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It is generally accepted that the treatment of community-acquired pneumonia, either in adults or in pediatric patients, is mainly empirical. Thus, the treatment selection must fulfill both the epidemiological requirements, according to the most frequently described pathogens, and the pharmacological criteria to ensure adequate and prolonged drug concentrations at the infection site, to reach clinical efficacy. Cefotaxime has proven to be effective in this indication when traditionally administered three times daily and, more recently, twice daily, as a result of a re-evaluation of its pharmacokinetic/pharmacodynamic features. To gain further evidence using this updated dosing schedule, 258 pediatric patients with lower respiratory tract infections were treated with cefotaxime 100 mg/kg/day, administered as a twice daily or three times daily regimen. In the cefotaxime 50 mg/kg twice-daily group (n = 130), a complete resolution of clinical signs and symptoms were observed in 88.5% of patients. Similarly, in the cefotaxime 33.3 mg/kg group (n = 128), 93.6% of patients had a complete resolution of clinical signs and symptoms. Both drug schedules were well tolerated. Pharmacokinetic parameters determined for the two cefotaxime dosing schedules showed comparability. The serum half-life of desacetylcefotaxime was marginally longer than for cefotaxime in both dosage groups (1.64 and 1.36 h for desacetylcefotaxime versus 1.2 and 0.85 h for cefotaxime after 50 mg/kg or 33.3 mg/kg doses, respectively). Results from this study support the use of twice-daily cefotaxime administration for the treatment of lower respiratory tract infections in pediatric patients.

We treated 256 children who had identified bacterial meningitis with cefotaxime. Causative organisms were: Neisseria meningitidis in 108 cases, Streptococcus pneumoniae in 61, Haemophilus influenzae in 60, enteric Gram-negative bacilli in 21, and Staphylococcus spp. in six. Daily doses of cefotaxime were 150-200 mg/kg. A total of 240 patients (93.7%) were cured. In the cured patients, sterilization of cerebrospinal fluid was obtained in the first 72 h of treatment in 214 (80.0%). Cefotaxime is an effective and safe drug for the treatment of childhood bacterial meningitis.

A literature review was carried out to assess the effect of hemodialysis, hemofiltration, and continuous ambulatory peritoneal dialysis on the pharmacokinetics of cefotaxime, particularly in patients with severe renal impairment. It was concluded that the dosage of cefotaxime, adjusted for renal function, would require no further adjustment during peritoneal dialysis or hemofiltration.

A retrospective, matched cohort study was performed to determine the cost outcomes among 495 hospitalized patients who received twice-daily dosing of cefotaxime and 3949 matched cohorts who received other antibiotics. By an attribution model, twice-daily use was associated with shorter mean lengths of stay (-0.498 day, P < .7) and lower mean total costs of hospitalization (-$623, P < .8). Twice-daily dosing of cefotaxime is commonly employed for the treatment of a variety of serious infections, and appears to be cost effective.

Cefotaxime, the first widely used "third-generation" cephalosporin, has established efficacy against a variety of serious bacterial pathogens. Some of the initial clinical studies in the United States using this agent employed large doses of the compound, up to 12 g/day, for adults. In contrast, however, initial European studies were largely with low doses of 1 to 2 g every 12 h. In the recent past, however, an effort has been made, both in the United States and in Europe to reevaluate the dosage of cefotaxime. In various clinical studies, lower doses of cefotaxime have been successfully employed for infections of the urinary tract, peritoneum, biliary tract, lung, and skin and soft tissues. The results of a number of these studies will be reviewed, including a large postmarketing surveillance study carried out in Germany during 1992. The results suggest that cefotaxime doses as low as 1 g, at intervals as long as every 12 h, can be adequate for treatment of the most commonly encountered infections, such as those caused by some hemolytic streptococci, Staphylococcus aureus, Haemophilus spp., and enteric bacilli in nonimmunocompromised patients.

