiple drug resistance increased each year. 5) One hundred strains of Enterococci were selected to examine the expression of beta-lactamase using the broth method and the iodine-starch method. However, beta-lactamase producing strains were not detected.

Anti-Bacterial Agents↗

PubMed1997

Semiquantitation of cooperativity in binding of vancomycin-group antibiotics to vancomycin-susceptible and -resistant organisms.

The association of vancomycin group antibiotics with the growing bacterial cell wall was investigated by using the cell wall precursor analog di-N-acetyl-Lys-D-Ala-D-Ala in competition binding experiments. The affinities of the antibiotics for the -D-Ala-D-Ala-containing cell wall precursors of Bacillus subtilis ATCC 6633 (a model for vancomycin-susceptible gram-positive bacteria) and for the -D-Ala-D-Lac-containing cell wall precursors of Leuconostoc mesenteroides (a model for vancomycin-resistant strains of Enterococcus faecium and Enterococcus faecalis) were determined by a whole-cell assay. The binding of strongly dimerizing antibiotics such as eremomycin to the bacterial surface was thus shown to be enhanced by up to 2 orders of magnitude (relative to the binding in free solution) by the chelate effect, whereas weakly dimerizing antibiotics like vancomycin and antibiotics carrying lipid tails (teicoplanin) benefited less (ca. 1 order of magnitude). The affinity measured in this way correlates well with the MIC of the antibiotic, and a consequence of this is that future design of semisynthetic vancomycin-group antibiotics should attempt to incorporate chelate effect-enhancing structural features.

Anti-Bacterial Agents↗

PubMed2003

MC21-A, a bactericidal antibiotic produced by a new marine bacterium, Pseudoalteromonas phenolica sp. nov. O-BC30(T), against methicillin-resistant Staphylococcus aureus.

We previously reported a new marine bacterium, Pseudoalteromonas phenolica sp. nov. O-BC30(T), which produced a bactericidal antibiotic against methicillin-resistant Staphylococcus aureus (MRSA). In the present study, we purified an anti-MRSA substance (MC21-A) from the methanol extract of the cells of P. phenolica O-BC30(T) and analyzed its chemical structure. MC21-A was determined to be 3,3',5,5'-tetrabromo-2,2'-biphenyldiol by spectrometric analyses. Its anti-MRSA activity against 10 clinical isolates of MRSA was comparable to that of vancomycin (MC21-A MICs, 1 to 2 micro g/ml; vancomycin MICs, <0.25 to 2 micro g/ml). This substance was also high active against Enterococcus serolicida, Enterococcus faecium, and Enterococcus faecalis but was less active against Streptococcus spp. A time-kill study also demonstrated that MC21-A was bactericidal and that its killing rate was much higher than that of vancomycin. The postantibiotic effect (PAE) of MC21-A against a clinical MRSA isolate, strain E 31243, was also comparable to that of vancomycin (MC21-A PAEs, 1.46 to 1.65 h; vancomycin PAEs, 0.84 to 1.43 h). However, a lysis experiment demonstrated that this substance failed to lyse MRSA cells. This substance also did not lyse human erythrocytes. A SYTOX Green staining experiment implied that this substance permeabilized the cell membrane of MRSA as its mode of action. When its activities against a hypersensitive Escherichia coli mutant (KO 1489) and wild-type strains were tested, MC21-A exhibited higher levels of activity against the former. Furthermore, MC21-A was not cytotoxic to human normal fibroblast, rat pheochromocytoma, and Vero cells at concentrations up to 50 micro g/ml. These results suggest that MC21-A might be useful as a lead compound in the development of new types of anti-MRSA substances with modes of action different from those of vancomycin and teicoplanin.

Anti-Bacterial Agents↗

PubMed1997

Cloning of the Staphylococcus aureus ddh gene encoding NAD+-dependent D-lactate dehydrogenase and insertional inactivation in a glycopeptide-resistant isolate.

The mechanism of low-level glycopeptide resistance among staphylococci is not known. A cytoplasmic protein, provisionally called Ddh (W. M. Milewski, S. Boyle-Vavra, B. Moreira, C. C. Ebert, and R. S. Daum, Antimicrob. Agents Chemother. 40:166-172, 1996), and the RNA transcript that contains the ddh gene, which encodes Ddh, are present in increased amounts in a vancomycin-resistant isolate, 523k, compared with the susceptible parent isolate, 523. Sequence analysis had previously revealed that Ddh is related to NAD+-dependent D-lactate dehydrogenase (D-nLDH) and VanH. This latter protein is essential for high-level glycopeptide resistance in Enterococcus faecium and Enterococcus faecalis by synthesizing the D-lactate needed for biosynthesis of D-lactate-terminating peptidoglycan precursors with low affinity for vancomycin. We now provide the direct evidence that the ddh gene product is Staphylococcus aureus D-nLDH and hereafter refer to the protein as D-nLDH. However, overproduction of this protein in isolate 523k did not result in production of D-lactate-containing peptidoglycan precursors, and susceptibility testing of ddh mutants of 523k demonstrated that S. aureus D-nLDH is not necessary for glycopeptide resistance in this isolate. We conclude that the mechanism of glycopeptide resistance in this isolate is distinct from that in enterococci.

