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PubMed1989

Comparison of the safety and efficacy of intravenous ciprofloxacin and intravenous ceftazidime in the treatment of selected infections.

A study was conducted to determine the comparative safety and efficacy of intravenous ciprofloxacin with that of intravenous ceftazidime in the treatment of selected infections. Male and female inpatients 18 years or older had bacterial infections of the blood, skin or skin/structure, intra-abdominal region, lower respiratory tract, or urinary tract (considered complicated) caused by organisms susceptible to both ciprofloxacin and ceftazidime. Patients were randomly assigned to receive either ciprofloxacin 200 mg intravenously every 12 hours or ceftazidime 0.5 to 2 g intravenously every eight to 12 hours. Clinical evaluations were performed daily during therapy and within five to nine days after therapy was complete. For patients with urinary tract infection, urine for culture was obtained during (Day 3 or 4) and after (five to nine days and three to five weeks) therapy. A total of 86 patients were enrolled into the study. Forty-three received ciprofloxacin and 43 received ceftazidime. There were 22 evaluable patients in the ciprofloxacin group with 24 infection sites: skin/skin structure (eight), respiratory tract (nine), blood (two), urinary tract (five). In the ceftazidime group, there were 26 evaluable patients with 29 infection sites: skin/skin structure (15), respiratory tract (nine), blood (three), and urinary tract (two). The mean duration of therapy with ciprofloxacin and ceftazidime was 7.5 days (range, four to 28 days) and 8.4 days (range, three to 25 days), respectively. Bacteriologic eradication of the causative organisms occurred at 17 infection sites (70.8 percent) in the ciprofloxacin-treated patients and 21 infection sites (72.4 percent) in the ceftazidime group. Clinically, resolution or improvement in signs/symptoms was demonstrated in 22 patients (91.7 percent) in the ciprofloxacin group and 26 patients (89.7 percent) in the ceftazidime group. Bacteriologic response (by organism) and overall response were comparable in both groups. All enrolled patients were evaluated for determination of safety. Adverse events considered possibly or probably related to the study drugs were reported in 16 of 43 patients (37.2 percent) in the ciprofloxacin group and four of 43 patients (9.3 percent) in the ceftazidime group. Ciprofloxacin and ceftazidime were equally efficacious in the treatment of selected infections, but ciprofloxacin was associated with a higher incidence of adverse reactions probably or possibly related to drug administration. Further studies with larger sample sizes in selected patient populations will be required to identify differences in efficacy among the two antibiotics.

Adult↗

PubMed1989

Prospective, randomized comparison of sequential intravenous followed by oral ciprofloxacin with intravenous ceftazidime in the treatment of serious infections.

In a prospective, comparative trial, 47 hospitalized patients with serious infections that required parenteral antibiotic therapy were randomly assigned to receive either ciprofloxacin (200 mg every 12 hours intravenously followed by 500 mg every 12 hours orally at a time dependent on the patients' clinical and bacteriologic responses) or ceftazidime (2 g every eight to 12 hours intravenously). All evaluable subjects (39 patients) had documented infections, 23 percent of which were associated with bacteremia. The mean/median duration of intravenous antibiotic use for ciprofloxacin was 7.37/five days and for ceftazidime 9.95/seven days; 63 percent of the ciprofloxacin patients received an additional 17 days of oral therapy with ciprofloxacin, whereas intravenous therapy with ceftazidime was followed by an average of 12 days of an oral regimen in 55 percent of patients. Overall response rates for patients receiving ciprofloxacin and ceftazidime were 76 percent (16 of 21) and 82 percent (18 of 22), respectively. Four out of five bacteremias in each group were successfully treated. Overall, 69 percent of the pathogens were gram-negative aerobes, and 47 percent of the infections involved the urinary tract. Failure of therapy was most often associated with pneumonia (two of five failures with ciprofloxacin and three of four failures with ceftazidime). Adverse effects occurred in approximately 20 percent of patients in each group and were mild and reversible. Superinfections occurred in five of 19 (26 percent) ciprofloxacin recipients and seven of 20 (35 percent) ceftazidime recipients. All fungal superinfections involved the genitourinary tract and occurred most often in association with chronic indwelling catheters. Enterococcal superinfections occurred in both groups (a bacteremic urinary tract infection in a ceftazidime patient and osteomyelitis in a ciprofloxacin patient). Clostridium difficile-associated diarrhea was documented in a ceftazidime recipient. The mean duration of hospitalization following the onset of antibiotic treatment was 10.45 days in the ciprofloxacin group and 12.95 days in the ceftazidime group. Sequential intravenous/oral ciprofloxacin was as safe and effective as intravenous ceftazidime in the treatment of infections due to susceptible gram-positive and gram-negative organisms.