Pharmacodynamic principles have provided important tools to evaluate and compare antimicrobial agents, and well as to guide dosing. For beta-lactams, time above the minimum inhibitory concentration (MIC) has surfaced as the most important factor. However, the area under the inhibitory serum concentration time-curve (AUIC) may be superior when appropriate dosing intervals are selected. Although the target time over the MIC is unclear in humans even when concentrations remain continuously above the MIC, a higher AUIC predicts better clinical outcome up to a maximum. This article provides a pharmacodynamic assessment of 1- and 2-g doses of cefotaxime every 12 h. AUIC24 values and published MIC values for common pathogens (grouped into four groups based on MIC90) were used to predict organisms suitable for treatment with every-12-h regimes. Cefotaxime was inadequate for group 4 organisms including: Pseudomonas aeruginosa, Acienetobacter sp., and Enterococcus sp. Organisms such as Enterobacter cloacae, Serratia marcescens, Staphylococcus aureus, and B. fragilis may be suboptimally treated with cefotaxime every 12 h. Cefotaxime in doses of 1-2 g every 12 h should be useful in patients with normal renal function infected with organisms having MICs < 0.5 microgram/ml. This regimen should obtain AUIC24 values > 125 and ensure adequate time above the MIC. In patients with impaired renal function, because of a longer half-life and higher area under the curve, pathogens with MIC values in the 0.5-2 micrograms/ml range may be treated with cefotaxime every 12 h while maintaining AUICs > 125. Data are also presented for cefotaxime 2 g every 8 h alone and in combination with ofloxacin.(ABSTRACT TRUNCATED AT 250 WORDS)

Available information on the pharmacokinetics of cefotaxime (CTX) and desacetylcefotaxime (dCTX) indicates that their disposition depends on development, with the greatest changes occurring during the 1st year of life. To a great extent, these changes reside with the acquisition of renal function (e.g., both glomerular filtration and active tubular secretion) during the 1st year of life. When the impact of development on CTX and dCTX disposition is considered, it is apparent that age-appropriate pharmacokinetic data can be used to individualize CTX dosing regimens according to age. Also, alternative dosing regimens that have been proven to be both safe and effective can be justified.

To assess the efficacy of cefotaxime in the treatment of severe intra-abdominal infections, we reviewed the bacteriology of secondary peritonitis and evaluated the efficacy of cefotaxime and metronidazole in 79 patients undergoing staged abdominal repair. We were able to demonstrate that the combination of an aggressive surgical policy with an effective antimicrobial regimen eliminates pathogens from the previously infected peritoneal cavity. Additional improvement in results awaits further advances in supportive care and/or methods to reverse the cascades of the excessive inflammatory or cytokine responses.

A retrospective analysis of the clinical and economic outcome of a regimen of cefotaxime 1 g given every 12 h was conducted following the introduction of an institutional policy recommending this new dosing strategy. Patients were identified from a log order entry in the pharmacy, and the medical records were reviewed using a standardized data collection form. Explicit criteria were applied for the indications for antimicrobial therapy, presence of infection, and outcome parameters. A total of 60 patients with a mean (+/- SD) age of 56.2 (+/- 17.8) years and a mean (+/- SD) length of stay of 20.75 (+/- 18.1) days were identified. Of these, 48 (80%) were found to have a clinically or microbiologically documented infection, and of the 42 patients who could be assessed accordingly to the criteria chosen, 37 (88%) had a favorable clinical response; 21 patients (35%) received cefotaxime alone. The costs for administration of cefotaxime have decreased by approximately 30% since the introduction of this new dosing regimen.

A total of 548 patients with postoperative pneumonia were treated with 1 or 2 g cefotaxime twice daily. Of the 88 patients without serious underlying diseases who received the 1-g 12-h dosage regimen, all were considered to be clinically cured, and all 54 isolated pathogens were eradicated or presumed to be eradicated. In the group with severe infection or severe underlying disease receiving 2 g 12-h cefotaxime, the overall clinical success rate (cured plus improved) was 98.4%. Results from this study support the use of cefotaxime as an alternative to empiric monotherapy for nosocomial pneumonia in surgical-service patients who are not neutropenic or on long-term artificial ventilation.

