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PubMed1986

[Clinical and laboratory evaluations of ceftazidime in perinatal use. A study of ceftazidime in the perinatal co-research group].

Efficacy and safety of ceftazidime (CAZ) in women during the perinatal period and their neonates were evaluated by a perinatal co-research group, and the results obtained were summarized as follows. Following an intravenous bolus injection or a drip infusion of CAZ from 1 g to 2 g, CAZ was transferred to maternal serum, umbilical cord serum and amniotic fluid rapidly and effectively. In 31 cases of perinatal infections, clinical efficacy was excellent in 10 cases, good in 18 and poor in 3, with an efficacy rate of 90.3%. In 85 cases given CAZ for prophylaxis of infections accompanying premature rupture of the membrane or following cesarean section, prophylactic effects were noted in 81 cases (efficacy rate: 95.3%). Neither adverse effects, nor abnormal laboratory findings were observed in any case. Also, no abnormalities in total serum bilirubin were observed in any neonates. From the above results, CAZ is considered to be a safe and useful drug for infections in women in perinatal period, usually in a unit dose of 1 g twice daily, or if necessary, 2 g twice daily.

Adult↗
PubMed1989

Intravenous ciprofloxacin or ceftazidime in selected infections. A prospective, randomized, controlled study.

In a prospective, randomized, controlled study, the effectiveness and safety of intravenous ciprofloxacin was compared with those of ceftazidime in the treatment of tissue infections. A total of 52 patients received intravenous ciprofloxacin 200 mg twice daily (26 patients) or ceftazidime 1 to 2 g every eight to 12 hours (26 patients). This was followed, respectively, by oral ciprofloxacin or another suitable drug when improvement was seen. Informed consent was obtained from all patients. Cultures and laboratory determinations were performed initially and repeated periodically as indicated. Both groups were comparable in age, sex, number of infected sites, and instance of nosocomial infections (27 total). Severe infections occurred in six ciprofloxacin and 12 ceftazidime patients (p = 0.056). There were 13 patients in the ciprofloxacin group and six in the ceftazidime group with accompanying diseases (p = 0.032). Patients were treated with ciprofloxacin or ceftazidime for infections of the urinary tract (eight and two patients, respectively), skin or soft tissues (15 and 17 patients), pelvis (one and zero patients), lower respiratory tract (one and one patients), intra-abdominal (zero and three patients), and bacteremia (three and five patients). Two patients in each group had two sites of infection. Causative organisms were as follows: 15 gram-positive cocci (90 percent minimal inhibitory concentration: ciprofloxacin, 0.5; ceftazidime, 16.0 micrograms/ml) and 55 gram-negative rods (44 Enterobacteriaceae, nine Pseudomonas aeruginosa; 90 percent minimal inhibitory concentration: ciprofloxacin, 0.25; ceftazidime, 8.0 micrograms/ml). Resistance emerged in one patient treated with ciprofloxacin (Acinetobacter sp.) and 12 treated with ceftazidime (four Enterococcus, two Staphylococcus aureus, six other). Intravenous treatment was longer with ceftazidime (11.5 days versus 5.6 days for the ciprofloxacin group, p less than 0.0005), but the total duration of therapy was similar (12.9 versus 14.1 days, p value not significant). Resolution or improvement occurred in 23 ciprofloxacin and 26 ceftazidime sites of infection (p value not significant). Death occurred in two ceftazidime-treated patients (due to bacterial infection) and one ciprofloxacin-treated patient (at the induction of anesthesia). Adverse experiences were more common in the ceftazidime group as compared with the ciprofloxacin group (22 versus 15 patients, p = 0.026). Ciprofloxacin eradicated 25 of 31 causative organisms, whereas ceftazidime eradicated 30 of 41 (p value not significant). Intravenous ciprofloxacin was at least as effective as ceftazidime. Patients treated with ciprofloxacin may need added coverage for anaerobes, but the drug's excellent activity against nosocomial pathogens and its availability in oral form allow for an early change to oral therapy without compromising effectiveness coupled with added savings and convenience.

Adult↗
PubMed1996

Comparative Effects of Ceftazidime Two or Three Times Daily in Patients with Skin and Skin Structure Infections.