Administration, Oral↗

PubMed2006

Antimicrobial activity of cefepime tested against ceftazidime-resistant Gram-negative clinical strains from North American Hospitals: report from the SENTRY Antimicrobial Surveillance Program (1998-2004).

To assess the effect of ceftazidime resistance on the activity of other antimicrobial agents, 3030 ceftazidime-resistant Gram-negative bacilli (GNB) isolates (of a total of 42061 GNB) were tested against a panel of more than 30 agents. Ceftazidime resistance was observed in 40.3% of Acinetobacter spp., 16.9% of Pseudomonas aeruginosa, and 5.7% of Enterobacteriaceae isolates. The highest rates of ceftazidime resistance among the enteric GNB were observed with Enterobacter spp. (20.9%) >Citrobacter spp. (15.3%) > indole-positive Proteae (10.1%). Overall, 90% of ceftazidime-resistant Enterobacteriaceae and 30% of ceftazidime-resistant P. aeruginosa remained susceptible to the "4th-generation" cephalosporin, cefepime. The activities (% susceptible) of other antimicrobials tested against ceftazidime-resistant Enterobacteriaceae and P. aeruginosa, respectively, were as follows: amikacin, 90% and 88%; ciprofloxacin, 63% and 46%; gentamicin, 59% and 67%, imipenem, 99% and 65%; levofloxacin, 69% and 44%; and piperacillin/tazobactam only 40% and 12%. Ceftazidime-resistant GNB exhibited high rates of resistance to other antimicrobials. Cefepime was very active against ceftazidime-resistant enteric GNB (AmpC enzyme producers), especially Enterobacter spp. (94.3% susceptible), Citrobacter spp. (96.7% susceptible), and indole-positive Proteae (89.6% susceptible), and showed activity similar to that of ceftazidime against all P. aeruginosa and Acinetobacter spp. isolated in North American medical centers. Continued resistances surveillance monitoring will be necessary to assess the effectiveness of widely used broad-spectrum antimicrobials as novel resistance mechanisms emerge.

Anti-Bacterial Agents↗

PubMed1993

International comparative study of cefepime and ceftazidime in the treatment of serious bacterial infections.

In this randomized multicentre study, we compared the safety and efficacy of cefepime, 2.0 g bd i.v., with that of ceftazidime, 2.0 g tid i.v., as initial treatment of adult patients with serious infections of bacterial aetiology. Three hundred and forty-eight patients were entered into the study, 173 received cefepime and 175 ceftazidime. The treatment groups were comparable with respect to demographic characteristics, including the types of infection (cefepime/ceftazidime: urinary tract, 55/72; lower respiratory tract, 83/74; skin and soft tissue, 23/14; septicaemia, 81/81; and others, 15/5). Gram-positive bacteria were identified as pathogens on 86 occasions (cefepime/ceftazidime: 48/41), including 20 Staphylococcus aureus isolates (13/7) and 27 Streptococcus pneumoniae isolates (14/13). Gram-negative bacilli were isolated on 261 occasions (126/135), and included 219 Enterobacteriaceae (cefepime/ceftazidime: 108/111) and 34 strains of Pseudomonas aeruginosa (14/20). An intention-to-treat analysis revealed satisfactory clinical response rates of 80% and 79% for the cefepime and ceftazidime groups, respectively, and bacteriological eradication rates of 85% and 88% for the cefepime and ceftazidime groups, respectively. Of patients with microbiologically documented infections, 86% (84 of 98) treated with cefepime and 87% (94 of 108) treated with ceftazidime responded satisfactorily. Thirty-two patients (19%) treated with cefepime and 26 (15%) treated with ceftazidime died. Thirty-six patients in the cefepime group and 23 in the ceftazidime group experienced adverse events; therapy was discontinued prematurely in four and two patients in the cefepime and ceftazidime groups, respectively. Of the patients experiencing adverse events, 22 (13%) treated with cefepime developed intolerance at the injection site, compared with 11 (6%) treated with ceftazidime (P = 0.045). In conclusion, twice-daily cefepime (2 g bd) is at least as effective as ceftazidime (2 g tid), as initial empirical therapy for serious bacterial infections in non-neutropenic patients.

