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[The effect of cefepime on ceftazidime, cefotaxime and imipenem resistant strains of Acinetobacter, Xanthomonas, Pseudomonas, Flavobacterium, Sphingobacterium and on producers of extended spectrum beta-lactamases (ESBL) with resistance transfer].

BACKGROUND: The new cephalosporins with heterocyclic positively charged substituent at position C3 belong to the 4th generation cephalosporins. It is not evident, whereas these antibiotics are effective against cefotaxime-ceftazidime-resistant bacteria. We investigated the efficiency of the cefepime (Maxipime, BMS) against Acinetobacter sp., X. maltophilia, Pseudomonas sp., Flavobacterium sp., Sphingobacterium sp. and against strains with production of ESBL (Extended Spectrum beta-Lactamases) (Enterobacter sp., Citrobacter sp., Klebsiella sp.). METHODS AND RESULTS: We determined the susceptibility of the 54 strains resistant to 50 mg/l and more of ceftazidime. The majority of the strains (35) are susceptible to cefepime and MIC is the range 1.65-3.15 mg/l of cefepime. 17 strains have MIC = 6.25 mg/l. Two strains (one strain P. aeruginosa a one strain K. pneumoniae) were resistant to cefepime and MIC = 12.5 mg/l. The activity of beta-lactamases was determined by quantitative macroiodometric method in one strain of P. cepacia and two strains of Sphingobacterium multivorum. They hydrolyse actively imipenem (they produce metallo-beta-lactamase) and ceftazidime (they are highly resistant to this antibiotic), but cefepime is more slowly hydrolysed than ceftazidime. CONCLUSIONS: At the present time cefepime is effective against ceftazidime-resistant strains in so-called "problematic" species of bacteria. However, it is important to protect its efficiency in the future, this requires its rational use.

Acinetobacter↗

Molecular characterization of a multiply resistant Klebsiella pneumoniae encoding ESBLs and a plasmid-mediated AmpC.

Organisms encoding multiple antibiotic resistance genes are becoming increasingly prevalent. In this report we describe a multiply resistant Klebsiella pneumoniae which possesses at least five different beta-lactamase genes. Isoelectric focusing, polymerase chain reaction and restriction fragment length polymorphism analysis identified TEM-1, multiple SHVs, OXA-9 and a plasmid-mediated ampC, beta-lactamase. Furthermore, Southern analysis and conjugation experiments established that most of the resistance genes were encoded on one large transferable plasmid. This report demonstrates the complexity of multiply resistant organisms.

Adult↗

Effect of D240G substitution in a novel ESBL CTX-M-27.

Escherichia coli clinical strain Gre-1 collected in 2000 from a French hospital harboured a novel CTX-M-encoding gene, designated blaCTX-M-27. CTX-M-27 differed from CTX-M-14 only by the substitution D240G and was the third CTX-M enzyme harbouring this mutation after CTX-M-15 and CTX-M-16. The Gly-240-harbouring enzyme CTX-M-27 conferred to E. coli higher MICs of ceftazidime (MIC, 8 versus 1 mg/L) than did the Asp-240-harbouring CTX-M-14 enzyme. Comparison of CTX-M-14 and CTX-M-27 showed that residue Gly-240 decreased Km for ceftazidime (205 versus 940 microM), but decreased hydrolytic activity against good substrates, such as cefotaxime (kcat, 113 versus 415 s-1), probably owing to the alteration of beta3 strand positioning during the catalytic process.

Amino Acid Substitution↗

[Extended-spectrum beta-lactamase (ESBL) produced by Escherichia coli and Klebsiella pneumoniae isolated from Teikyou University Hospital--the first report].

We studied the cefotaxime (CTX)-resistant (MIC > or = 32 micrograms/ml) clinical isolates of E. coli and K. pneumoniae in Teikyo University Hospital from 1990 to 1996. The incidence of CTX-resistant isolates was 0.4% (6/1,282) in E. coli and 0.6% (7/1,044) in K. pneumoniae, in 1990. In 1995, the incidence of CTX-resistance increased to 1.7% (50/2,910) in E. coli (p = 0.0013) and 7.2% (144/1,996) in K. pneumoniae (p < 0.0001). These species have been detected in the stool (86 isolates), urine (59 isolates), sputum (15 isolates), pus (15 isolates), throat (10 isolates) and others (12 isolates) in 1995. MIC50 of ampicillin (ABPC), ABPC with clavlanic acid (CVA) 5 micrograms/ml, piperacillin (PIPC), PIPC with CVA 5 micrograms/ml, ceftazidime, CTX, ceftizoxime, cefpodoxime, cefepime, aztreonam, cefmetazole, latamoxef, and imipenem used against 33 isolates (11 isolates of E. coli, 22 isolates of K. pneumoniae), which were detected in 1996-1997, was > 512 micrograms/ml, 8 micrograms/ml, > 512 micrograms/ml, 8 micrograms/ml, 4 micrograms/ml, > 512 micrograms/ml, 16 micrograms/ml, > 512 micrograms/ml, 256 micrograms/ml, 32 micrograms/ml, 2 micrograms/ml, 0.25 microgram/ml and 0.25 microgram/ml, respectively. This susceptibility pattern were very similar to the Toho-1 type beta-lactamases producing strains.

Cefotaxime↗

Susceptibility to new beta-lactams of enterobacterial extended-spectrum beta-lactamase (ESBL) producers and penicillin-resistant Streptococcus pneumoniae in Mexico.

The activities of several beta-lactam antimicrobial agents, aminoglycosides and ciprofloxacin, were determined against 62 clinical isolates of enterobacteria resistant to oxyimino cephalosporins (extended-spectrum beta-lactamase producers), collected during 1991 to 1993, and 16 penicillin-resistant invasive isolates of Streptococcus pneumoniae collected during 1994-1996. The numbers and percentages of susceptible enterobacterial strains to tested antibiotics were: imipenem 60 (97%), ciprofloxacin 57 (92%), cefepime 56 (90%), cefpirome 34 (55%), aztreonam 13 (21%), cefotaxime 7 (11%), ceftazidime 0 (0%), amikacin 11 (18%) and gentamicin 16 (26%). Despite the fact that these strains had never been exposed previously to cefepime or cefpirome, the susceptibility was 90% and 55%, respectively. No penicillin-resistant strains of S. pneumoniae were susceptible to cefotaxime, imipenem or cefepime. Only one strain was susceptible to ceftazidime and 4 (25%) were susceptible to cefpirome. Erythromycin showed the greatest activity with 12 (75%) susceptible strains.

Aminoglycosides↗