BACKGROUND: Skin and skin structure infections are among the most common infectious diagnoses in both the hospital and community settings. If untreated, these infections can produce serious complications. Successful antimicrobial therapy for these infections requires coverage against the causative pathogens, particularly Staphylococcus aureus. OBJECTIVE: This randomized, single-blind, multicenter study was designed to compare the efficacy and safety of intravenous ceftazidime 2 g given two times daily (BID) with that of intravenous ceftazidime 1 g given three times daily (TID) for the treatment of skin and skin structure infections caused by ceftazidime-sensitive pathogens. METHODS: Adults (greater-than-or-equal18 years) were eligible for enrollment if they were hospitalized or in home health care settings and they had a skin or skin structure infection caused by a ceftazidime-sensitive pathogen. Patients were randomly assigned to receive ceftazidime 2 g every 12 h or ceftazidime 1 g every 8 h as an intermittent infusion over 15--30 min. Treatment was continued for 2--3 days beyond the time the patient became asymptomatic or evidence of bacterial eradication was obtained; however, total treatment duration had to be at least 5 days. Patients were assessed for their clinical and bacteriological response at the end of treatment and for their clinical response at follow-up. RESULTS: A total of 806 patients were enrolled in the study, 406 of whom received ceftazidime 2 g BID and 400 of whom received ceftazidime 1 g TID. Both treatments were administered for a mean duration of 9 days. At the end of therapy, 248 of 264 (94%) clinically evaluable patients receiving ceftazidime BID and 258 of 275% (94%) clinically evaluable patients receiving ceftazidime TID achieved clinical cure or improvement (p = 0.953). Pathogens were eradicated or presumed to be eradicated from 217 of 256 (85%) bacteriologically evaluable patients receiving ceftazidime BID and from 228 of 266 (86%) bacteriologically evaluable patients receiving ceftazidime TID (p = 0.760). Of 1131 isolates, the most common pathogens were S. aureus (30%) and Pseudomonas aeruginosa (10%). Both regimens were well tolerated with only 13 patients (3%) in the BID group and 16 patients (4%) in the TID group withdrawing because of an adverse event. CONCLUSIONS: These data indicate that ceftazidime 2 g given twice daily is as effective as ceftazidime 1 g given three times daily for the treatment of skin and skin structure infections. In addition, the twice-daily regimen has the advantage of convenience.

Journal Article↗
PubMed1985

Aspects of clinical trials with ceftazidime worldwide.

Overall results from worldwide clinical studies of ceftazidime in open and comparative trials conducted over a four-year period in North America, Europe, and elsewhere are presented. Data from 3,570 patients treated with ceftazidime in open studies and from 1,340 patients receiving ceftazidime and 1,180 patients receiving other antibiotics in comparative studies are discussed. The comparative antibiotics consisted of aminoglycosides alone in 14.2 percent of patients, aminoglycosides combined with one or two beta-lactams in 43 percent, beta-lactams alone in 34 percent, and other antibiotic combinations in 8.8 percent. In comparative studies, bacterial clearance rates were 80.6 percent for ceftazidime and 72.5 percent for other antibiotics. Clinically, 92.6 percent of the infected sites in ceftazidime-treated patients in open studies were cured or improved, and 91.1 percent were cured or improved in comparative studies; 84.8 percent of the infected sites were cured or improved in patients treated with other antibiotics. Data indicate that ceftazidime monotherapy is as effective as combination antibiotic therapy in the empiric treatment of febrile non-neutropenic patients. The role of ceftazidime monotherapy in the treatment of febrile neutropenic patients is not yet firmly established. Superinfections were reported in 2.6 percent of the patients treated with ceftazidime alone in open trials, in 4.2 percent of the patients treated with ceftazidime alone in comparative trials, and in 8.5 percent of the patients treated with other antibiotics. During treatment, the sensitivity of bacteria to ceftazidime decreased in 2.5 percent of the pathogens isolated. Adverse events occurred in 10.2 percent of patients treated with ceftazidime in open studies, in 8.4 percent of those treated with ceftazidime in comparative studies, and in 8.8 percent of those treated with other antibiotics. The adverse events in both ceftazidime- and control-treated patients were thought by the investigators to be drug-related in about 40 percent of cases, not drug-related in 20 percent of cases, and of unknown etiology in the remaining cases.

Bacterial Infections↗
PubMed1995

Pharmacodynamics of ceftazidime administered as continuous infusion or intermittent bolus alone and in combination with single daily-dose amikacin against Pseudomonas aeruginosa in an in vitro infection model.

