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Analysis of AmpC beta-lactamase expression and sequence in biochemically atypical ceftazidime-resistant Enterobacteriaceae from paediatric patients.

OBJECTIVES: To analyse the variation of ampC beta-lactamase gene sequence and expression in biochemically atypical Enterobacteriaceae isolates, and to identify them definitively. METHODS: beta-Lactamase gene-containing recombinant plasmids transformed into Escherichia coli were selected using ampicillin. PCR analysis was used to locate specific ampC and 16S rRNA genes, and the amplicons were sequenced. Random amplified polymorphic DNA PCR was used to group isolates and API 20E biochemical profiling was used to identify them putatively. RESULTS: Of 50 ceftazidime-resistant clinical Enterobacteriaceae isolates, 36 were identified (>95% confidence)-using API 20E test strips-as being organisms known to express inducible class C beta-lactamases (Citrobacter freundii, Enterobacter cloacae, Morganella morganii or Hafnia alvei). The rest were biochemically atypical. Of these, isolate I113, putatively identified as E. coli, possesses a chromosomally encoded ampC which differs by 15% from C. freundii OS60 ampC and by >30% from E. coli ampC. A related ampC gene was found in another seven of the atypical isolates. The use of various identification methods, including ampC sequence analysis, revealed that these I113-like ampC-positive isolates represent Citrobacter murliniae and Citrobacter youngae. CONCLUSIONS: We report sequences for two new Citrobacter spp. ampC genes, and provide evidence that ampC sequencing is a discriminatory method for identifying atypical Citrobacter spp. isolates.

Bacterial Proteins↗

[Persistense of mono- and associated cultures of conditionally pathogenic enterobacteria].

The comparative study of adhesive, hemolytic, DNA-ase, lecithinase, antilysozymic, anticomplementary activities of mono- and associated cultures of 57 Enterobacter spp., 61 Citrobacter spp. and 55 Serratia spp. strains, isolated from patients with pyoinflammatory, intestinal and urological diseases is carried out. Different variations of cocultivated bacteria including Enterobacter and Citrobacter, Enterobacter and Serratia, Citrobacter and Serratia are used. It was shown, that cocultivated Enterobacter, Citrobacter and Serratia bacteria increased the persistent properties of mixt cultures.

Animals↗

The microbiology of transmissible murine colonic hyperplasia.

The relationship of Citrobacter freundii (4280) to the development of colonic hyperplasia in mice was investigated. The number of Citrobacter freundii (4280) in the descending colon were quantitated at intervals following experimental inoculation, and findings were correlated with previously reported histological and ultrastructural findings. Citrobacter freundii (4280) was a transient infection, lasting 2-3 weeks, after which time mice no longer harbored the organism. Neomycin sulfate and tetracycline hydrochloride, when administered in the drinking water, were useful in the prevention of infection as well as ablation of established infection. The presence of Citrobacter freundii (4280) for as little as 2 days was sufficient stimulus to result in detectable mucosal hyperplasia. The longer the bacterium was present, through 10 days, the greater the hyperplasia.

Animals↗

In vitro activity and beta-lactamase stability of LJC 10,627.