Alcohol Oxidoreductases↗

PubMed2002

Enterococcus faecalis acetoacetyl-coenzyme A thiolase/3-hydroxy-3-methylglutaryl-coenzyme A reductase, a dual-function protein of isopentenyl diphosphate biosynthesis.

Many bacteria employ the nonmevalonate pathway for synthesis of isopentenyl diphosphate, the monomer unit for isoprenoid biosynthesis. However, gram-positive cocci exclusively use the mevalonate pathway, which is essential for their growth (E. I. Wilding et al., J. Bacteriol. 182:4319-4327, 2000). Enzymes of the mevalonate pathway are thus potential targets for drug intervention. Uniquely, the enterococci possess a single open reading frame, mvaE, that appears to encode two enzymes of the mevalonate pathway, acetoacetyl-coenzyme A thiolase and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. Western blotting revealed that the mvaE gene product is a single polypeptide in Enterococcus faecalis, Enterococcus faecium, and Enterococcus hirae. The mvaE gene was cloned from E. faecalis and was expressed with an N-terminal His tag in Escherichia coli. The gene product was then purified by nickel affinity chromatography. As predicted, the 86.5-kDa mvaE gene product catalyzed both the acetoacetyl-CoA thiolase and HMG-CoA reductase reactions. Temperature optima, DeltaH(a) and K(m) values, and pH optima were determined for both activities. Kinetic studies of acetoacetyl-CoA thiolase implicated a ping-pong mechanism. CoA acted as an inhibitor competitive with acetyl-CoA. A millimolar K(i) for a statin drug confirmed that E. faecalis HMG-CoA reductase is a class II enzyme. The oxidoreductant was NADP(H). A role for an active-site histidine during the first redox step of the HMG-CoA, reductase reaction was suggested by the ability of diethylpyrocarbonate to block formation of mevalonate from HMG-CoA, but not from mevaldehyde. Sequence comparisons with other HMG-CoA reductases suggest that the essential active-site histidine is His756. The mvaE gene product represents the first example of an HMG-CoA reductase fused to another enzyme.

Acyl Coenzyme A↗

PubMed1990

Species identities of enterococci isolated from clinical specimens.

Conventional tests and commercially available systems were used to determine the species identities of clinical isolates of enterococci. Strict adherence to the conventional test scheme of Facklam and Collins (R. R. Facklam and M. D. Collins, J. Clin. Microbiol. 27:731-734, 1989) resulted in the misidentification of lactose-negative Enterococcus faecalis isolates as Enterococcus solitarius, but this problem was overcome by the application of additional tests. The commercially available systems tested were unable to recognize some of the more recently described enterococcal species. E. faecalis accounted for 87.1% of 302 consecutive isolates. Enterococcus faecium (8.6%), Enterococcus avium (0.7%), Enterococcus durans (0.3%), Enterococcus gallinarum (1.0%), Enterococcus casseliflavus (1.0%), Enterococcus hirae (0.3%), and Enterococcus raffinosus (0.3%) isolates were also identified. None of the isolates produced beta-lactamase, but 15.4% of 235 isolates tested, including 1 strain of E. gallinarum, displayed high-level resistance to gentamicin.

Culture Media↗

PubMed2004

Prevalence and characterization of integrons in blood culture Enterobacteriaceae and gastrointestinal Escherichia coli in Norway and reporting of a novel class 1 integron-located lincosamide resistance gene.

