Minimum Inhibitory Concentrations Of Cefotaxime Research Articles

Activity of cefotaxime/desacetylcefotaxime with two aminoglycosides against gram-negative pathogens: an example of interactive synergy.

The susceptibility patterns of clinical Gram-negative isolates were determined to cefotaxime (CTX) and desacetylcefotaxime (dCTX) alone and in combination with gentamicin (GENT) or tobramycin (TOB) by an agar dilution technique. A constant ratio of 1:1 (CTX to dCTX) was tested throughout the study. Isolates were challenged with subinhibitory levels of TOB or GENT in combination with clinically achievable levels of CTX, dCTX and CTX/dCTX to examine the interactions of the agents. Results of this study demonstrate that CTX/dCTX interacts synergistically with aminoglycosides against many Gram-negative pathogens. Synergy (defined as a fourfold or greater decrease in minimum inhibitory concentration (MIC) when CTX/dCTX was compared to CTX/dCTX/TOB) was demonstrable for 55% of isolates tested. Similarly, 45% were synergistically inhibited by CTX/dCTX/GENT. Additivism (a 2-fold decrease in MIC with the same comparisons) was evident for an additional 18 isolates for CTX/dCTX/TOB and 19 with CTX/dCTX/GENT. When data for Pseudomonas spp. were excluded from the analysis, synergy or additivism was evident with CTX/dCTX/TOB for 88% of the organisms tested and 72% with CTX/dCTX/GENT. Synergistic synergy for CTX/dCTX/TOB (an 8- to greater than 16-fold decrease in MIC for CTX) was demonstrable for 35 and 32 of 82 nonspeudomonal isolates respectively with the TOB and GENT combinations. Ninety nine percent of the nonspeudomonal isolates were inhibited by less than 4 micrograms/ml of CTX, 4 micrograms/ml of dCTX and 0.12 micrograms/ml of TOB, or 0.25 micrograms/ml of GENT, respectively.

TRANSFERABLE ENZYMATIC RESISTANCE TO THIRD-GENERATION CEPHALOSPORINS DURING NOSOCOMIAL OUTBREAK OF MULTIRESISTANT KLEBSIELLA PNEUMONIAE

Klebsiella pneumoniae strains that were resistant to third-generation cephalosporins and amikacin were recovered from 62 of 395 patients (15.7%) during 1986. 25 isolates (40%) caused urinary tract infections. The outbreak involved three intensive care units (54 isolates), and spread from one unit to another and then to four wards (8 isolates). K pneumoniae of various serotypes and strains of different Enterobacteriaceae demonstrating the same antibiotic resistance pattern were isolated, which suggests dissemination of an R-factor. The isolates had low-level resistance to third-generation cephalosporins (mode minimum inhibitory concentration of cefotaxime, 2 mg/l) but remained sensitive to cephamycins. Cefotaxime was effective in cases of uncomplicated urinary tract infection, but failed in major infections at other sites. 1-5 mg/l of the β-lactamase inhibitors clavulanic acid or sulbactam restored normal activity to cefotaxime against the multiresistant strains. Resistance to third-generation cephalosporins was mediated by a new broad-spectrum enzyme of isoelectric point 6.3. Resistance to β-lactams and aminoglycosides was transferable to Escherichia coli. The emergence of transferable enzymatic resistance to newer β-lactams in K pneumoniae strains indicates a major risk of spread of such resistance to otherwise sensitive strains.

Penicillinase-producing Neisseria gonorrhoeae isolates from different localities in south east Asia. Susceptibility to 15 antibiotics.

Sixty four penicillinase-producing Neisseria gonorrhoeae (PPNG) and 24 non-penicillinase-producing (non-PPNG) strains isolated from six different south east Asian localities were tested by the agar dilution method against 15 antibiotics. All isolates were susceptible to spectinomycin and sulphamethoxazole-trimethoprim (19:1 ratio). A large proportion of both PPNG and non-PPNG strains showed, however, a decreased susceptibility to tetracycline, kanamycin, and erythromycin: 49% with minimum inhibitory concentrations (MICs) of tetracycline greater than or equal to 2 micrograms/ml, 34% with MICs of kanamycin greater than or equal to 32 micrograms/ml, and 80% with MICs of erythromycin greater than or equal to 2 micrograms/ml. These MIC cut-off values were chosen since they are close to the highest concentrations of these antibiotics attainable in serum after drug administration. Resistance to these antibiotics was not related to penicillinase production and does not appear to be confined to gonococci isolated from one particular locality. Strains showing resistance concurrently to two or three of these drugs were often isolated from different south east Asian countries. All eight cephalosporins tested were effective against both PPNG and non-PPNG strains. On a weight to weight basis the new cephalosporins--namely, moxalactam, cefoperazone, cefotaxime, and ceftriaxone--were the most effective. In contrast to those of cefoxitin, cefuroxime, moxalactam, and cefoperazone the MICs of cefamandole, cefotaxime, and ceftriaxone were significantly affected when the inoculum size was increased from 10(3) to 10(6) colony forming units (cfu).

Susceptibility of Neisseria gonorrhoeae to cefotaxime and ceftizoxime.

Two hundred and thirty-nine penicillinase-positive and 240 penicillinase-negative strains of Neisseria gonorrhoeae were tested for their susceptibility to cefotaxime. All were susceptible to cefotaxime at a concentration of 0.062 micrograms/ml. Penicillinase-negative strains were less susceptible than penicillinase-positive strains. This is attributed to the use of prophylactic antibiotics by prostitutes, which has led to the selection of less susceptible penicillinase-negative strains but has not affected the susceptibility of penicillinase-positive strains. The minimum inhibitory concentrations of cefotaxime showed significant positive correlations with those of penicillin, ampicillin, tetracycline, and kanamycin but had a negative correlation with spectinomycin. The related cephalosporin, ceftizoxime, was found to be as effective as cefotaxime against penicillinase-positive and penicillinase-negative gonococci.

INTRAVENOUS CEFOTAXIME IN CHILDREN WITH BACTERIAL MENINGITIS

Thirteen children with meningitis due to Hœmophilus influenzœ, β-hæmolytic streptococcus group B, Streptococcus pneumoniœ, Staphylococcus epidermidis, Neisseria meningitidis, Escherichia coli, or Pseudomonas œruginosa and who had been unsuccessfully treated with other antibiotics or had causative organisms which were resistant to available antibiotics were treated with intravenous cefotaxime. Nine children were cured; in one case infection (with a different organism) recurred but a further course of cefotaxime was successful; one child died, with sterile CSF; one child died from his underlying disease (astrocytoma); and one child was cured with sequels (hydrocephalus). A further child with meningitis caused by E. coli had been treated unsuccessfully by intravenous and intraventricular chloramphenicol and gentamicin; intravenous and intraventricular cefotaxime was successful. The agent was well tolerated. CSF levels were measured in seven children and ranged from 300 to 27 200 μg/l; published and unpublished in-vitro studies suggest that minimum inhibitory concentrations for cefotaxime against the organisms commonly causing bacterial mem- ingitis are usually well below 250 μg/l.