The in vitro activity of LJC 10,627, a new carbapenem, was compared with those of imipenem, cefotaxime, ceftazidime, and gentamicin. LJC 10,627 inhibited 90% of Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter cloacae, Hafnia alvei, Citrobacter freundii, Citrobacter diversus, Proteus mirabilis, Morganella morganii, Proteus rettgeri, Serratia marcescens, Pseudomonas cepacia, salmonellae, shigellae, aeromonas, and yersiniae at less than or equal to 2 micrograms/ml. Haemophilus influenzae was inhibited by 0.5 microgram/ml, and moraxellae were inhibited by 0.12 microgram/ml. LJC 10,627 was twofold more active than imipenem against aerobic gram-negative organisms and inhibited ceftazidime-, cefotaxime-, and gentamicin-resistant members of the genera Klebsiella, Enterobacter, Citrobacter, and Serratia at less than or equal to 2 micrograms/ml. Xanthomonas maltophilia strains were resistant to the drug. Imipenem was two- to fourfold more active than LJC 10,627 against Staphylococcus aureus and Staphylococcus epidermidis. LJC 10,627 did not inhibit most methicillin-resistant Staphylococcus aureus or methicillin-resistant Staphylococcus epidermidis strains. LJC 10,627 inhibited Streptococcus pyogenes and Streptococcus pneumoniae at 0.06 and 0.12 microgram/ml, respectively. Bacteroides fragilis and other Bacteroides spp. were inhibited by 0.5 microgram of LJC 10,627 per ml. Serum (50%) did not affect the MICs. LJC 10,627 was not hydrolyzed by plasmid-mediated beta-lactamases of Bush types 2b, 2b', TEM-1, TEM-2, TEM-3, TEM-5, TEM-7, TEM-9, and SHV-1; the chromosomal beta-lactamases of Bush type 1; P-99; a Morganella enzyme; or a Citrobacter freundii enzyme. The Bush type 2c and 2d enzymes OXA-1, OXA-2, PSE-1, PSE-2, and PSE-4 did not hydrolyze LJC 10,627, nor did the beta-lactamases of Staphylococcus aureus, Moraxella spp., Bacteroides fragilis, and Proteus vulgaris. The beta-lactamase of Xanthomonas hydrolyzed LJC 10,627, albeit at approximately one-third the rate that imipenem was hydrolyzed.

Carbapenems↗

Klebsiella biotypes among coliforms isolated from forest environments and farm produce.

Samples of water, soil, needles, and bark were collected from three different forest environments and from a pulp and paper mill. In addition, samples of fresh produce were obtained from a local supermarket. All samples were examined for total and fecal coliforms. The counts obtained from the forestrelated samples did not correlate with sample type or location. When 123 isolates were identified biochemically, 71% were Klebsiella, 19% Enterobacter, 8% Citrobacter, and 2% Escherichia. All the Citrobacter, 75% of the Enterobacter, and 65% of the Klebsiella were negative for growth in elevated coliform (EC) broth. All the Escherichia were EC positive. The counts obtained from the fresh produce were generally higher than the forest counts, but the distribution of biotypes was similar. Of the 146 isolates examined 64% were Klebsiella, 14% were Escherichia, 14% were Enterobacter, and 8% were Citrobacter. All the Enterobacter and Citrobacter were EC negative, whereas 25% of the Klebesiella and 80% of the Escherichia were EC positive.

Bacteriological Techniques↗

Production of cellulose and curli fimbriae by members of the family Enterobacteriaceae isolated from the human gastrointestinal tract.

Citrobacter spp., Enterobacter spp., and Klebsiella spp. isolated from the human gut were investigated for the biosynthesis of cellulose and curli fimbriae (csg). While Citrobacter spp. produced curli fimbriae and cellulose and Enterobacter spp. produced cellulose with various temperature-regulatory programs, Klebsiella spp. did not show pronounced expression of those extracellular matrix components. Investigation of multicellular behavior in two Citrobacter species and Enterobacter sakazakii showed an extracellular matrix, cell clumping, pellicle formation, and biofilm formation associated with the expression of cellulose and curli fimbriae. In those three strains, the csgD-csgBA region and the cellulose synthase gene bcsA were conserved. PCR screening for the presence of csgD, csgA and bcsA revealed that besides Klebsiella pneumoniae and Klebsiella oxytoca, all species investigated harbored the genetic information for expression of curli fimbriae and cellulose. Since Citrobacter spp., Enterobacter spp., and Klebsiella spp. are frequently found to cause biofilm-related infections such as catheter-associated urinary tract infections, the human gut could serve as a reservoir for dissemination of biofilm-forming isolates.