Adolescent↗

PubMed2002

Pharmacokinetics of ceftazidime in serum and peritoneal exudate during continuous versus intermittent administration to patients with severe intra-abdominal infections.

Ceftazidime demonstrates time-dependent killing, which is maximal at 4 x or 5 x MIC for the organism, consequently continuous infusion (CI) has been proposed to ensure adequate ceftazidime concentrations for the entire course of therapy. Severe intra-abdominal infections (IAIs) require surgical or percutaneous drainage for management, and ceftazidime is frequently prescribed. Cardiovascular or metabolic changes and renal or liver dysfunction may alter drug pharmacokinetics during severe IAIs, and no data exist on concentrations of ceftazidime reached in the peritoneal fluid. The objectives here were to determine the pharmacokinetics of ceftazidime during continuous and intermittent administration in patients with severe IAIs, and to measure the concentrations of ceftazidime in the peritoneal exudate. Eighteen surgical patients with severe IAI and a creatinine clearance of >30 mL/min were studied. A non-randomized pilot study of six patients treated with CI alone was followed by a prospective, randomized comparative study of 12 patients. Pilot study patients received ceftazidime 1 g iv followed by a 4.5 g CI over 24 h. Randomized patients received either ceftazidime continuously as above or 1.5 g tds. Samples for pharmacokinetic analyses were collected on days 2 and 4. Ceftazidime concentrations were determined by high-performance liquid chromatography. CI resulted in a mean serum concentration >40 mg/L and a T> 4 x MIC for most pathogens encountered in severe IAIs for >90% of the course of therapy in both serum and peritoneal exudate. Eight-hourly administration resulted in T> 4 x MIC for most pathogens encountered in severe IAIs for >90% of the dosing interval, but in peritoneal exudate for only 44% of the dosing interval. During CI, AUCs in the peritoneal exudate were c. 60% of the concomitant serum AUCs. In critically ill surgical patients with severe IAIs, CI of ceftazidime resulted in more favourable concentrations in serum and peritoneal exudate than 8-hourly bolus infusion.

Adult↗

PubMed1985

Efficacy of amikacin and ceftazidime in experimental aortic valve endocarditis due to Pseudomonas aeruginosa.

The in vivo efficacies of amikacin, ceftazidime, and their combination were evaluated in experimental aortic valve endocarditis due to Pseudomonas aeruginosa. Eighty catheterized rabbits were infected with a P. aeruginosa strain susceptible to both amikacin and ceftazidime and then received no therapy (controls), amikacin (15 mg/kg per day), ceftazidime (100 mg/kg per day), or amikacin-ceftazidime. Amikacin-ceftazidime significantly lowered vegetation titers of P. aeruginosa at day 7 of therapy versus other regimens (P less than 0.0005). However, by day 14 of therapy, vegetation titers in animals receiving amikacin or ceftazidime regimens or both were not different from those of untreated controls; this was associated with in vivo development of amikacin resistance in most infected vegetations (79%), a phenomenon not seen at day 7 of therapy. Amikacin resistance was unstable in vivo, being undetectable in vegetations examined 5 days after treatment with amikacin had been completed. In contrast, ceftazidime resistance (first noted at day 7 of therapy in 12% of vegetations) persisted after termination of treatment with this agent. These in vivo observations on loss of amikacin resistance and persistence of ceftazidime resistance were mirrored during in vitro passage studies of amikacin- or ceftazidime-resistant P. aeruginosa strains isolated from cardiac vegetations. Amikacin resistance was no longer detectable by passage 5 in antibiotic-free media; however, ceftazidime resistance was stable despite 15 such passages. In vivo development of aminoglycoside-beta-lactam resistances was associated with poor bacteriologic efficacy in this model.

Amikacin↗

PubMed1993

Comparative pharmacokinetics and serum bactericidal activities of SCE-2787 and ceftazidime.

