cefmenoxime and Cross-Infection

Nephrotoxicity frequently complicates the use of aminoglycosides in severely compromised acute care patients. Therefore, an open clinical trial was initiated to determine if cefmenoxime alone is useful in serious nosocomial pneumonias. Thirty consecutive patients were entered in the trial, and 28 patients with an average age of 66 years were evaluable. Most were malnourished at entry, with serum albumin averaging 2.8 g/dl and prognostic nutritional index values over 70 percent (normal less than 40 percent). One-half the patients had severe chronic obstructive pulmonary disease and 68 percent required ventilators. Fifty-seven percent had concomitant cardiac disease, and 79 percent had previously been treated with antibiotics. Pneumonia was proven to be present by new infiltrate on chest x-ray, new fever, elevated white blood cell count, and gram-negative rods on gram stain and in cultures of tracheal aspirates or sputum. Patients were given cefmenoxime 1 to 2 g every six hours an average of 12 days. Cefmenoxime peak (one hour) and trough concentrations were measured by high pressure liquid chromatography and averaged 58 and 7 micrograms ml, respectively. Pharmacokinetic data in 18 patients were determined from serum profiles. Gram-positive organisms, Escherichia coli, Klebsiella, and Hemophilus influenzae were usually eradicated. Persistence was noted for some Enterobacter, Pseudomonas, Serratia, and Acinetobacter. Persistence in patients with good clinical response was considered colonization rather than superinfection. Overall, a satisfactory clinical response rate was noted in 78.6 percent of evaluable patients, whereas four patients responded satisfactorily with recurrence and two treatments had an unsatisfactory response. No serious adverse effects were observed. Cefmenoxime is a promising agent in the treatment of susceptible pneumonias in critical care patients.

Topics: Aged; Bacteria; Blood Proteins; Cefmenoxime; Cefotaxime; Chromatography, High Pressure Liquid; Clinical Trials as Topic; Critical Care; Cross Infection; Female; Humans; Kinetics; Lung; Male; Middle Aged; Pneumonia; Protein Binding; Radiography; Recurrence

To determine if dual individualization of cefmenoxime dosing is cost-effective.. Retrospective, pharmacoeconomic decision analysis of two consecutively conducted prospective clinical studies.. Patients with documented gram-negative nosocomial pneumonia were evaluated. Thirty-three patients received cefmenoxime at standard dosing and 28 patients received doses according to dual individualization methodology.. Antibiotic and infection-related costs were compared between groups. The number of hospital antibiotic days and costs incurred on those days were also evaluated. A decision model was constructed to characterize differences in treatment outcome. Probabilities within the decision tree were derived from 61 evaluable patients. Cost-effectiveness and incremental cost-effectiveness ratios were calculated. Sensitivity analysis was performed by varying outcome probabilities, antibiotic prices, and hospital room costs.. Antibiotic and infection-related costs (mean +/- SEM) were $848 +/- 78 for standard cefmenoxime dosing and $1123 +/- 128 for dual individualization (p < 0.05). Total hospital costs were $10,660 +/- 1432 for standard dosing and $11,709 +/- 1900 for dual individualization (p > 0.05). Median antibiotic length of stay (ALOS) was 15.2 and 12.7 days for standard and dual individualization methodologies, respectively (p > 0.05). Incremental analysis of cost-effectiveness indicated that a similar reduction in length of stay for 259 dual individualization patients would save $321,808 annually.. Sensitivity analysis indicates that, by reducing ALOS, dual individualization could be a cost-effective method of beta-lactam dosing for patients with pneumonia. A prospective study should be conducted to validate these findings.