We compared the pharmacodynamics and killing activity of ceftazidime, administered by continuous infusion and intermittent bolus, against Pseudomonas aeruginosa ATCC 27853 and ceftazidime-resistant P. aeruginosa 27853CR with and without a single daily dose of amikacin in an in vitro infection model over a 48-h period. Resistance to ceftazidime was selected for by serial passage of P. aeruginosa onto agar containing increasing concentrations of ceftazidime. Human pharmacokinetics and dosages were simulated as follows: half-life, 2 h; intermittent-bolus ceftazidime, 2 g every 8 h (q8h) and q12h; continuous infusion, 2-g loading dose and maintenance infusions of 5, 10, and 20 micrograms/ml; amikacin, 15 mg/kg q24h. There was no significant difference in time to 99.9% killing between any of the monotherapy regimens or between any combination regimen against ceftazidime-susceptible P. aeruginosa. Continuous infusions of 10 and 20 micrograms/ml killed as effectively as an intermittent bolus of 2 g q12h and q8h, respectively. Continuous infusion of 20 micrograms/ml and an intermittent bolus of 2 g q8h were the only regimens which prevented organism regrowth at 48 h, while a continuous infusion of 5 micrograms/ml resulted in the most regrowth. All of the combination regimens exhibited a synergistic response, with rapid killing of ceftazidime-susceptible P. aeruginosa and no regrowth. Against ceftazidime-resistant P. aeruginosa, none of the ceftazidime monotherapy regimens achieved 99.9% killing. The combination regimens exhibited the same rapid killing of the resistant strain as occurred with the susceptible strain; however, regrowth occurred with all regimens. The combination regimens of continuous infusion of 20 micrograms/ml plus amikacin and intermittent bolus q8h or q12h plus amikacin continued to be synergistic. Overall, continuous infusion monotherapy with ceftazidime at concentrations 4 to 5 and 10 to 15 times the MIC was as effective as an intermittent bolus of 2 g q12h (10 to 15 times the MIC) and q8h (25 to 35 times the MIC), respectively, against ceftazidime-susceptible P. aeruginosa. Combination therapy with amikacin plus ceftazidime, either intermittently q8h or by continuous infusion of 20 micrograms/ml, appeared to be effective and exhibited synergism against ceftazidime-resistant P. aeruginosa.

Amikacin↗
PubMedDate not supplied

In vitro activity of ceftazidime in combination with other antibiotics.

189 bacterial strains were investigated for their in vitro sensitivity against ceftazidime (alone and in combination with another antibiotic). Moreover, the possibility to prevent development of secondary bacterial resistance as observed in subcultures at subinhibitory antibiotic concentrations, was studied using specific antibiotic combinations. Of 115 staphylococcal strains (91 strains of Staphylococcus aureus, 24 strains of Staphylococcus epidermidis), 2% were sensitive, 82% were moderately sensitive and 16% were resistant to ceftazidime. On combining ceftazidime with vancomycin, synergism was found in 61% of the strains, and secondary resistance to ceftazidime could be prevented with this combination. The combination of ceftazidime and clindamycin showed synergism in 26% and an additive effect in 48% of the strains. Secondary resistance to ceftazidime did not develop with this combination in subcultures at subinhibitory concentrations in which loss of activity was only minimal with clindamycin alone. Rifampicin and fusidic acid were highly active against staphylococci. In combination with ceftazidime, only weak synergism or additive effects were seen in most strains; no antagonism could be observed. In subcultures at subinhibitory concentrations, secondary resistance to rifampicin and fusidic acid developed rapidly and could be partially prevented by adding ceftazidime. Of 60 Pseudomonas aeruginosa strains, 84% were sensitive, 13% were moderately sensitive and 2% were resistant to ceftazidime. Synergism was most frequently observed when ceftazidime was combined with tobramycin. Using this combination, secondary resistance of Pseudomonas strains to ceftazidime did not develop. When ceftazidime was combined with piperacillin, synergism was observed in most strains, but the development of secondary resistance in vitro was not prevented.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗
PubMed1998

A kinetic oxymoron: concentration-dependent first-order rate constants for hydrolysis of ceftazidime.