Ceftazidime and the new SCE-2787 are parenteral cephalosporins with a broad antimicrobial spectrum. Pharmacokinetics, serum bactericidal activities, and side effects were investigated in a randomized crossover study. A total of 12 healthy volunteers received a 20-min infusion of 1.5 g of SCE-2787 or 2.0 g of ceftazidime. Serum and urine concentrations were determined by the bioassay method and by high-pressure liquid chromatography (HPLC). The mean (+/- standard deviation) drug concentrations in serum at the end of infusion of SCE-2787 and ceftazidime were 124.4 +/- 23.8 and 233.1 +/- 54.1 mg/liter, respectively. The urine recovery of SCE-2787 was 87.8% +/- 5.5% of dose in 24 h and for ceftazidime was 85.8% +/- 6.3% of dose in 24 h. Metabolites of SCE-2787 could not be detected by HPLC in serum or urine. Pharmacokinetic parameters were calculated both with a noncompartmental analysis and on the basis of an open two-compartment model (drugs are administered into and eliminated from a central compartment only. However, reversible drug distribution from the central space occurs simultaneously into one peripheral space). The area under the concentration time curve from 0 h to infinity of SCE-2787 was 197.9 +/- 25.4 mg.h/liter, and that of ceftazidime was 334.2 +/- 40.0 mg.h/liter. SCE-2787 had a mean terminal half-life in the elimination phase of 109.0 +/- 15.3 min, while that of ceftazidime was 99.0 +/- 13.4 min. The volume of distribution at steady state of SCE-2787 was 17.1 +/- 1.6 liters/70 kg, and that of ceftazidime was 122.9 +/- 1.3 liters/70 kg. The mean residence time of SCE-2787 was 136.4 +/- 15.4 min, and that of ceftazidime was 122.9 +/- 12.7 min. The renal clearance per. 1.73 m2 of SCE-2787 was 103.1 +/- 12.3 ml/min, and that of ceftazidime was 80.6 +/- 13.2 ml/min. The serum bactericidal activities were measured with the microdilution method of Stratton and Reller (L. B. Reller and C. W. Stratton, J. Infect. Dis. 136:196-204, 1977) against 40 clinically isolated strains. One hour after administration, we measured mean reciprocal bactericidal titers of SCE-2787 and ceftazidime, respectively, against Escherichia coli of 388 and 243, against Klebsiella pneumoniae of 395 and 138, against Pseudomonas aeruginosa of 13.0 and 12.7, and against Staphylococcus aureus of 32.2 and 4.0. No severe side effects were observed in this single drug administration.

Adult↗

PubMed1985

Ceftazidime compared with gentamicin and carbenicillin in patients with cystic fibrosis, pulmonary pseudomonas infection, and an exacerbation of respiratory symptoms. British Thoracic Society Research Committee.

An open randomised comparison of a new intravenous cephalosporin, ceftazidime, with the established regimen of gentamicin and carbenicillin was carried out in patients with cystic fibrosis who had persisting pulmonary infection with Pseudomonas species and who developed acute exacerbations of respiratory symptoms. Fifty patients received ceftazidime and 32 gentamicin and carbenicillin. The ceftazidime and gentamicin were given every eight hours and the carbenicillin every six hours. The mean total daily doses were 151 mg/kg for ceftazidime, 6.3 mg/kg for gentamicin and 450 mg/kg for carbenicillin. The mean duration of treatment was 10 days in patients receiving gentamicin and carbenicillin and 12 days in those receiving ceftazidime. Of the patients with pseudomonas in the initial sputum specimen in whom sputum was cultured after treatment, six (26%) of 23 receiving gentamicin and carbenicillin and seven (18%) of 39 receiving ceftazidime had sputum free from pseudomonas at the end of treatment, but recolonisation occurred subsequently. In those receiving ceftazidime all 10 coexisting organisms were eliminated, whereas only four of seven coexisting organisms in patients receiving gentamicin and carbenicillin were eliminated. Overall clinical improvement occurred in 25 (78%) of 32 patients treated with gentamicin and carbenicillin and 48 (96%) of 50 patients treated with ceftazidime. Nineteen (59%) of the patients receiving gentamicin and carbenicillin but only 15 (30%) of those receiving ceftazidime required admission to hospital or intravenous antibiotics, or both, or died during the three months after treatment. Side effects in both groups were similar, mild, and infrequent. Thrombophlebitis occurred in four patients treated with gentamicin and carbenicillin but in no patients treated with ceftazidime.

Adolescent↗

PubMed1989

Intravenous/oral ciprofloxacin versus ceftazidime in the treatment of serious infections.