Topics: Cefmenoxime; Cost-Benefit Analysis; Cross Infection; Decision Trees; Drug Administration Schedule; Drug Costs; Gram-Negative Bacterial Infections; Hospital Costs; Humans; Length of Stay; Pilot Projects; Pneumonia; Time Factors; United States

In vitro, antibiotics are known to kill bacteria in predictable relationships to their broth concentrations. It was our hypothesis that serum concentration was an important determinant of the rate of bacterial eradication in patients. This contention was reinforced by animal studies, which have clearly demonstrated concentration-related antibacterial activity. The animal models rely on reduction of bacterial colony counts as an endpoint of effect, and demonstrate that colony count reductions are related to antibiotic dose and probably to serum concentration. We adapted these methods for use in intubated patients with Gram-negative pneumonia. Briefly, each patient had extensive staging of the pneumonic process, and the Gram-negative organism was isolated and its minimal inhibitory concentration (MIC) was determined. In each patient measurement of the antibiotic serum concentrations in the interval between two doses of the drug was also performed. The pharmacokinetic profile of the drug was then superimposed on the bacterial MIC, and we then derived the patients individual peak to MIC ratio, area above MIC, and time above MIC. Each of these pharmacokinetic parameters was then related to the time required to eradicate the bacterial pathogens in the patient. For beta-lactams and quinolones, time above MIC was the most predictive of bacterial eradication times. Clearly, these methods can be used to develop dosing strategies for patients, as well as to determine clinically relevant doses and dosing strategies in clinical trials. Further work is needed, however, to assess whether these concepts hold for other types of bacteria (such as Gram-positive) or apply as accurately to other infection sites in addition to pneumonia.

Topics: Aged; Aged, 80 and over; Bacterial Infections; Cefmenoxime; Ciprofloxacin; Cross Infection; Female; Gram-Negative Bacteria; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Pneumonia; Prospective Studies; Reproducibility of Results

One hundred sequential Gram-negative rod isolates from patients with hospital-acquired bloodstream infections were tested against seven new cephalosporins. Duplicate broth microdilution tests indicated superior activity for ceftazidime with 97% of strains susceptible to 16 mg/l. Less in-vitro activity was demonstrated cefotaxime (91% susceptible to 16 mg/l, P = 0.07), latamoxef (moxalactam) (90%, P = 0.04), cefoperazone (90%, P = 0.04), ceftriaxone (87%, P = 0.008), cefmenoxime (80%, P = 0.0001), and ceftizoxime (79%, P less than 0.0001). With the exception of cefoperazone, the newer drugs had mean MICs of less than or equal to 0.6 mg/l against Enterobacteriaceae. Ceftazidime and cefoperazone had highest activities against Pseudomonas aeruginosa with MIC90S of 4 and 16 mg/l, respectively. A comparison of recently published data shows important geographic differences in MIC90 data for the new cephalosporins against specific species.

Topics: Cefmenoxime; Cefoperazone; Cefotaxime; Ceftazidime; Ceftizoxime; Ceftriaxone; Cephalosporins; Cross Infection; Enterobacteriaceae; Enterobacteriaceae Infections; Gram-Negative Bacteria; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis

Nephrotoxicity frequently complicates the use of aminoglycosides in severely compromised acute care patients. Therefore, we initiated an open clinical trial to determine if cefmenoxime alone is useful for serious Gram-negative pneumonias in this population. Thirty consecutive patients were studied. Average age was 66 years. Most were malnourished at entry, with serum albumin averaging 2.8 g/dl and prognostic nutritional index values over 70% (normal less than 40%). One-half of the patients had severe COPD and 67.9% were on ventilators. Fifty-seven per cent suffered concomitant cardiac disease, and 78.6% had been previously treated with antibiotics. Pneumonia was proven by new infiltrates on chest X-ray, new fever, elevated WBC count and Gram-negative rods on Gram's stain and in cultures of tracheal aspirate or sputum. Patients were given cefmenoxime 1-2 g every 6 h for an average of 12 days. Cefmenoxime peak (1 h) and trough concentrations were measured by HPLC and averaged 58 and 7 mg/l respectively. Gram-positive organisms, Escherichia coli, Klebsiella spp. and Haemophilus influenzae were usually eradicated. Persistence was noted for Enterobacter, Pseudomonas and Acinetobacter spp. Persistence in patients with good clinical response was considered colonization rather than superinfection. Overall, satisfactory clinical response rate was noted in 78.6%, while four patients responded satisfactorily with recurrence, and two treatments were unsatisfactory. No serious adverse effects were observed. Cefmenoxime is a promising agent for treatment of susceptible pneumonias in critical care patients.