The influence of pH, temperature, and buffers on the hydrolysis of 10(-4) M ceftazidime was previously reported. The pH-rate profiles showed that maximum stability occurred in the pH-independent region from 4.5 to 6.5. In the present study, hydrolysis rates of 0.031, 0.14, 0.25, and 0.35 M ceftazidime were measured at 30 and 65 degrees C, pH 5.5-6.2. The data were consistent with beta-lactam hydrolysis and the rapid release of pyridine. The sum of the time-dependent concentrations of ceftazidime and pyridine provided mass balance. Simultaneous nonlinear regression for ceftazidime loss and pyridine formation provided similar rate constants (k) to those determined from first-order plots of ceftazidime loss. Although the loss of ceftazidime was first-order for each initial concentration, the k values increased as the initial concentrations increased. Plots of k versus initial concentration were linear with intercepts similar to the k values for 10(-4) M solutions, thus implying that ceftazidime catalyzed its own degradation. At the pH of these studies ceftazidime exists as a base. The ceftazidime catalytic constant, calculated from the slope of the plot, was similar to that found for the general-base catalyst, HPO4(2-). Therefore, it is feasible that ceftazidime also behaved as a intermolecular general-base catalyst. However, first-order plots exhibited excellent linearity even though the catalyst (ceftazidime) was consumed. This would require that the catalytic moieties on ceftazidime remained relatively constant throughout its hydrolysis. This hypothesis was shown to be consistent with literature reports which indicate that the general-base catalytic groups can remain relatively constant during cephalosporin hydrolysis.

Biotransformation↗
PubMed1988

In-vitro and in-vivo bacterocodal interactions of clindamycin and ceftazidime, by non-beta-lactamase mechanisms, in experimental Pseudomonas aeruginosa endocarditis caused by a constitutive beta-lactamase overproducing strain.

We studied a ceftazidime-resistant strain of Pseudomonas aeruginosa (PA-48) stably-derepressed for constitutive beta-lactamase overproduction, and its ceftazidime-susceptible parent (PA-96) in order to characterize the ability of clindamycin to: (1) enhance the in-vitro and in-vivo bactericidal activities of ceftazidime for PA-48; and (2) prevent beta-lactamase induction and spontaneous mutation to the derepressed state by the parental strain (PA-96). In vitro, clindamycin synergistically enhanced the bactericidal activity of ceftazidime vs PA-48. In the experimental aortic endocarditis model, the combination of clindamycin with ceftazidime significantly reduced mean intravegetation bacterial densities of PA-48 versus ceftazidime monotherapy and untreated controls at therapy days 6 and 11 (P less than 0.05). Exposure of growing PA-48 cells to clindamycin did not interfere with the hydrolytic function of extracted periplasmic beta-lactamase. Moreover, clindamycin did not suppress cefoxitin-mediated beta-lactamase induction in the parental strain (PA-96). In vitro, clindamycin prevented spontaneous mutation of PA-96 to the stably-derepressed state for beta-lactamase overproduction and also enhanced reversion of derepressed cells of PA-48 to the ceftazidime-susceptible parental phenotype by approximately 2 log10 cfu/ml. This latter effect was mirrored in vivo during clindamycin+ ceftazidime therapy of experimental endocarditis due to strain PA-48, as the proportion of ceftazidime-susceptible cells with vegetations increased by approximately 1-1.5 log10 cfu/g, versus untreated controls or ceftazidime monotherapy recipients. After clindamycin treatment ceased, vegetations contained predominantly ceftazidime-resistant variants. Clindamycin appeared to enhance bactericidal effects of ceftazidime vs PA-48 through non-beta-lactamase mechanisms probably involving promotion and maintenance of spontaneous reversion to the fully-repressed state. However, the concentrations of clindamycin required to achieve these effects are unlikely to be sustained at normal therapeutic dosage.

Animals↗
PubMed1992

Compatibility of ceftazidime and aminophylline admixtures for different methods of intravenous infusion.