Amino Acid Sequence↗

Resistance patterns among selective Gram-negative bacilli from an intensive care unit in Trinidad, West Indies.

OBJECTIVE: To determine the prevalence of antimicrobial resistance among gram-negative aerobic bacteria isolated from infected patients on the intensive care unit (ICU) and the outcome of infected patients. METHODS: Over a 5-year period (January 1998 to December 2002), all gram-negative aerobic bacteria (GNB) consecutively isolated from infected ICU patients at General Hospital, San Fernando, Trinidad and Tobago, West Indies. were tested for susceptibility to 10 commonly prescribed antimicrobial agents. Bacterial strains were identified according to standard microbiological procedures. The antimicrobial agents used and the amounts consumed by patients on the ICU were obtained from the hospital pharmacy records. Hospital discharges and deaths due to infectious complications were obtained from the medical records office and the ICU. RESULTS: During the study period, there were 1160 admissions to the ICU. From this, 530 (45.7%) were suspected episodes of nosocomial infection and 445 (84%) were culture positive for GNB. Sputum, urine and blood accounted for approximately 85% of isolates. Pseudomonas aeruginosa (P. aeruginosa), Klebsiella pneumoniae (K. pneumoniae), Citrobacter spp and Enterobacter spp were the predominant isolates from sputum, while from urine; it was P. aeruginosa and K. pneumoniae. The major isolate from bloodstream infection on the ICU was Citrobacter spp. Of the 10 antimicrobial agents, the least effective was ampicillin that showed 87.8% resistance, while the most effective against GNB were imipenem (94.2%), ciprofloxacin (93.9%) and piperacillin-tazobactam (88.5%). The most common isolate was P. aeruginosa which is sensitive to >82% of the antimicrobials. Antimicrobial consumption was 2282 grams and the most frequently prescribed drugs were ampicillin, cefuroxime and amoxicillin-clavulanic acid, with consumption of the beta-lactam antimicrobials being 87.3% of the total. There were 280 (24.1%) deaths on the ICU during the study period and 42.9% (120 of 280) were said to be due to, or associated with overall hospital-acquired infectious complications. Mortality associated with GNB infection was approximately 33%. All fatal cases were associated with pneumonia and bloodstream infections. The predominant organisms were Citrobacter spp, Enterobacter spp, Acinetobacter spp and P. aeruginosa, with Citrobacter spp associated with both pulmonary and bloodstream fatalities. CONCLUSION: In general, the isolates were relatively antimicrobial susceptible. Imipenem, ciprofloxacin and piperacillin-tazobactam were found good empiric choices for treatment of most GNB infection in the ICU. The study showed that resistance among ICU pathogens depended on the site of infection and that increased drug consumption of any antimicrobial agent may lead to increase resistance to those drugs. The need for policies governing the prudent use of antimicrobial agents cannot be overemphasized. Many endeavors aimed at introducing an antibiotic policy have encountered repeated failure and attempts at rational prescribing through educational programs have met with limited success. Hope is seen however, in proper implementation of infection control procedures aimed specifically to curtail lateral transmission of resistant organisms.

Drug Resistance, Bacterial↗

[Evaluation of the usefulness of tests for production of Beta-D-glucuronidase and propylene glycol utilization for the differentiation of enterobacteriaceae rods].

