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PubMed1981

The effect of polyamines on the poly(adenylic acid)-induced inhibition of ribonuclease activity.

Segments of poly(A) at the 3'-termini of 5 S rRNA inhibit the activities of ribonucleases from Citrobacter, Enterobacter, bovine pancreas, human spleen and human plasma. Certain polyamines, or compounds containing polyamine substructures, mediate reversal of this inhibition. Effective compounds contain three amino groups, at least two of which are charged and are separated from the others by no less than three carbon atoms. Spermidine and 9-aminoacridines, which contain substituted propyl- or butylamino moieties at the 9-amino position and which bear two positive charges per molecule, are efficacious at low concentrations (5 microM). A decrease in effectiveness is associated with the removal of one aromatic ring from the 9-aminoacridines. However, the resulting 4-aminoquinolines, unlike the acridines, do not inhibit enzyme activity when present in concentrations above 30 microM. Relocating the diamino side chain from the 4- to the 8-position of the quinoline nucleus causes a decrease in charge density to +1, with the result that such compounds are ineffective. The orders of polyamine efficacy of reversal of inhibition were similar for enzymes from Citrobacter, bovine pancreas, and human plasma, and paralleled the order of binding of polyamines to either poly(A) or 5 S rRNA. This was not the case with Enterobacter and human spleen RNAases, indicating that the identity of the most effective polyamines depends on the RNAase studied. The combination of variable 3'-terminal poly(A) segment length and polyamine identity and concentration constitutes a system by which RNAase activities, and, therefore, substrate-degradation rates, may be easily varied.

Animals↗
PubMed2003

Anaerobic cocci populating the deep tissues of chronic wounds impair cellular wound healing responses in vitro.

BACKGROUND: Anaerobic cocci are estimated to be present in the deep tissues of over 50% of chronic skin wounds. While the part they play in the chronicity of these wounds is uninvestigated, anaerobic cocci have previously been shown to be involved in other chronic inflammatory human conditions. METHODS: In this study the anaerobic microflora of the deep tissues of 18 patients with refractory chronic venous leg ulcers (mean age 80.3 years; mean duration > 24 months) was characterized using strict anaerobic culture conditions. The effect of the anaerobic organisms isolated from these tissues on extracellular matrix (ECM) proteolysis and cellular wound healing responses was studied using in vitro models. RESULTS: Anaerobic organisms were present in the deep tissues of 14 of 18 wounds and were principally Peptostreptococcus spp. The effects of three Peptostreptococcus spp. isolated from these wounds (P. magnus, P. vaginalis and P. asaccharolyticus) on cellular wound healing responses were compared with those of two pathogenic organisms also isolated from these wounds (Pseudomonas aeruginosa and Citrobacter diversus). While the direct ECM proteolytic activity exhibited by the Peptostreptococcus spp. was limited, they did significantly inhibit both fibroblast and keratinocyte proliferation, but only at high concentrations. However, at lower concentrations peptostreptococcal supernatants profoundly inhibited keratinocyte wound repopulation and endothelial tubule formation. The magnitude of these effects varied between strains and they were distinct from those demonstrated by Pseudomonas aeruginosa and Citrobacter diversus. CONCLUSIONS: These studies confirm the importance of anaerobic organisms in chronic wounds and demonstrate an indirect, strain-specific mechanism by which these microorganisms may play a part in mediating the chronicity of these wounds.

Aged↗
PubMed2003

Dietary pectin and calcium inhibit colonic proliferation in vivo by differing mechanisms.

Diet plays an important role in promoting and/or preventing colon cancer; however, the effects of specific nutrients remain uncertain because of the difficulties in correlating epidemiological and basic observations. Transmissible murine colonic hyperplasia (TMCH) induced by Citrobacter rodentium, causes significant hyperproliferation and hyperplasia in the mouse distal colon and increases the risk of subsequent neoplasia. We have recently shown that TMCH is associated with an increased abundance of cellular beta-catenin and its nuclear translocation coupled with up-regulation of its downstream targets, c-myc and cyclin D1. In this study, we examined the effects of two putatively protective nutrients, calcium and soluble fibre pectin, on molecular events linked to proliferation in the colonic epithelium during TMCH. Dietary intervention incorporating changes in calcium [high (1.0%) and low (0.1%)] and alterations in fibre content (6% pectin and fibre-free) were compared with the standard AIN-93 diet (0.5% calcium, 5% cellulose), followed by histomorphometry and immunochemical assessment of potential oncogenes. Dietary interventions did not alter the time course of Citrobacter infection. Both 1.0% calcium and 6% pectin diet inhibited increases in proliferation and crypt length typically seen in TMCH. Neither the low calcium nor fibre-free diets had significant effect. Pectin diet blocked increases in cellular beta-catenin, cyclin D1 and c-myc levels associated with TMCH by 70%, whereas neither high nor low calcium diet had significant effect on these molecules. Diets supplemented with either calcium or pectin therefore, exert anti-proliferative effects in mouse distal colon involving different molecular pathways. TMCH is thus a diet-sensitive model for examining the effect of specific nutrients on molecular characteristics of the pre-neoplastic colonic epithelium.