Neonatal sepsis is a clinical syndrome characterized by systemic signs and symptoms, and bacteremia during the first month of life. The incidence is relatively low (one to eight cases/1000 live births), yet the risk of mortality is approximately 25%. Meningitis in the neonate is usually a sequela of bacteremia; however, it is discussed with neonatal sepsis, because they commonly share etiology and pathogenesis. The incidence of meningitis is usually a fraction of the number of infants with sepsis, varying in different settings from one-fourth to one-third. The mortality rate is high, varying in some series from 15%-50%. There are two major forms of presentation of neonatal sepsis. Early-onset disease presents as a fulminant, multisystemic illness during the first 5-7 days of life; late-onset disease is more commonly recognized after the first weeks of life. Because different microorganisms are responsible for the two forms of disease, the choice of antimicrobial agents also differs. Some organisms such as Escherichia coli, group B streptococci, and Listeria monocytogenes may be responsible, whereas other pathogens such as Staphylococcus aureus and S. epidermidis, and Pseudomonas aeruginosa are usually associated with late-onset disease. Classic initial (empiric) treatment of neonatal sepsis and meningitis consists of ampicillin and an aminoglycoside. With the advent of the third-generation cephalosporins, however, the empiric antimicrobial approach for neonatal sepsis and meningitis has changed in most centers. Third-generation cephalosporins cover more of the pathogens implicated in neonatal sepsis and meningitis, except for the enterococci and L. monocytogenes.(ABSTRACT TRUNCATED AT 250 WORDS)

Spontaneous bacterial peritonitis (SBP) is a severe infectious complication in cirrhotic patients, and initial antibiotic therapy must be empirical. An initial study published in 1985 found that cefotaxime administered at a dose of 2 g every 4 h was more effective and safer than the combination of tobramycin-ampicillin. Since then, cefotaxime has been considered the agent of choice in the empiric therapy of SBP. Subsequent publications showed that a dosage of 2 g every 6 h was also adequate in this infection. More recent studies have demonstrated that the high efficacy of cefotaxime in SBP can be maintained by using lower dosages than those used in initial investigations. In one of these studies, a dose of 2 g every 8 h for 5 days was found to be as effective as the same dose for 10 days. Finally, a prospective, randomized multicenter trial aimed at comparing the efficacy of two different dosages of cefotaxime, 2 g every 6 h versus 2 g every 12 in a large series of cirrhotic patients with SBP, showed that both dosages resulted in similar rates of resolution of infection and survival. Despite the reasonably adequate rate of infection resolution in SBP patients, the in-hospital mortality rate remains high as a result of complications such as renal failure. Further studies should therefore be addressed to reducing the incidence of these complications and thus improving survival.

Cefotaxime has been used extensively in many pediatric centers in the United States for the past 10 or more years. Its main usage has been for the treatment of various serious bacterial infections in pediatric patients, primarily meningitis and sepsis. It has also been used to treat intraabdominal, urinary tract, soft tissue, bone, and joint infections. Although there has been a marked reduction in the incidence of invasive Haemophilus influenzae type b infections following the introduction of effective vaccines, cefotaxime remains very useful against the other common pathogens causing serious infections in pediatric patients. The increasing number of pneumococci resistant to penicillin and third-generation cephalosporins has created a new challenge for the management of serious pneumococcal infections. In many institutions, cephalosporins in general have been overused and abused, resulting in the emergence of resistant organisms and an increasing burden on resources. The judicious use of cefotaxime and other cephalosporins should be emphasized.

Cefotaxime 2 g every 12 h was administered to adults with severe nosocomial pneumonia in a prospective noncomparative study. The results confirmed that this regimen is adequate and appropriate therapy for nosocomial pneumonia, with the combination of cefotaxime and an aminoglycoside reserved for cases where multiresistant, Gram-negative bacterial infections are strongly suspected.