The aim of the study was to inquire about the diagnostic usefulness of determining the activity of glucuronidase and utilisation of propylene glycol in Enterobacteriaceae rods. The study included 1511 strains: 411- E. coli, 278 - Klebsiella, 231 - Salmonella, 159 - Yersinia, 97 - Citrobacter, 75 - Shigella and 260 strains representing 6 other kinds of enteric rods. Determination was performed in a liquid medium containing in 1 ml 25 mcg MUG and 100 mcg ONPG. Propylene glycol (PG) utilisation was observed in peptone water with 2% of the substrate and with the Andrade indicator. In comparative tests Rambach commercial medium and MacConkey agar from the Fluorocult series were used. In the test with MUG a positive result was obtained from 81.8% E. coli, 65% - Shigella and 13% - Salmonella subgenus I. Only exceptionally was this test positive with Providencia, Enterobacter and Yersinia strains (1-5%) but negative with Citrobacter, Klebsiella, Serratia, Hafnia, Proteus and Morganella strains. Glucuronidase production is not sufficiently characteristic of E. coli strains isolated from humans to be the only basis for the preliminary differentiation of these rods from other Enterobacteriaceae. The test with ONPG was positive from 95-100% E. coli, Yersinia, Citrobacter, Klebsiella, Enterobacter and Hafnia strains; 61% - Shigella, 9% - Salmonella and 3% - Providencia, but negative with Serratia, Proteus and Morganella strains. Propylene glycol was decomposed by 74% Salmonella strains of subgenus I, 65-94% - Klebsiella, Yersinia and Citrobacter. Shigella, Enterobacter, Serratia, Proteus, Providencia and Morganella rods did not decompose propylene glycol. Evidence that among strains non-decomposing propylene glycol were all the studied S. typhi, S. paratyphi A, S. paratyphi C, S. choleraesuis, S. virchow and S. gallinarum strains as well as a significant percentage of strains representing 8 other Salmonella serotypes frequently detected allows to believe that the use of activity against propylene glycol even simultaneously with the test for galactosidase as basis for the differentiation of Salmonella rods of subgenus I from other Enterobacteriaceae can lead to errors already at the onset of diagnostic procedure.

Bacterial Typing Techniques↗

The use of Escherichia coli bearing a phoN gene for the removal of uranium and nickel from aqueous flows.

A Citrobacter sp. originally isolated from metal-polluted soil accumulates heavy metals via metalphosphate deposition utilizing inorganic phosphate liberated via PhoN phosphatase activity. Further strain development was limited by the non-transformability of this environmental isolate. Recombinant Escherichia coli DH5 alpha bearing cloned phoN or the related phoC acquired metal-accumulating ability, which was compared with that of the Citrobacter sp. with respect to removal of uranyl ion (UO2(2+)) from dilute aqueous flows and its deposition in the form of polycrystalline hydrogen uranyl phosphate (HUO2PO4). Subsequently, HUO2PO4-laden cells removed Ni2+ from dilute aqueous flows via intercalation of Ni2+ into the HUO2PO4 lattice. Despite comparable acid phosphatase activity in all three strains, the E. coli DH5 alpha (phoN) construct was superior to Citrobacter N14 in both uranyl and nickel accumulation, while the E. coli DH5 alpha (phoC) construct was greatly inferior in both respects. Expression of phosphatase activity alone is not the only factor that permits efficient and prolonged metal phosphate accumulation, and the data highlight possible differences in the PhoN and PhoC phosphatases, which are otherwise considered to be related in many respects.

Biodegradation, Environmental↗

Do inert beta-lactamase inhibitors act as synergizers of beta-lactam antibiotics? Utility of boric and boronic acids.

Boric and boronic acids were used as inhibitors of beta-lactamases produced by two Citrobacter diversus strains and by one strain of Pseudomonas aeruginosa; all strains were clinical isolates. The beta-lactamases produced by the two Citrobacter diversus strains were inhibited by both borates and boronates, using cephazolin as substrate. The enzyme from Pseudomonas aeruginosa was inhibited only by boronates, using benzylpenicillin as substrate. These inhibitors were also used in combination with selected beta-lactams so as to determine if a synergism of antimicrobial activity occurred. All data reported in the present paper indicate that the minimum inhibitory concentration (MIC) values were lowered in the presence of these inhibitors for the two Citrobacter diversus strains. In the Pseudomonas aeruginosa strains the MIC values were not significantly altered, thus indicating the presence of a permeability barrier for 3-aminophenylboronic acid.

Anti-Bacterial Agents↗

Evaluation of the repliscan system for Enterobacteriaceae identification.