OBJECTIVE: Aminophylline and ceftazidime are sometimes used concurrently in patients with respiratory disorders. Parenteral aminophylline usually is administered as a constant infusion, and ceftazidime is given intermittently or less commonly as a constant infusion. We evaluated the stability and compatibility of the two drugs when aminophylline is given as a constant intravenous infusion and ceftazidime is administered simultaneously either through a y-site (piggyback method) or as a continuous infusion (constant infusion method). DESIGN: The chemical stability of intravenous aminophylline and ceftazidime in dextrose 5% and NaCl 0.9% for both methods was studied. Three different formulations of ceftazidime from the same manufacturer were studied (minibag using reconstituted ceftazidime, premixed minibag, and ceftazidime arginine). For the piggyback and constant infusion methods, samples were collected at 0, 1, and 2 hours; and 0, 6, and 24 hours, respectively. All experiments were conducted in triplicate. Samples were analyzed in duplicate by a stability-indicating HPLC assay method. OUTCOME MEASURE: Ceftazidime and aminophylline were considered stable if concentrations remained above 90 percent of the original concentrations over the time periods studied. RESULTS: Ceftazidime was determined to be compatible with aminophylline in the piggyback method. In contrast, when aminophylline and ceftazidime were admixed in the same intravenous container (constant infusion method), the two drugs were not stable. CONCLUSIONS: These data indicate that aminophylline and ceftazidime admixtures are incompatible when prepared in the same intravenous container, which may occur if both are given as a constant infusion. The two drugs are compatible when the ceftazidime is piggybacked into a primary intravenous set in which aminophylline is administered as a constant infusion.

Aminophylline↗
PubMed2000

Pharmacokinetics of ceftazidime in dogs following subcutaneous administration and continuous infusion and the association with in vitro susceptibility of Pseudomonas aeruginosa.

OBJECTIVE: To determine the pharmacokinetics of ceftazidime following subcutaneous administration and continuous IV infusion to healthy dogs and to determine the minimum inhibitory concentration (MIC) of ceftazidime for clinical isolates of Pseudomonas aeruginosa. ANIMALS: 10 healthy adult dogs. PROCEDURE: MIC of ceftazidime for 101 clinical isolates of P aeruginosa was determined in vitro. Serum concentrations of ceftazidime were determined following subcutaneous administration of ceftazidime (30 mg/kg of body weight) to 5 dogs and continuous IV infusion of ceftazidime (loading dose, 4.4 mg/kg; infusion rate, 4.1 mg/kg/h) for 36 hours to 5 dogs. RESULTS: The MIC of ceftazidime for P aeruginosa was < or = 8 microg/ml; all isolates were considered susceptible. Following SC administration of ceftazidime, mean beta disappearance half-life was 0.8 hours, and mean serum ceftazidime concentration exceeded the MIC for P aeruginosa for only 4.3 hours. Two dogs had gastrointestinal tract effects. Mean serum ceftazidime concentration exceeded 16 microg/ml during continuous IV infusion. None of the dogs developed adverse effects. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of ceftazidime subcutaneously (30 mg/kg, q 4 h) or as a constant IV infusion (loading dose, 4.4 mg/kg; rate, 4.1 mg/kg/h) would maintain serum ceftazidime concentrations above the MIC determined for 101 clinical isolates of P aeruginosa. Use of these dosages may be appropriate for treatment of dogs with infections caused by P aeruginosa.

Animals↗
PubMed1998

Recovery of ceftazidime-resistant Klebsiella pneumoniae from pediatric liver and intestinal transplant recipients.

The purpose of this report was to determine the frequency of colonization and bacteremia with ceftazidime-resistant Klebsiella pneumoniae among pediatric candidates for and recipients of liver (LTx) and/or intestinal (ITx) transplantation. Between January and December 1994, surveillance stool cultures obtained from 51 children on the abdominal transplant service were planted on a selective medium containing 2 microg/ml of ceftazidime. Isolates of K. pneumoniae which grew on the selective medium were screened for extended-spectrum beta-lactamase (ESBL) production by the double-disk synergy test and underwent microdilutional susceptibility testing. Strain relatedness of ceftazidime-resistant K. pneumoniae was analyzed by field inversion gel electrophoresis (FIGE). Sixteen of 51 patients had > or = 1 positive stool cultures for ceftazidime-resistant K. pneumoniae; 9 out of 16 on the first culture obtained 1-23 days (median = 5) after admission. All 9 had been in hospital prior to this admission. Four others were positive on their first culture but were in our hospital for > 1 month at the onset of the study. Three patients became colonized after admission. Colonization with ceftazidime-resistant K. pneumoniae was more frequent among recipients of ITx (including combined LTx-ITx) compared to LTx alone (7/13 vs. 7/32, p<0.05). All of the ceftazidime-resistant isolates recovered from surveillance stool cultures had positive double-disk diffusion tests suggesting the presence of ESBL production as the mechanism of resistance. Ceftazidime resistance was identified in 7/8 episodes of bacteremia due to K. pneumoniae in patients on the abdominal transplant service compared with 0/17 episodes in other children in the Children's Hospital of Pittsburgh during the study. During this same time period, 69/312 clinical isolates of K. pneumoniae evaluated in the hospital laboratory were ceftazidime-resistant; 67/69 came from patients on this service. In none of the 312 isolates was resistance to cefotaxime found in the absence of ceftazidime resistance. Unique clones were identified for 10/19 isolates of ceftazidime-resistant strains of K. pneumoniae analyzed by FIGE. Colonization and bacteremia with ceftazidime-resistant K. pneumoniae were commonly identified among recipients of LTx & ITx at the Children's Hospital of Pittsburgh. The mechanism of resistance appeared to be due to the presence of ESBL production by resistant strains. Although resistant strains were frequently recovered from patients on the abdominal transplant service, recovery of ceftazidime-resistant strains from patients outside of this service was rare even in the intensive care setting.