Adhesins, Bacterial↗
PubMed1995

The relationship between antecedent antibiotic use and resistance to extended-spectrum cephalosporins in group I beta-lactamase-producing organisms.

Gram-negative pathogens are increasingly resistant to extended-spectrum cephalosporins (ESCs). Using a prospective, case-controlled observational study, we examined the prevalence and the risk factors for development of resistance to ESCs in group I beta-lactamase-producing organisms. Of the 386 isolates of Enterobacter species, Pseudomonas aeruginosa, Citrobacter species, and Serratia marsescens from 340 consecutive patients, 70 (18.1%) were resistant to ESCs; the highest rates of resistance were found among Citrobacter freundii (40.9%), Enterobacter cloacae (31.1%), and Enterobacter aerogenes isolates (18.9%). Patients' prior antibiotic use and the mean number of antibiotics used were significantly greater in association with resistant vs. susceptible isolates. Resistance was associated with prior use of ceftizoxime or cefotaxime (P = .008), ceftazidime (P = .004), and piperacillin (P = .001). Other antibiotics were not associated with resistance. Resistance was less frequent in patients receiving ESCs and an aminoglycoside. We conclude that prior use of ESCs is associated with the isolation of resistant group I beta-lactamase-producing organisms. Concomitant use of an aminoglycoside may decrease this risk.

Adult↗
PubMedDate not supplied

Induction/inhibition of chromosomal beta-lactamases by beta-lactamase inhibitors.

Many species of gram-negative bacteria produce chromosomal beta-lactamases that can be induced to high-level expression by exposure to beta-lactam antibiotics. Fifty-four strains of Escherichia coli, Enterobacter, Proteus, Citrobacter, and Morganella were examined for beta-lactamase inducibility by clavulanic acid, sulbactam, YTR 830, ampicillin, and cefoxitin. Cefoxitin proved to be the most potent inducer, affecting most of the strains of Enterobacter and Morganella. Clavulanic acid induced 30% of all strains studied. Sulbactam and YTR 830 did not induce measurable levels of beta-lactamases. Inhibition of some chromosomal beta-lactamases by sulbactam and YTR 830 was demonstrated, whereas inhibitory activity by clavulanic acid was found only in Proteus and Citrobacter.

Ampicillin↗
PubMed1987

Dynamics of ceftazidime-pefloxacin interaction shown by a new killing curve-chequerboard method.

Since in-vitro methods for studying drug interactions are difficult to evaluate and different results occur with the chequerboard (isobolograms-FIC index) and killing curve methods, a new approach associating these two methods was used to study the ceftazidime-pefloxacin interaction. In 64 tubes in a chequerboard pattern, viable bacteria were counted at 0, 2.5, 5 and 24 h, by a microdilution method and a multiple inoculator replicating method. The bacterial inoculum consisted of 5 X 10(6)-10(7) cfu/ml. Twelve strains belonging to six genera were tested: Acinetobacter, Citrobacter, Enterobacter, Klebsiella, Serratia and Pseudomonas. During the first 5 h no antagonism was noted, but few differences in viable count equal to or greater than 2 log10 were observed. The results of the drug interaction were equivalent to those of the more rapid bactericidal antibiotic concentrations (ceftazidime or pefloxacin). At 24 h, synergy was observed: ceftazidime prevented the late regrowth noted with pefloxacin, but with Citrobacter spp. regrowth was also observed with ceftazidime and none of the combinations were bactericidal.

Acinetobacter↗
PubMed1976

Immunological relationships of bacterial L-asparaginases.