A total of 1,013 isolates of Enterobacteriaceae were identified in parallel by the Repliscan (Cathra International, Ontario, Canada) and API 20E (Analytab Products, Plainview, N.Y.) systems. There was a 62% agreement at the genus level between the two systems. Of the 38% discrepant results, Repliscan classified 22% as "biochemical pattern not on file," 8% as a multiple-genus group which included the API 20E identification, and 8% as a genus other than that designated by API 20E. Relative to the various genera, Repliscan agreed with API 20E as follows: Escherichia coli, 80%; Klebsiella spp., 76%; Citrobacter spp., 75%; Proteus spp., 69%; Providencia spp., 54%; Serratia spp., 49%; Enterobacter spp., 25%; Shigella spp., 4%; and Salmonella spp., 0%. Repliscan identified 35% of Enterobacter spp. isolates as Citrobacter spp., 91% of Shigella spp. isolates as a multiple-choice-genus group, and 67% of Salmonella spp. isolates as "biochemical pattern not on file." Repliscan agreed with API 20E at the species level as follows: E. coli, 80%; Klebsiella spp., 56%; Citrobacter spp., 66%; Proteus spp., 55%; Providencia spp., 46%; Serratia spp., 39%; Enterobacter spp., 18%; Shigella spp., 4%; and Salmonella spp., 0%. These findings indicate that the Repliscan system in its present stage of development does not reliably identify the Enterobacteriaceae.

Bacteriological Techniques↗

Direct detection of eae-positive bacteria in human and veterinary colorectal specimens by PCR.

A PCR test based on the amplification of an eae-specific sequence was designed and evaluated for its ability to directly detect homologous sequences in enteropathogenic Escherichia coli and Citrobacter spp. (amplification of eae open reading frame, 178 bp) in sections of the intestines of humans and animals with colonic lesions. Positive PCR results were observed with eae-positive reference strains of E. coli and Citrobacter rodentium (Citrobacter freundii biotype 4280). Known eae-negative reference strains of E. coli and other laboratory strains of enteric bacteria were negative by the amplification test. The sensitivity of the PCR for detection of eae-positive E. coli and C. rodentium was between 1 and 2 CFU. To detect these sequences directly from sections of fixed colon from human and veterinary sources, PCR conditions were modified by the addition of 0.1 mM 8-methoxypsoralen to eliminate extraneous bacterial DNA from the PCR amplification cocktail without added template. Sections of colon from three pigs experimentally affected with colon lesions due to enteropathogenic (attaching and effacing) E. coli were PCR positive for bacterial eae genome. Sections from control animals were negative. Sections of colon from one of 18 biopsies from confirmed AIDS patients and from 22 of 35 colorectal cancer patients were PCR positive for bacterial eae genome. The PCR test was a simple and quick method of detecting bacterial eae genome in human and veterinary clinical specimens. This method may remove the need for initial culture and detection of the gene by DNA probing from potential associated lesions. The clear relationship of bacteria containing the eae gene with colonic lesions in the pigs and mice indicates that a similar relationship is possible for human patients having similar lesions.

Acquired Immunodeficiency Syndrome↗

Interspecific plasmid transfer and modification of heat-stable enterotoxin expression by Klebsiella pneumoniae from infants with diarrhea.