Clinical studies of cefotaxime administered every 8 and 12 h have demonstrated comparable clinical and microbiologic success when compared to traditional 6-h regimens. This phenomena may be explained, in part, by the pharmacokinetic and pharmacodynamic properties of cefotaxime and the antimicrobially active metabolite desacetyl-cefotaxime. Although cefotaxime levels cannot be maintained above the bacterial minimum inhibitory concentration (MIC) for all infecting pathogens with extended dosing intervals, concentrations of desacetyl-cefotaxime remain above the effective concentration for a variety of organisms throughout the extended interval. Cefotaxime dosage adjustment may be accomplished in nonimmunocompromised patients with infections outside the central nervous system including uncomplicated urinary tract and lower respiratory infections. Infections caused by bacteria with MIC90 values < or = 1 microgram/ml usually respond to 8- or 12-h dosage intervals. Less susceptible organisms with MIC90 values between 2 and 8 micrograms/ml, such as Serratia marcescens, may initially require cefotaxime administered every 6 or 8 h. Extended intervals should be avoided or used cautiously in patients that are neutropenic, immunocompromised, or hypermetabolic. Upon evidence of clinical and microbiologic response, therapy may be continued with alternative stepdown therapy.

In a Swedish multicenter, comparative, retrospective study, patients with different types of infections--bacteremia-septicemia, genitourinary, intra-abdominal, central nervous system, and lower respiratory tract infections--were randomly selected from the hospital records. Patients treated with cefotaxime twice or three times a day as monotherapy (excluding metronidazole) for at least 1 day (240 cases) were analyzed in terms of clinical and bacteriologic outcome, these results were correlated with the dosing regimen. Similarly high success rates (cure and improvement) at hospital discharge were observed in both group initially treated with cefotaxime 1 g twice daily and 2 g twice daily (97 and 96%, respectively). A total of 73% of patients were initially treated with cefotaxime for only 3 days at most before changing to a lower dose regimen, an alternate intravenous treatment, or oral drug follow-up. Clinical evaluation at hospital discharge revealed a clinical success rate between 87 and 100%, depending on the type of infection.

Third-generation cephalosporins are the drugs of choice for serious nosocomial pneumonia; however, the recommended dosages are controversial. Our study compared two of these cephalosporins and showed that 2 g cefotaxime every 12 h and 4 g ceftriaxone once daily or 2 g every 12 h proved to be effective therapies for these chest indications.

We randomized 365 patients with serious infections to treatment with either 2 g intravenously (IV) cefotaxime every 12 h or 2 g IV ceftriaxone once daily. Clinical response rates were similar in both treatment groups, with success defined as satisfactory or improved response in 107 of 124 (86.3%) evaluable patients in the cefotaxime group compared with 103 of 114 (90.4%) evaluable patients in the ceftriaxone group. Bacteriologic cure rates were also similar in the two groups (86.4%) in the cefotaxime group compared with 87.0% in the ceftriaxone group). There was no statistically significant difference in the incidence of drug-related adverse events in the two groups. These results indicate that 2 g cefotaxime twice daily is as effective, both clinically and bacteriologically, as 2 g ceftriaxone once daily in serious infections caused by susceptible pathogens.

Cefotaxime 1 g intramuscularly (i.m.) 12-hourly was compared with ceftriaxone 1 g i.m. 12-hourly in adult patients requiring hospitalization with uncomplicated community-acquired pneumonia. Fifty-two patients were enrolled and two were subsequently withdrawn, leaving 50 patients who completed the study; 23 received cefotaxime and 27 received ceftriaxone. Clinical cure was achieved in 49 of the 50 patients (98%). One treatment failure occurred in a patient who received ceftriaxone. The only significant pathogen isolated from the pretreatment sputum cultures was Streptococcus pneumoniae (50%). All isolates were sensitive to both drugs. Cefotaxime 1 g i.m. 12-hourly was as effective as ceftriaxone in the treatment of patients with uncomplicated community-acquired pneumonia requiring hospital admission.