Adolescent↗
PubMed1985

Treatment of skin, skin structure, bone, and joint infections with ceftazidime.

The collective experience with ceftazidime in the treatment of skin, soft tissue, bone, and joint infections is presented. Patients were treated with dosages ranging between 25 and 150 mg/kg per day for between five and 42 days. A total of 570 patients with skin and skin structure infections were treated with ceftazidime. Comparative studies, using either cefamandole or tobramycin plus ticarcillin as control drugs, included 239 patients. There were 600 evaluable patients in five categories of skin or skin structure infection: 252 patients had cellulitis, 107 had wound infections, 103 had abscesses, 90 had skin ulcers, and 48 had other miscellaneous infections. Bacteriologic etiologies were gram-negative rods in 303 episodes, gram-positive cocci in 241, anaerobes in 14 episodes, and miscellaneous other organisms in 48 episodes. Overall bacteriologic efficacy was 90 percent in ceftazidime-treated infections and 76 percent in control-treated infections. The clinical efficacy of ceftazidime against infections caused by the gram-positive cocci, particularly Staphylococcus species, was surprisingly good (85 percent) and similar to the efficacy achieved in the cefamandole-treated patients (85 percent). The overall clinical efficacy for ceftazidime was 93 percent. One hundred thirty-four patients with bone or joint infections received ceftazidime. The dosages were similar, but the duration of treatment was the longest in this group. Ceftazidime treatment was compared with standard dosages of tobramycin and ticarcillin in 11 patients. Osteomyelitis was cured in 58 of the 101 patients who received ceftazidime. In five patients, osteomyelitis failed to respond: in two, a resistant Pseudomonas strain emerged; the other three failures were due to persistent bone sequestra. Thirty-eight patients showed improvement. Of those in the tobramycin and ticarcillin group, nine of 10 evaluable patients (90 percent) showed either cure or improvement. The one failure was due to a persistent sequestrum. Thirteen patients with septic arthritis and seven with bursitis were also treated with ceftazidime; the overall cure rate was 75 percent. Adverse reactions to ceftazidime were severe, and the drug was discontinued in 13 of 570 (2.3 percent) patients with skin or skin structure infections and in five of 134 (3.7 percent) patients with bone and joint infections. These data suggest that ceftazidime is effective as monotherapy in the treatment of skin, skin structure, bone, and joint infections, and that it may be more efficacious against staphylococcal infections than predicted from in vitro data.

Abscess↗
PubMed1990

Pefloxacin versus ceftazidime in therapy of soft tissue infections in compromised patients.

Soft tissue infections in compromised patients are frequently caused by Gram-negative organisms and particularly by Pseudomonas aeruginosa. These pathogens are effectively eradicated by pefloxacin as well as by ceftazidime. The effectiveness and safety of these two agents were compared in a prospective randomized study in 67 patients with soft tissue infections. Underlying conditions included malignant diseases, diabetes mellitus and chronic renal failure. The infections included: post operative infection, septic foot, soft tissue abscess and cellulitis. Thirty-three patients were treated with intravenous ceftazidime for a mean duration of ten days. More than half the 34 patients given pefloxacin were treated only orally for a mean period of 13 days. The clinical and bacteriological outcomes were similar in both groups. There was clinical cure or improvement in 26 pefloxacin cases and in 23 ceftazidime cases, failure in six pefloxacin cases and in seven ceftazidime and relapse in two pefloxacin and in three ceftazidime patients. The bacteriological responses were eradication in 23 pefloxacin cases and in 22 ceftazidime cases, persistence in five pefloxacin cases and in six ceftazidime cases, relapse in one pefloxacin case and in none of the ceftazidime group, reinfection in four pefloxacin cases and in three ceftazidime cases and there was one unassessed patient in the pefloxacin group and two in the ceftazidime group. Nausea and vomiting occurred in three patients and elevation of liver enzymes in another patient; all side effects were observed only in the pefloxacin treated patients. These results suggest that oral pefloxacin could offer an alternative to intravenous ceftazidime in half the compromised patients with tissue infections. However, adverse reactions due to pefloxacin administration should be watched for during such therapy.