We have previously described two heat-stable enterotoxins (ST) produced by Citrobacter freundii and by Klebsiella pneumoniae. To see whether transfer of toxigenic ability may occur between different bacterial species, conjugal mating experiments were performed using strains isolated from children. Donors and recipients were incubated together. ST production by the recipients was tested by the suckling mouse assay, which is the standard biologic method for detecting ST, and also by an ELISA test. The latter is based on MAb directed to Escherichia coli 18- or 19-amino acid toxin. Citrobacter and E. coli strains producing an ELISA-positive ST were used as plasmid donors. Recipients were E. coli, Klebsiella P89, and Klebsiella AL55. The latter had been previously shown to be capable of producing an ELISA-negative ST, but had spontaneously lost this ability. After conjugation, all strains gave positive results in the suckling mouse assay. However, E. coli and Klebsiella P89 ST were positive in the ELISA test, whereas Klebsiella AL55 ST was negative. The same three strains were transformed by inserting the plasmid pSLM004 encoding an ELISA-positive ST. Klebsiella P89 and E. coli became capable of producing an ELISA-positive ST, whereas Klebsiella AL55 cells were positive in the suckling mouse assay but negative in the ELISA. To assess whether the toxigenicity acquired was itself transmissible, the new ST-producing strains were incubated with a nontoxigenic Citrobacter strain. The latter became capable of producing an ELISA-positive ST in all cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Toxins↗

[In vitro examination on antibacterial activities of broad-spectrum antibiotics against gram-negative clinical isolates (author's transl)].

In vitro studies were undertaken on clinically isolated strains of various bacteria to examine the antibacterial activity of ampicillin (AB-PC), carbenicillin (CB-PC), sulbenicillin (SB-PC) cephalothin (CET), cefazolin (CEZ) and gentamicin (GM). Fifty three % of Escherichia coli strains 53.3% of Citrobacter sp., 80% of Proteus mirabilis, 42.9% of Morganella and 80% of Bacteroides sp. were susceptible (MIC being not higher than 12.5 mug/ml) to AB-PC. The eight other species were not so susceptible to this penicillin. CB-PC and SB-PC were almost as effective as AB-PC against Escherichia coli and Citrobacter sp. They were less active against Klebsiella sp., but more active against Enterobacter sp., Serratia sp., indole-positive Proteus group and Pseudomonas sp. than AB-PC, SB-PC was more effective than CB-PC against Pseudomonas sp. The strains of Pseudomonas sp. which were resistant to higher concentrations of CB-PC and SB-PC were pyocyanine-negative strains. All strains (100%) of Escherichia coli, Klebsiella sp. and Citrobacter sp. were susceptible to CET and CEZ, while none of Enterobacter sp. , Serratia sp., Proteus vulgaris. Morganella, Rettgerella, Providencia and Pseudomonas sp. were susceptible to these cephalosporins. The MICs of CET and CEZ against Bacteroides sp. were moderately low. Some strains of Providencia and Alkaligenes sp. were resistant of GM but the other 10 species were not resistant to this antibiotic, though it showed comparatively high MICs against Bacteroides sp. When seen from the MIC distribution of each antibiotic, there was a tendency that the strains isolated from the pus were more resistant than those isolated from the other sources (urine, sputum and bile).

Ampicillin↗

[Aromatic amino acid metabolism in Enterobacteriaceae microorganisms].

The authors revealed phenylalanine deaminase (PAD) in the majority of the Citrobacter strains investigated; the activity of PAD varied within a rather considerable range (0.3--4.58 micrometer of phenylpiruvate in 1 hr per 1 mg of bacterial protein). The presence of this enzyme thus served as an auxiliary biochemical test characterising this group of conditionally pathogenic microbes of the Enterobacteriacea family. Tyrosine decarboxylase was absent in 26 of 50 strains of Citrobacter examined. In the rest of the strains the activity of this enzyme was low. Consequently, tyrosine decarboxylase could not be used for identification of microorganisms of the Citrobacter genus.

Amino Acid Oxidoreductases↗

The detection of nasal carriers of salmonella and other enterobacteria amongst young farm animals.