Rabbit antisera against L-asparaginase preparations from Escherichia coli, Erwinia carotovora, Citrobacter sp. and Chromobacterium violaceum showed on immunoelectrophoresis that only the enzymes from E. coli and Citrobacter are immunologically related. Purified preparations had to be used to determine the immunological cross-reactions. Immunoelectrophoresis at different pH values yielded the zero mobility points of the enzymes. The activity of the Er. carotovora preparation was enhanced up to fourfold by homologous antiserum but not by normal sera. Heterologous antisera also enhanced, but only at a higher concentration. Less enhancement was observed for the other enzymes with antisera as well as with bovine serum albumin. Inhibition was not observed.

Antibodies, Bacterial↗
PubMed1995

Development and evaluation of two novel oligonucleotide probes based on 16S rRNA sequence for the identification of Salmonella in foods.

DNA sequence in the V3 to V6 region of the 16S rRNA gene of Salmonella enteritidis was determined. By comparison of this sequence with those of Escherichia coli and Proteus vulgaris obtained from GenBank/EMBL database, three oligonucleotides termed as 16S I, 16S II and 16S III were synthesized. Hybridization of these oligonucleotides with 325 Salmonella isolates and some non-Salmonella isolates including the Salmonella closely related species of the family of Enterobacteriaceae showed that 16S II could not be used as a Salmonella specific-probe. 16S I and 16S III hybridized with all the Salmonella isolates tested, the former also hybridizing with Citrobacter spp. and the latter hybridizing with Klebsiella pneumoniae as well as Serratia marcescens. Since enrichment of the target cells in food samples was usually required prior to the DNA hybridization assay, the interference from those non-Salmonella isolates could be prevented by enrichment by culturing in lactose-combined tetrathionate (CTET) broth followed by Gram-negative (GN) broth at 37 degrees C and/or 43 degrees C. Such a culture step could inhibit the growth of Klebsiella spp., Ser. marcescens and/or Citrobacter spp. and allowed the specific detection of Salmonella.

Base Sequence↗
PubMed1975

Heterogeneity of lipopolysaccharides. Analysis of polysaccharide chain lengths by sodium dodecylsulfate-polyacrylamide gel electrophoresis.

Lipopolysaccharide preparations from R(rough) Escherichia coli O8-,SR(semirough) Salmonella typhimurium and S (smooth) strains E. coli O8 and Citrobacter 396 were disintegrated with sodium dodecylsulfate and subjected to polyacrylamide gel electrophoresis in the presence of 1% sodium dodecylsulfate. The results obtained were compared with those obtained from the same lipopolysaccharide preparations by degradation analysis. In dodecylsulfate gel electrophoresis the lipopolysaccharide preparation from the E. coli R mutant and the S. typhimurium SR mutant showed one band each (R-and SR-band, respectively) with different electrophoretic mobilities. The lipopolysaccharide preparations from the E. coli O8-strain exhibited two bands, one of which had the same electrophoretic mobility as the R-band and the other was identified as S-band. The lipopolysaccharide preparation from the Citrobacter 396-S-strain exhibited four bands: one R-band, one SR-band and two S-bands. The results showed that wild-type S strains contain more than one type of lipopolysaccharide. They differ in the length of their O-specific polysaccharide chains. The lipid A content of the different lipopolysaccharide was expressed in their electrophoretic mobilities.

Citrobacter↗
PubMed1991

Modulation of the intestinal flora of mice by parenteral treatment with broad-spectrum cephalosporins.

A study was performed to determine the effect of parenteral treatment with four broad-spectrum cephalosporins (cefoperazone, ceftriaxone, ceftazidime, and cefepime) on the number of aerobic gram-negative rods and on the outgrowth of Candida albicans and a multiresistant strain of Citrobacter freundii in the feces of mice. The estimated fractions of a parenteral dose that were excreted into the gastrointestinal tract were 0.37 for cefoperazone, 0.11 for ceftriaxone, 0.03 for ceftazidime, and 0.002 for cefepime. All four cephalosporins significantly decreased the number of aerobic gram-negative rods in the feces, and virtually all gram-negative rods were eliminated at high doses of cefoperazone, ceftazidime, and ceftriaxone. Furthermore, at high doses these three compounds led to a significant increase of the outgrowth of resistant Citrobacter freundii. The outgrowth of Candida albicans was increased at high doses of cefoperazone and ceftriaxone, whereas ceftazidime and cefepime did not have this effect. The most profound changes in the gastrointestinal ecology were observed during treatment with high doses of cefoperazone. The results suggest that the colonization resistance of the gastrointestinal tract can be substantially decreased by parenteral treatment with cefoperazone and, to a lesser extent, with ceftriaxone and ceftazidime.