A multicenter Canadian study enrolled 74 persons to compare low-dose cefotaxime at 1 g every 8 hr to ceftriaxone 1 g every 12 hr in patients with nosocomial pneumonia. Of 57 evaluable patients (30 cefotaxime and 27 ceftriaxone) in this preliminary report, 93% responded to therapy in both groups. Ceftriaxone patients tended to have more side effects (14.2%). This study is continuing to accrue patients to achieve 100 evaluable patients. Interim data, however, support the continued use of low-dose cefotaxime as an appropriate alternative for clinically effective and cost-effective management of nosocomially acquired pneumonia.

Thirteen adult patients (47-81 yr) with gram-negative bacteremia and normal (less than or equal to 1.5 mg/dl) serum creatinines were treated with 1 or 2 gm of cefotaxime every 8 or 12 hr. The infecting organisms were Escherichia coli (9 strains), Klebsiella pneumoniae (2 strains), and one isolate of Salmonella enteritidis and Serratia marcescens. All patients recovered without any serious sequelae. The range of MICs for cefotaxime and desacetyl-cefotaxime were 0.015-0.25 micrograms/ml and 0.015-4.0 micrograms/ml, respectively. The MBC values for cefotaxime and desacetyl-cefotaxime were identical to the MIC values except for two strains. The trough levels of cefotaxime varied from 65.9 to 1.1 micrograms/ml. The serum concentration of desacetyl-cefotaxime varied from 84 to less than 1.0 microgram/ml. All corresponding trough serum inhibitory activities (SIA) were greater than or equal to 1:32. Comparisons of calculated and directly measured serum bactericidal activity (SBA) and SIA results suggest an additive and occasional synergistic benefit of the cefotaxime desacetyl metabolite. This study supports the clinical efficacy and cost-effectiveness of 8- and 12-hr dosing intervals for cefotaxime against bacteremic gram-negative strains having the usual high susceptibility (MICs, less than or equal to 0.25 micrograms/ml) to the newer cephalosporins.

Single 3.1-g dose surgical prophylaxis with ticarcillin/clavulanic acid (Timentin) was compared to single-dose cefotaxime. Among 224 evaluable cases, the Timentin associated wound infection rate (0.7%), nonwound infectious morbidity (8.8%), adverse reactions (1.9%), and total costs ($14.15) were not statistically different than that of the control drug. The beta-lactamase [corrected] inhibitor combination reported herein should be considered along with other beta-lactams [corrected] for use as a cost-effective, single-dose surgical prophylaxic agent on a wide variety of operative procedures.

Thirty-one patients with Gram-negative bacteremia with organisms susceptible to cefotaxime (CTX) (MIC of 1 microgram/ml or less) were randomized to receive 2 g of CTX every 6, 8, or 12 hr. Five-hour susceptibility studies were performed on a bacterial pellet obtained from the patient's positive blood culture vial. Thus, patients were enrolled within hours after Gram-negative organisms were demonstrated in their blood cultures. All bacteremias were cleared although two patients had unsatisfactory responses to therapy. Trough serum bactericidal levels were 1:2 or greater in all patients. This study supports that CTX can be used at an 8- or 12-hr intervals in selected patients with Gram-negative bacteremia.

A study of the pharmacokinetic parameters of cefotaxime (CTX) and desacetylcefotaxime (dCTX) in newborns was conducted; the former is commonly used for neonatal infections. The elimination half life of CTX correlated with gestational age (GA) and postnatal age (PNA). Elimination of dCTX was longer permitting a synergistic or additive effect with CTX against Gram-negative bacteria. CTX is indicated in the treatment of neonatal sepsis because of the increasing resistance of Escherichia coli to ampicillin and its good efficacy against group B streptococcus.