An investigation was conducted to detect the presence of Salmonella nasal carriers amongst young farm animals (Cow-calves, buffalo-calves, lambs, kids, piglets and foals) on farms having a previous history of Salmonellosis. Salmonella could be isolated from nasal swabs of 1.2% of the cow-calves and 2.9% of the piglets studied but not from other young animals. Isolated strains included S. typhimurium and S. weltevreden from cow-calves and piglets, respectively. Other members of family Enterobacriacteeae isolated from nasal passages of these animals were: E. coli (O106:H27 and O153:H12), Serratia rubidiae, Klebsiella spp., Enterobacter spp. and Citrobacter spp. One of the Citrobacter strains from piglet faeces which appear to be a new Citrobacter serotype had Salmonella 45(1), 45(3), 45(5) 'O' antigens. The results indicated that the upper respiratory tract of animals carried Salmonella and other potentially pathogenic enterobacteria which might contribute to the spread of corresponding infections among man and animals.

Animals↗

Cefamandole resistance transfer in bacterial strains from two newborn units.

Transfer of Cefamandole resistance was demonstrated from strains of Citrobacter freundii as well as from individual strains of Enterobacter cloacae, Acinetobacter anitratus and Klebsiella pneumoniae isolated from patients in two newborn units. In Citrobacter freundii, Cefamandole resistance was transferred always with Cephalotin resistance as well as with a TEM-like beta lactamase (conferring resistance to Ampicillin, Carbenicillin and Azlocillin). Citrobacter freundii strains from Hospital I were completely susceptible to gentamicin, while strains of other species, resistant to Cefamandole plus Cephalotin, were resistant to Gentamicin as well, and transferred this resistance, too. In one Enterobacter cloacae strain from Hospital I, Cefamandole resistance could be separated from resistance to Cephalotin, but only in clones selected with gentamicin and not with any of the cephalosporins. Acinetobacter anitratus strain was also resistant to Cefotaxime, but did not transfer this resistance. It might be concluded that special nosocomial bacteria may carry plasmids conferring a transferable type of resistance to Cefamandole together with resistance to classical cephalosporines. Second cycle of transfers, i.e. between two variants of E. coli K-12 strains confirmed the contransferability of Cefamandole and Cephalotin resistance.

Acinetobacter↗

In vitro activity of cefquinome, a new cephalosporin, compared with other cephalosporin antibiotics.

The in vitro activity of cefquinome, a new aminothiazolyl cephalosporin with a C-3 bicyclic pyridinium group, was compared with ceftazidime, cefpirome, and cefepime. Cefquinome inhibited members of the Enterobacteriaceae at less than or equal to 0.5 microgram/ml for Escherichia coli, Klebsiella pneumoniae, K. oxytoca, Citrobacter diversus, Salmonella Shigella, Proteus mirabilis, Morganella, and Providencia. Although most Citrobacter freundii and Enterobacter cloacae were inhibited by less than 2 micrograms/ml, some strains resistant to ceftazidime were resistant, [minimum inhibitory concentration (MIC) greater than 16 micrograms/ml]. Serratia marcescens were inhibited by less than 1 microgram/ml and Pseudomonas aeruginosa by 8 micrograms/ml similar to the activity of cefepime. The majority of Haemophilus influenzae and Neisseria gonorrhoeae were inhibited by less than 0.25 microgram/ml. Most enterococci had cefquinome MICs of 4-8 micrograms/ml. Cefquinome was extremely active against group-A streptococci and Streptococcus pneumoniae with MICs less than 0.12 microgram/ml. 90% of methicillin-susceptible Staphylococcus aureus 90% were inhibited by 2 micrograms/ml. Overall, the in vitro activity of cefquinome was comparable with aminothiazolyl cephalosporins. It inhibited some Enterobacter and Citrobacter freundii resistant to ceftazidime as did cefpirome and cefepime. Cefquinome was not destroyed by the common plasmid beta-lactamases TEM-1, TEM-2, SHV-1, or by the chromosomal beta-lactamases of Klebsiella, Branhamella, and Pseudomonas, but it was hydrolyzed by TEM-3, TEM-5, and TEM-9. Its activity was not adversely decreased in different medium or protein, and minimum bactericidal concentrations (MBCs) for most species except for Enterobacter were within a dilution of MICs.

Bacteria↗