Seventy-one adult patients with 72 infections were treated, by random selection, with intravenous/oral ciprofloxacin or intravenously administered ceftazidime. Twenty-seven additional patients with 29 infections who were not appropriate for random assignment were treated in an open study with intravenously administered ciprofloxacin only; the latter infections were generally more serious or were caused by ceftazidime-resistant organisms. The most common doses were ciprofloxacin, 200 mg intravenously and 500 mg orally every 12 hours and ceftazidime, 1 to 2 g intravenously every eight to 12 hours. Forty-seven ciprofloxacin-treated infections and 31 ceftazidime-treated infections were evaluable for determination of efficacy. Infections included lower respiratory tract (21 infections), urinary (37 infections), skin/soft tissue (14 infections), bacteremia/endocarditis (four infections), colitis (one infection), and mastoiditis (one infection). Median minimal inhibitory concentrations of ciprofloxacin and ceftazidime were, respectively: for Enterobacteriaceae, Haemophilus influenzae, and Branhamella catarrhalis, no more than 0.06 and no more than 0.25 micrograms/ml; for Pseudomonas aeruginosa, 0.25 and 4 micrograms/ml; for Enterococcus faecalis, 1 and more than 32 micrograms/ml; and for Staphylococcus aureus, 0.25 and 8 micrograms/ml. Ciprofloxacin, 200 mg intravenously, yielded mean serum concentrations 0.5 and eight hours post-intravenous infusion of 2.3 and 0.7 micrograms/ml, respectively. Satisfactory clinical responses were achieved in 17 (81 percent) of 21 patients with intravenous/oral ciprofloxacin, 22 (71 percent) of 31 patients with ceftazidime, and 20 (77 percent) of 26 patients with intravenous ciprofloxacin. The most common treatment failures occurred in complicated skin/soft-tissue infections treated with intravenous/oral ciprofloxacin, complicated urinary tract infections treated with ceftazidime, and necrotizing P. aeruginosa pneumonia treated with intravenous ciprofloxacin; the pneumonia patients all had respiratory failure and had been previously unresponsive to treatment with other appropriate drugs. Serious adverse reactions were observed in three patients, seizures with intravenous ciprofloxacin in two patients, and Clostridium difficile diarrhea with ceftazidime in one patient. We conclude that sequential intravenous/oral ciprofloxacin and ceftazidime were comparable in efficacy and safety; the ability to change from intravenous to oral therapy is a major convenience. Intravenous ciprofloxacin was useful for more serious infections, often caused by ceftazidime-resistant organisms.

Administration, Oral↗

PubMed1989

Randomized, double-blind comparative study of intravenous ciprofloxacin versus ceftazidime in the treatment of serious infections.

We compared intravenously administered ciprofloxacin with ceftazidime in a randomized, double-blind study. Patients received ciprofloxacin 200 mg intravenously every 12 hours or ceftazidime 2 g intravenously every eight hours, with placebo infusions to maintain blinding. Therapy with metronidazole was added for suspected or documented intra-abdominal infection. Thirty-two of the 57 ciprofloxacin-treated patients were evaluable for determination of efficacy and had 41 bacterial isolates from 34 sites. Thirty-six of the 56 ceftazidime patients were evaluable for determination of efficacy and had 41 bacterial isolates from 38 sites. Seven of 35 bacteremic patients had no identifiable primary focus. The most commonly isolated pathogens were Escherichia coli, Streptococcus pneumoniae, Staphylococcus aureus, and Klebsiella pneumoniae. Cure rates and bacteriologic eradication rates were comparable. Nine patients did not improve. Patients with treatment failures in the ciprofloxacin group included a quadriplegic patient with relapse of urinary tract infection with bacteremia (K. pneumoniae). Another patient with bacteremia (Pseudomonas aeruginosa), pneumonia (Proteus vulgaris), and urinary tract infection (P. vulgaris, Providencia sp.) died on the first treatment day. The third patient (S. aureus and Streptococcus pneumoniae pneumonia) had a new aspiration pneumonia develop on the third day; the pneumococcus also persisted. Undrained S. pneumoniae empyema caused the fourth ciprofloxacin treatment failure, and the fifth patient had a relapse of S. aureus pneumonia with bacteremia. One ceftazidime-treated patient died of pneumococcal pneumonia on the first day. Another had persistent Staphylococcus epidermidis and Listeria bacteremia despite 48 hours of treatment. Two other patients had pneumonia (S. aureus and P. aeruginosa, respectively) and completed full courses of ceftazidime therapy without improvement. Five patients had pneumococcal bacteremia; four patients were cured: one of two patients in the ciprofloxacin group and three of three patients in the ceftazidime group. Significant increases in the number of platelets (four patients with ciprofloxacin treatment, one patient with ceftazidime treatment) and declines in the number of platelets (one patient with ciprofloxacin treatment, one patient with ceftazidime treatment) were observed. Intravenously administered ciprofloxacin is comparable with ceftazidime and is a safe and effective antibiotic for the treatment of patients with serious infections, including bacteremia.