Administration, Oral↗
PubMed2002

Cefepime versus ceftazidime as empiric monotherapy for fever and neutropenia in children with cancer.

BACKGROUND: Monotherapy with cefepime or ceftazidime is an effective alternative to combination therapy for the treatment of febrile neutropenic adult cancer patients. We compared the efficacy and safety of cefepime and ceftazidime as empiric monotherapy of febrile neutropenia in children with cancer. MATERIALS AND METHODS: A prospective, open label, randomized, comparative study in pediatric cancer patients was conducted at Chang Gung Children's Hospital from January 1, 2000, to April 15, 2001. Patients with fever and neutropenia (absolute neutrophil count of < or = 500/mm3) were randomized to receive either intravenous cefepime or ceftazidime (50 mg/kg/dose as two or three doses daily). Febrile episodes were classified as microbiologically documented infection, clinically documented infection or unexplained fever. Clinical response to therapy was classified as success and failure. RESULTS: Ninety-five pediatric cancer patients with 120 febrile neutropenic episodes were randomized to receive empiric treatment with cefepime or ceftazidime. After 72 h of treatment, 82.8% (48 of 58) of the eligible patients in the cefepime group continued with unmodified therapy, compared with 87.9% (51 of 58) in the ceftazidime group. The neutrophil count was <100/mm3 at randomization for 76% of the patients in the cefepime group and 83% of those in the ceftazidime group; the median durations of neutropenia (<500/mm3) were 8.5 and 6.5 days, respectively. Of the 96 evaluable episodes the overall success rate with unmodified empiric therapy until the end of the treatment course in the cefepime group was comparable with that in the ceftazidime group (69% vs. 71%, P = 0.95). The response rate after glycopeptides were added to the regimens was 79.2% for the cefepime group and 77.1% for the ceftazidime group. The bacterial eradication rate was 33% for the cefepime group and 20% for the ceftazidime group (P = 0.85), and the rates of new infections were 10.4% vs. 4.2% (P = 0.67), respectively. Both study drugs were well-tolerated. Three (6.4%) patients in the cefepime group and 2 (4.3%) patients in the ceftazidime group died. CONCLUSION: Cefepime appeared to be as effective and safe as ceftazidime for empiric treatment of febrile episodes in neutropenic pediatric cancer patients.

Adolescent↗
PubMed2000

Determinants of ceftazidime clearance by continuous venovenous hemofiltration and continuous venovenous hemodialysis.

Although several dosage adjustment regimens have been proposed, there is little quantitative information to guide the initiation of ceftazidime therapy in patients who are receiving continuous renal replacement therapy. To determine the clearance of ceftazidime by continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodialysis (CVVHD), we performed controlled clearance studies with stable hemodialysis patients with three hemofilters: a 0.6-m(2) acrylonitrile copolymer (AN69; Hospal) filter, a 2.1-m(2) polymethylmethacrylate filter (PMMA; Toray) filter and a 0.65-m(2) polysulfone (PS; Fresenius) filter. Subjects received 1,000 mg of ceftazidime intravenously prior to the start of a clearance study. The concentration of ceftazidime in multiple plasma and dialysate or ultrafiltrate samples was determined by high-performance liquid chromatography. The diffusional clearances (CI(diffusion)) and sieving coefficients of ceftazidime were compared by a mixed-model repeated-measures analysis of variance with filter and blood, dialysate inflow, or ultrafiltration rate as the main effect and the patient as a random effect. The fraction of ceftazidime bound to plasma proteins was 17%+/-7% (range, 10 to 25%). The clearances of ceftazidime, urea, and creatinine by CVVHD were essentially constant at blood flow rates of 75 to 250 ml/min for all three filters. Significant linear relationships (P<0.0001) were observed between CI(diffusion) of ceftazidime and clearance of urea for all three filters: AN69 (slope = 0.83), PMMA (slope = 0.89), and PS (slope = 1.03). Ceftazidime clearance was membrane independent during CVVH and CVVHD. CVVH and CVVHD can significantly augment the clearance of ceftazidime. Dosing strategies for initiation of ceftazidime therapy in patients receiving CVVH and CVVHD are proposed.