Topics: Aged; Cefmenoxime; Cefotaxime; Critical Care; Cross Infection; Female; Humans; Male; Middle Aged; Pneumonia; Radiography

Cefmenoxime concentration/effect relationships were retrospectively explored for gram-negative bacteria isolated from 14 critical care patients treated for nosocomial pneumonia. The effects of cefmenoxime concentrations on in vitro growth kinetics of 21 isolated pathogens were studied using the Abbott MS-2 Research System, from which a dynamic response concentration was derived. Serum pharmacokinetic profiles were obtained in each patient. These data were used to calculate the in vivo total area under the curve over dynamic response concentration and the time that cefmenoxime concentrations exceeded the dynamic response concentration for each bacteria. The same determinations were made in 18 patients prospectively treated, except that dosage was optimized on the basis of previous mathematical relations to achieve bacterial eradication in four days. This method of dosage optimization is termed dual individualization. Serial cultures of infected tissues were evaluated to determine the number of days to the eradication of bacteria, and the pharmacokinetic and pharmacodynamic variables were used to describe the bacteriologic response of the original pathogen isolated in pretreatment culture. Bacterial eradication rates could be described from cefmenoxime pharmacokinetics in the patient and from the relation between concentration and bacterial inhibition. Patients who were prospectively treated using these retrospectively derived relationships had a predictable day of bacterial eradication. This, in turn, was associated with a shorter duration of treatment (p less than 0.05). The success of prospective dual individualization is encouraging and suggests that more precise optimization of antibiotic dosage can yield a predictable rate of bacterial eradication from the infection site.

Topics: Aged; Cefmenoxime; Cefotaxime; Computers; Cross Infection; Female; Gram-Negative Bacteria; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Pneumonia; Prospective Studies; Retrospective Studies

617 clinical isolates were tested, 592 of which were from hospital source. The minimal inhibitory concentrations of cefmenoxime were determined by a microtiter dilution method, using Mueller-Hinton broth. The results obtained give a 92% agreement with the reference agar-dilution method. Cefmenoxime shows a potent activity against Enterobacteriaceae (n = 420): the modal MIC is less than or equal to 0,03 mg/l, and 90% of them are inhibited by 1 mg/l. Some isolates require a higher concentration, above 32 mg/l: Enterobacter (8%), indole-positive Proteus (13%), Serratia (3%), Citrobacter (3%). Pseudomonas (n = 71) and Acinetobacter (n = 62) appear to be less susceptible than Enterobacteriaceae. The modal MIC is 16 mg/l and the concentration inhibiting 90% of the isolates is above 32 mg/l. The modal MIC of cefmenoxime against Staphylococcus aureus (n = 64) is 1 mg/l, and 90% of the strains belonging to this species are inhibited by 32 mg/l.

Topics: Acinetobacter; Bacteria; Cefmenoxime; Cefotaxime; Cross Infection; Enterobacteriaceae; Humans; Microbial Sensitivity Tests; Pseudomonas; Staphylococcus aureus

The in vitro activity of a new cephalosporin, cefmenoxime, was tested by an agar dilution procedure against 616 strains of Gram negative rods resistant to various beta-lactams and was compared with that of cefotaxime, lamoxactam, ceftazidime (and cefsulodin against P. aeruginosa). A high activity was demonstrated on many species of tested Enterobacteriaceae including E. coli, K. pneumoniae, S. marcescens, E. cloacae resistant to the first generation cephalosporins, Proteus sp., Providencia and C. freundii, with MIC geometric mean values from 0,028 to 0,33 microgram by ml. These values were nearly similar to those given by cefotaxime or lamoxactam and inferior to those given by ceftazidime. Cefmenoxime however showed a low activity (MIC geometric means from 19,5 to 25,5 micrograms by ml) against E. cloacae resistant to second generation cephalosporins (the better agent was lamoxactam), A. calcoaceticus (the better agent was ceftazidime) and carbenicillin-resistant P. aeruginosa (here ceftazidime and cefsulodin gave better performances).

Topics: Anti-Bacterial Agents; Bacteria; Cefmenoxime; Cefotaxime; Ceftazidime; Cephalosporins; Cross Infection; Drug Resistance, Microbial; Enterobacteriaceae; Humans; Moxalactam