Bacterial Infections↗

PubMed1995

Ceftazidime pharmacokinetics in preterm infants: effects of renal function and gestational age.

OBJECTIVE: The objectives of this study were (1) to determine the effects of gestational age on ceftazidime pharmacokinetics in the preterm infant, (2) to relate these effects to changes in glomerular filtration rate (GFR), and (3) to establish appropriate dosage recommendations for preterm infants on day 3 of life. METHODS: Multiple-dose pharmacokinetics of ceftazidime (administered twice daily in a 25 or 50 mg/kg body weight intravenous dose) were evaluated in 136 preterm infants on day 3 of life. Blood samples were collected from an arterial catheter 0, 1/2, 1, 2, 4, 8, and 12 hours after the intravenous dose. An HPLC method was used to determine ceftazidime concentrations in serum. The GFR was studied simultaneously by means of the 24-hour continuous inulin infusion technique. RESULTS: The total body clearance, volume of distribution, and elimination serum half-life of ceftazidime (mean +/- SD) were 55.7 +/- 34.4 ml/hr (37.3 +/- 11.9 ml/hr/kg), 496 +/- 228 ml (350 +/- 96 ml/kg), and 6.95 +/- 2.32 hours, respectively. The mean +/- SD peak and trough levels were 114.9 +/- 39.4 and 33.9 +/- 17.8 mg/L. All infants had a serum trough level above 5 mg/L. Clearance and volume of distribution of ceftazidime and GFR increased significantly with increasing gestational age, whereas serum trough levels and serum half-life of ceftazidime decreased significantly with increasing gestational age. Ceftazidime clearance increased significantly with increasing GFR. Prenatal exposure to indomethacin resulted in significantly lower GFR values and ceftazidime clearances. CONCLUSIONS: Dosage recommendations for ceftazidime administration in preterm infants during the first week of life should be based on gestational age and GFR. Additional adjustments in dosage are indicated in preterm infants who are exposed prenatally to indomethacin.

Ceftazidime↗

PubMed1998

Continuous infusion of ceftazidime with an elastomeric infusion device.

The serum disposition, antimicrobial activity, and stability of ceftazidime continuously infused with an elastomeric infusion device (Homepump, Block Medical) were studied. Twelve healthy adult volunteers were given a 500-mg bolus dose of ceftazidime infused i.v. over two minutes, followed by a continuous i.v. infusion of 3 g over 24 hours. Blood samples were drawn five minutes before and at intervals up to 24 hours after the start of the bolus infusion. Samples were collected from the infusers immediately before and at the end of the 24-hour infusion. Infusers were insulated with ice packs. Ceftazidime concentrations were determined by high-performance liquid chromatography. Minimum inhibitory concentrations (MICs), serum inhibitory titers (SITs), and serum bactericidal titers (SBTs) were determined by the microdilution technique. Mean +/- S.D. serum ceftazidime concentrations ranged from 39.50 +/- 6.92 micrograms/ml at peak (30 minutes after the start of the bolus infusion) to 15.30 +/- 2.83 micrograms/mL at trough (24 hours after the start). The ceftazidime MIC for Pseudomonas aeruginosa was 1 microgram/mL; this MIC was exceeded 100% of the time. Serum ceftazidime concentrations achieved a median SIT and SBT of 1:32 and 1:16, respectively, at 30 minutes and 1:8 and 1:8, respectively, at 24 hours. Six infusers met or exceeded the 24-hour infusion time; ceftazidime was stable in these infusers. A 500-mg i.v. bolus of ceftazidime followed by a continuous infusion (3 g over 24 hours) delivered by an elastomeric infusion device produced serum drug concentrations that were constantly above the MIC for P. aeruginosa and maintained serum bactericidal activity against that organism. Adequate stability of ceftazidime was ensured by placing an ice pack next to the infuser.