Adolescent↗
PubMedDate not supplied

Pharmacokinetics of ceftazidime in CAPD-related peritonitis.

OBJECTIVE: The aim of this study was to measure and evaluate the appropriateness of the actual concentrations of serum and dialysate ceftazidime in Thai continuous ambulatory peritoneal dialysis (CAPD) patients. DESIGN: Prospective and descriptive study of patients treated following the International Society for Peritoneal Dialysis (ISPD) 2000 recommendation for the empiric therapy of CAPD-related peritonitis. SETTING: Institutional level of clinical care. PATIENTS: CAPD-related peritonitis patients were diagnosed by dialysate effluent white blood cell count of more than 100/mm3 and polymorphonuclear leukocytes of at least 50%. There were 10 patients, all at least 18 years of age, entered; all completed the study. INTERVENTION: In accordance with the ISPD 2000 recommendations, the antibiotic regimen comprised continuous intraperitoneal (i.p.) cefazolin and once-daily i.p. ceftazidime. Cefazolin was administered as loading and continuous maintenance doses of 500 and 125 mg/L dialysate respectively. Ceftazidime (20 mg/kg body weight) was given i.p. once daily. Duration of treatment was 96 hours. MAIN OUTCOME MEASURES: Serum and dialysate effluent samples of the 10 CAPD patients with peritonitis were measured for ceftazidime levels, which were used for the development of pharmacokinetic equations that could predict drug concentrations at any treatment time. RESULTS: Following ceftazidime administration as in the ISPD 2000 recommendation, serum ceftazidime levels were above 8 microg/mL, the minimum inhibitory concentration (MIC) recommended by NCCLS, throughout 24 hours. Dialysate ceftazidime levels were below the MIC for total periods of 4.19 and 6.26 hours in day 1 and day 4 respectively. The clinical response rate to the empiric regimen was 90%. CONCLUSIONS: Once-daily i.p. administration of ceftazidime according to the ISPD 2000 recommendation could not provide adequately therapeutic levels of ceftazidime in dialysate throughout 24 hours. Despite this finding and the poor post-antibiotic property of ceftazidime, the empiric regimen including once-daily i.p. ceftazidime could yield good clinical outcome.

Anti-Bacterial Agents↗
PubMed1987

[Results of several different controlled studies with ceftazidime in the treatment of infections in immunosuppressed patients].

At our Division of Hematology eight clinical studies were performed using ceftazidime alone or in combination with other antibiotics. In the first randomised study ceftazidime (45 patients) proved to be statistically superior (p less than or equal to 0.05) to the combination of cefotaxime and gentamicin (45 patients). The poor results of the latter combination - 49% clinical responses compared with 71% for ceftazidime - have been confirmed by the EORTC study group of Klastersky (1). The second study aimed at 30 patients who failed to respond to cefotaxime and gentamicin. All bacteriologically documented infections were cured with ceftazidime. The clinical response rate was 73%. In the third randomised study we compared ceftazidime plus flucloxacillin in 49 patients in order to extend the spectrum to resistant staphylococci with a ceftazidime monotherapy (51 patients). The addition of flucloxacillin did not improve the results substantially. The overall clinical response rate was 81% with the combination and 85% with ceftazidime alone. In the fourth study on 23 patients with allogenic bone marrow transplantations, receiving cyclosporin A as prophylaxis against graft versus host disease, no nephrotoxic effect was observed. The fifth study comprised 20 patients over 65 years of age, in whom no toxicity different from younger patients was seen. In the sixth study with 51 patients per group we compared ceftazidime with the combination ceftazidime plus cephalothin. This study demonstrated an increased efficacy of the combination against Staphylococcus epidermidis and proved that two different cephalosporins, given simultaneously, are not antagonistic. Analysis of 34 Pseudomonas septicaemias in the seventh study with a clinical success rate of 94% demonstrated clearly the potency of ceftazidime against this particularly dangerous organism.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