Animals↗
PubMed1997

Characterization of the 6'-N-aminoglycoside acetyltransferase gene aac(6')-Im [corrected] associated with a sulI-type integron.

The amikacin resistance gene aac(6')-Im [corrected] from Citrobacter freundii Cf155 encoding an aminoglycoside 6'-N-acetyltransferase was characterized. The gene was identified as a coding sequence of 521 bp located down-stream from the 5' conserved segment of an integron. The sequence of this aac(6')-Im [corrected] gene corresponded to a protein of 173 amino acids which possessed 64.2% identity in a 165-amino-acid overlap with the aac(6')-Ia gene product (F.C. Tenover, D. Filpula, K.L. Phillips, and J. J. Plorde, J. Bacteriol. 170:471-473, 1988). By using PCR, the aac(6')-Im [corrected] gene could be detected in 8 of 86 gram-negative clinical isolates from two Belgian hospitals, including isolates of Citrobacter, Klebsiella spp., and Escherichia coli. PCR mapping of the aac(6')-Im [corrected] gene environment in these isolates indicated that the gene was located within a sulI-type integron; the insert region is 1,700 bases long and includes two genes cassettes, the second being ant (3")-Ib.

Acetyltransferases↗
PubMed1993

Copper-resistant enteric bacteria from United Kingdom and Australian piggeries.

Thirty-three enteric isolates from Australian (Escherichia coli only) and United Kingdom (U.K.) (Salmonella sp., Citrobacter spp., and E. coli) piggeries were characterized with respect to their copper resistance. The copper resistance phenotypes of four new Australian E. coli isolates were comparable with that of the previously studied E. coli K-12 strain ED8739(pRJ1004), in that the resistance level in rich media was high (up to 18 mM CuSO4) and resistance was inducible. Copper resistance was transferable by conjugation from the new Australian isolates to E. coli K-12 recipients. DNA similarity between the new Australian isolates and the pco copper resistance determinant located on plasmid pRJ1004 was strong as measured by DNA-DNA hybridization; however, the copper resistance plasmids were nonidentical as indicated by the presence of restriction fragment length polymorphisms between the plasmids. DNA-DNA hybridization and polymerase chain reaction analysis demonstrated DNA homology between the pco determinant and DNA from the U.K.E. coli, Salmonella sp., and Citrobacter freundii isolates. However, the copper resistance level and inducibility were variable among the U.K. strains. Of the U.K. E. coli isolates, 1 demonstrated a high level of copper resistance, 4 exhibited intermediate resistance, and 16 showed a low level of copper resistance; all of these resistances were expressed constitutively. A single U.K. C. freundii isolate, had a high level of copper resistance, inducible by subtoxic levels of copper. Transconjugants from one E. coli and one C. freundii donor, with E. coli K-12 strain UB1637 as a recipient, showed copper resistance levels and inducibility of resistance which differed from that expressed from plasmid pRJ1004.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Husbandry↗
PubMed1980

Evaluation of a new assay for Vi antibody in chronic carriers of Salmonella typhi.

The assay for serum antibody to the Salmonella typhi capsular polysaccharide (Vi) antigen has recently been revised because of the availability of a purified, highly polymerized Vi antigen. We compared this revised Vi antibody assay to the traditional one for potential usefulness in the surveillance of chronic enteric carriers of S. typhi. The purified Vi antigen of Citrobacter freundii was incorporated into a passive hemagglutination assay for serum Vi antibody; the standard Vi antibody assay was also a hemagglutination assay that employed as the Vi antigen a crude extract of Citrobacter (Ballerup O group 29). As determined by the revised assay, Vi antibody was found in the sera of 22 (71%) of 31 current typhoid carriers, none of 6 resolved carriers, and none of 22 control subjects. According to the traditional assay, Vi antibody was present in 23 of those current carriers (74%), 1 of the resolved carriers (17%), and 4 of the control subjects (18%). The rate of false-positive Vi antibody tests among resolved carriers and control subjects was less with the revised assay (P < 0.05). Successful antimicrobial therapy resulted in a reversion to seronegativity within 1 year in 8 of 10 Vipositive carriers according to the revised assay, but in only 3 of 11 according to the standard assay (P < 0.05). During a 2-year period of observation, 15 (94%) of 16 current typhoid carriers had at least one positive purified Vi antibody test; among 12 of those patients with Vi titers of 1:40 or greater, 9 (75%) were continuously Vi positive. Thus, the revised Vi antibody assay is more specific and no less sensitive than the standard assay for the condition of current enteric carriage of S. typhi. This serological test could be of value in the surveillance of typhoid carriers by public health agencies.