BACKGROUND: Class 1 integrons contain genetic elements for site-specific recombination, capture and mobilization of resistance genes. Studies investigating the prevalence, distribution and types of integron located resistance genes are important for surveillance of antimicrobial resistance and to understand resistance development at the molecular level. METHODS: We determined the prevalence and genetic content of class 1 integrons in Enterobacteriaceae (strain collection 1, n = 192) and E. coli (strain collection 2, n = 53) from bloodstream infections in patients from six Norwegian hospitals by molecular techniques. Class 1 integrons were also characterized in 54 randomly selected multiresistant E. coli isolates from gastrointestinal human infections (strain collection 3). RESULTS: Class 1 integrons were present in 10.9% of the Enterobacteriaceae blood culture isolates of collection 1, all but one (S. Typhi) being E. coli. Data indicated variations in class 1 integron prevalence between hospitals. Class 1 integrons were present in 37% and 34% of the resistant blood culture isolates (collection 1 and 2, respectively) and in 42% of the resistant gastrointestinal E. coli. We detected a total of 10 distinct integron cassette PCR amplicons that varied in size between 0.15 kb and 2.2 kb and contained between zero and three resistance genes. Cassettes encoding resistance to trimethoprim and aminoglycosides were most common. We identified and characterized a novel plasmid-located integron with a cassette-bound novel gene (linF) located downstream of an aadA2 gene cassette. The linF gene encoded a putative 273 aa lincosamide nucleotidyltransferase resistance protein and conferred resistance to lincomycin and clindamycin. The deduced LinF amino acid sequence displayed approximately 35% identity to the Enterococcus faecium and Enterococcus faecalis nucleotidyl transferases encoded by linB and linB' CONCLUSIONS: The present study demonstrated an overall low and stable prevalence of class 1 integron gene cassettes in clinical Enterobacteriaceae and E. coli isolates in Norway. Characterization of the novel lincosamide resistance gene extends the growing list of class 1 integron gene cassettes that confer resistance to an increasing number of antibiotics.

Journal Article↗

PubMed2003

[Nationwide sensitivity surveillance of ciprofloxacin and various parenteral antibiotics against bacteria isolated from patients with severe infections--the first Ciproxan IV special investigation in 2001].

The parenteral injection of ciprofloxacin (CPFX), a fluoroquinolone antimicrobial drug, was approved in September 2000 and a re-examination period of 6 years was set at that time. As a special investigation to apply for re-examination of this drug, it has been planned to conduct 3 nationwide surveillances during the re-examination period by collecting clinically isolated bacteria from patients with severe infections, to whom the drug was mainly indicated, and examining drug susceptibilities of the bacteria to various parenteral antimicrobial drugs including CPFX. This time, we determined the minimum inhibitory concentrations (MICs) of various parenteral antimicrobial drugs including CPFX against 1,220 strains isolated from patients with severe infections by the micro-liquid dilution method and compared susceptibilities of various clinically isolated bacteria to CPFX with those to other antimicrobial drugs. Gram-positive bacteria were less susceptible to CPFX than to carbapenems except 2 bacterial species, Enterococcus faecium and Enterococcus avium but susceptibilities of methicillin-susceptible Staphylococcus aureus (MSSA), Staphylococcus epidermidis and Enterococcus faecalis to CPFX were comparable to those to cefozopran. Susceptibility of Streptococcus pneumoniae to CPFX did not differ among ampicillin (ABPC)-susceptible Streptococcus pneumoniae (MIC of ABPC: < 0.25 microgram/ml), ABPC-intermediate S. pneumoniae (MIC of ABPC: 0.25-2 micrograms/ml) and ABPC-resistant S. pneumoniae (MIC of ABPC: > or = 4 micrograms/ml) MIC90 of CPFX: 1 microgram/ml) and a decrease in the antimicrobial activity seen among cephem and carbapenem antimicrobial drugs against penicillin-intermediate strains was not noted with CPFX. Gram-negative bacteria were susceptible to CPFX similarly to carbapenems and the MIC90 values of CPFX were in the range from < or = 0.063 to 2 micrograms/ml against strains except Stenotrophomonas maltophilia and Burkholderia cepacia. Pseudomonas aeruginosa was most susceptible to CPFX among the antibacterial drugs examined and the MIC90 was 2 micrograms/ml. CPFX also showed the lowest MIC90 value (0.5 microgram/ml) against beta-lactam-resistant P. aeruginosa among the drugs examined. When extended-spectrum beta-lactamase (ESBL) production and class B beta-lactamase production were examined in 439 strains of Enterobacteriaceae and 168 strains of glucose non-fermentative bacteria out of the Gram-negative bacteria collected this time, 3 strains (0.49%) producing ESBL and 7 strains (1.15%) producing class B beta-lactamase were found. The MIC range of CPFX to these 10 strains was between < or = 0.063 to 8 micrograms/ml and 5 strains among those showed susceptibilities (MIC of CPFX: 1 microgram/ml) based on the NCCLS breakpoint. CPFX also showed a satisfactory result concerning susceptibilities of major causal bacteria based on the report of the committee of Japan Society of Chemotherapy on the standard method for determination of susceptibility to antimicrobial agents, the breakpoint of pneumonia. Furthermore, susceptibilities of various bacteria isolated clinically from patients with severe infections this time did not differ much from the result of the nationwide surveillance which we conducted in 1997. Thus, it was concluded that the antimicrobial activity of CPFX was maintained in the post-marketing surveillance for its parenteral preparation.

Adolescent↗