Aged↗
PubMed1986

Effect of inoculum size on ampicillin and amoxycillin susceptibility determined by gas-liquid chromatography for members of the family Enterobacteriaceae.

Inoculum size had only a small effect on the results for ampicillin and amoxycillin susceptibility testing of Escherichia coli. In contrast, a difference in inoculum size from 10(6) to 10(8) CFU/ml profoundly affected the results for ampicillin and amoxycillin susceptibility testing of Proteus mirabilis, causing a change from susceptibility to complete resistance. These different effects of inoculum size were observed both when susceptibility was determined by the suppression of a characteristic metabolic product analyzed by head-space gas-liquid chromatography (HS-GLC) and when it was determined by MIC testing in broth. Inoculum size affected the results for ampicillin susceptibility of P. mirabilis determined concurrently with the rapid HS-GLC urine test, because 10(8) CFU/ml may occur in urine specimens. In the rapid test, significant numbers of Escherichia, Klebsiella, Citrobacter, Proteus, Morganella, and Providencia spp. in urine specimens are detected within 4 h by HS-GLC analysis for characteristic metabolic products in cultures. Most P. mirabilis in urine specimens appeared to be ampicillin resistant in the rapid HS-GLC test but were reported to be ampicillin susceptible in hospital laboratory agar dilution tests 2 days later. However, ampicillin susceptibility results for Escherichia, Klebsiella, and Citrobacter spp. agreed with hospital laboratory reports. It was concluded that reports of ampicillin susceptibility or resistance for the commonest cause of urinary tract infections, E. coli, within 4 h of receipt of the specimen would be clinically valuable and that a provisional report of ampicillin resistance for P. mirabilis would not lead to ineffective therapy.

Amoxicillin↗
PubMedDate not supplied

The catalytic mechanism of tyrosine phenol-lyase from Erwinia herbicola: the effect of substrate structure on pH-dependence of kinetic parameters in the reactions with ring-substituted tyrosines.

Apparently homogeneous tyrosine phenol-lyase (TPL) from Erwinia herbicola has been prepared by a new method. The pH-dependencies of the main kinetic parameters for the reactions of Erwinia TPL with tyrosine, 2-fluorotyrosine, 3-fluorotyrosine, 2-chlorotyrosine, and 3,4-dihydroxyphenylalanine (DOPA) have been studied. The pattern of pH-dependence of V(max) depends on the nature of the substituent in the aromatic ring. For the substrates bearing small substituents (H, 2-F, 3-F) V(max) values were found to be pH-independent. For 2-chlorotyrosine and DOPA V(max) decreased at lower pH, the effect being described by equation with one pKa. Generally two bases are reflected in the pH dependence of V(max)/Km. The first base, probably is responsible for the abstraction of alpha-proton, while the second one, interacts with the phenolic hydroxyl at the stage of binding. The reaction of TPL with DOPA differs from the reactions with other tyrosines by the requirement of an additional base which is reflected in the pH-profiles of both V(max) and V(max)/Km. For the reaction of TPL from Citrobacter intermedius with DOPA only V(max)/Km values could be determined. The activity of Citrobacter enzyme towards DOPA is considerably less than that of E. herbicola enzyme, and its maximal value is attained at higher pH.

Ammonium Sulfate↗
PubMed2006

[Transference of extended-spectrum beta-lactamases from nosocomial strains of Klebsiella pneumoniae to other species of Enterobacteriaceae].

BACKGROUND: Klebsiella pneumoniae is an important pathogenic bacterium, frequently isolated from nosocomial samples, that exhibits wide antimicrobial resistance profiles, including third generation cephalosporins (3GC), aminoglycosides and quinolones. The resistance to 3GC is mainly due to the synthesis of extended spectrum beta lactamases (ESBL), encoded by conjugative plasmids. AIM: To investigate the potential transference of resistance to 3GC from nosocomial strains of K. pneumoniae to other clinical strains of various species of Enterobacteriaceae. MATERIAL AND METHODS: The mating experiments were carried out in liquid media and three nosocomial strains of K. pneumoniae were used as donors. These strains were ESBL-producers and resistant to, at least, one of the 3GC assayed. One strain of Citrobacter freundii, Salmonella typhimurium, Serratia marcescens and Escherichia coli, isolated from clinical specimens, were used as recipients. The presence of bla genes was investigated by PCR. RESULTS: The three nosocomial strains of K. pneumoniae were able to transfer the resistance to 3GC and the genes encoding the ESBL to the susceptible recipient strains of enterobacteria. The frequency of transference was as high as 3.2 x 10-2 transconjugants/recipient cell when the strain of Citrobacter freundii was used as recipient. All transconjugants exhibited high level of resistance to the 3GC assayed. CONCLUSIONS: Strains of K. pneumoniae isolated from Chilean hospitals are able to disseminate the ESBL genes to clinical strains of others species of Enterobacteriaaceae.

Anti-Bacterial Agents↗
PubMed1976

[Identification of conditionally pathogenic enterobacteria in laboratory practice in the diagnosis of acute intestinal diseases].

Identification of 361 cultures isolated from patients suffering from various acute intestinal diseasesand from persons who had sustained them, as well as from contacts and persons examined prophylactically with the use of various biochemical tests showed that ty their taxonomic properties the cultures were referred to conditionally-pathogenic representatives of Enterobacteriaceae of the corresponding genera:Citrobacter, Hafnia, Klebsiella, Proteus, Providencia. Serological typing of the strains of bacteria of the Citrobacter pointed to the most frequent circulation of the strains of the serological groups 04, 01, 03, 013, 05, 022, 08; among these groups 04, encountered among all the categories under study, prevailed. At the current stage of identification of conditionally pathogenic enterobacteria in practical laboratories it is of expedience to use in the diagnosis of intestinal diseases the serological typing along with a complex from several additional biochemical tests.

Citrobacter↗
PubMed2002

[Post-marketing surveillance of antibacterial activities of cefozopran against various clinical isolates--II. Gram-negative bacteria].

As a post-marketing surveillance, the in vitro antibacterial activities of cefozopran (CZOP), an agent of cephems, against various clinical isolates were yearly evaluated and compared with those of other cephems, oxacephems, penicillins, monobactams, and carbapenems. Changes in CZOP susceptibility for the bacteria were also evaluated with the bacterial resistance ratio calculated with the breakpoint MIC. Twenty-five species (3,362 strains) of Gram-negative bacteria were isolated from the clinical materials annually collected from 1996 to 2000, and consisted of Moraxella (Branhamella) catarrhalis (n = 136), Haemophilus influenzae (n = 289), Escherichia coli (n = 276), Klebsiella pneumoniae (n = 192), Klebsiella oxytoca (n = 157), Enterobacter cloacae (n = 189), Enterobacter aerogenes (n = 93), Serratia marcescens (n = 172), Serratia liquefaciens (n = 24), Citrobacter freundii (n = 177), Citrobacter koseri (n = 70), Proteus mirabilis (n = 113), Proteus vulgaris (n = 89), Morganella morganii (n = 116), Providencia spp. (n = 41), Pseudomonas aeruginosa (n = 290), Pseudomonas fluorescens (n = 56), Pseudomonas putida (n = 63), Acinetobacter baumannii (n = 146), Acinetobacter lwoffii (n = 34), Burkholderia cepacia (n = 101), Stenotrophomonas maltophilia (n = 169), Bacteroides fragilis group (n = 196), and Prevotella/Porphyromonas (n = 173). An antibacterial activity of CZOP against E. coli, K. pneumoniae, K. oxytoca, and S. marcescens was potent and consistent with or more preferable than the study results obtained until the new drug application approval. MIC90 of CZOP against M.(B.) catarrhalis, C. koseri, and P. aeruginosa was not considerably changed and consistent with the study results obtained until the new drug application approval. MIC90 of CZOP against E. cloacae, E. aerogenes, and P. mirabilis increased year by year. The increase in MIC90 of CZOP against E. aerogenes and P. mirabilis, however, was not considered to be an obvious decline in susceptibility. In contract, the susceptibility of E. cloacae to CZOP was suspected to be decreasing because this species showed 20.6% resistance to CZOP. MIC90 of CZOP against C. freundii was variably changed or not one-sidedly, but was higher than the values obtained until the new drug application approval. Additionally, MIC90 of CZOP against H. influenzae was stable during 5 years except being higher in 1999, and, as a whole, was a little higher than the values obtained until the new drug application approval. An antibacterial activity of CZOP against P. fluorescens, P. putida, B. cepacia, S. maltophilia, B. fragilis group, and Prevotella/Porphyromonas was weak like the other cephems. Changes in MIC90 of CZOP against the other bacteria were 2 tubes or more through 5-year study period, but did not tend towards a unilateral direction as meaning a decline in susceptibility.

Acinetobacter↗