Adult↗

PubMed1990

Comparison of pefloxacin with ceftazidime in severe bronchopulmonary infections.

In a prospective open randomized multicentre trial pefloxacin (400 mg twice daily, orally) or ceftazidime (2 g twice daily iv) were given to 82 and 88 patients, respectively, with serious bronchopulmonary infection, defined as: infection occurring in high risk patients, or infection that had failed to respond to previous antimicrobials, or infection by a multiresistant pathogen. An additional nitroimidazole was allowed if the culture demonstrated the presence of anaerobes considered pathogenic. Efficacy analysis was possible in 139 patients, 70 in the ceftazidime group, 69 in the pefloxacin group. In the efficacy population, 93 bacterial strains were isolated in the pefloxacin group and 89 in the ceftazidime group. There were more Streptococcus spp. in the ceftazidime group (21) than in the pefloxacin group (14) (P = 0.06). A successful clinical response was observed in 45 patients give pefloxacin (65.2%) and 51 patients given ceftazidime (72.9%). The difference was not statistically significant. There were two relapses with pefloxacin and six with ceftazidime. In the pefloxacin group 86 pathogens (91%) and in the ceftazidime group 78 pathogens (88%) were eradicated. There were 18 and 13 adverse reactions with ceftazidime and pefloxacin, respectively. In this study, pefloxacin was as effective and as safe as ceftazidime in the treatment of severe bronchopulmonary infections.

Administration, Oral↗

PubMed1999

Piperacillin/tazobactam plus tobramycin versus ceftazidime plus tobramycin for the treatment of patients with nosocomial lower respiratory tract infection. Piperacillin/tazobactam Nosocomial Pneumonia Study Group.

An open-label, randomized, comparative, multi-centre study was conducted at 25 centres in the USA and Canada to compare the safety and efficacy of piperacillin/tazobactam plus tobramycin with ceftazidime plus tobramycin in patients with lower respiratory tract infections. Piperacillin/tazobactam (3 g/375 mg) every 4 h or ceftazidime (2 g) every 8 h were administered i.v. for a minimum of 5 days. Tobramycin (5 mg/kg/day) given in divided doses every 8 h was administered to all patients. Patients with Pseudomonas aeruginosa isolated from respiratory secretions at baseline were to continue tobramycin for the duration of the study. Tobramycin could be discontinued in other patients after the baseline culture results were known. A total of 300 patients was randomized, 155 into the piperacillin/tazobactam group and 145 into the ceftazidime group. Of these, 136 patients (78 in the piperacillin/tazobactam group and 58 in the ceftazidime group) were considered clinically evaluable. Both groups were comparable for age, sex, duration of treatment and other demographic features. The clinical success rate in evaluable patients was significantly greater (P = 0.006) in the piperacillin/tazobactam treatment group (58/78; 74%) than in the ceftazidime group (29/58; 50%). Eradication of the baseline pathogen was significantly greater (P = 0.003) in the piperacillin/tazobactam group (66%) than in the ceftazidime group (38%). The clinical and bacteriological responses of those patients with nosocomial pneumonia were similar to the overall results. Twelve (7.7%) piperacillin/tazobactam-treated patients and 24 (17%) ceftazidime-treated patients died during the study (P = 0.03). Seven of the 24 deaths in the ceftazidime treatment group but only one of the 12 deaths in the piperacillin/tazobactam treatment group were directly related to failure to control infection. The majority of adverse events were thought by the investigator to be attributable to the patients' underlying disease and not drug related. In this study, piperacillin/tazobactam plus tobramycin was shown to be more effective and as safe as ceftazidime plus tobramycin in the treatment of patients with nosocomial LRTI.

Adolescent↗

PubMed2004

A novel extended-spectrum beta-lactamase CTX-M-23 with a P167T substitution in the active-site omega loop associated with ceftazidime resistance.

OBJECTIVE: In recent years, cefotaximases of the CTX-M type have become a predominant cause of resistance to extended-spectrum cephalosporins in Gram-negative bacteria. Although most enzymes provide higher levels of resistance to cefotaxime than to ceftazidime, mutants with enhanced catalytic efficiency against ceftazidime have recently been described. This report identifies another ceftazidime-resistant mutant of the CTX-M class of enzymes. METHODS: Two ceftazidime-resistant strains, Escherichia coli IFI-1 and Klebsiella pneumoniae IFI-2, were isolated from a 46-year-old man during treatment of postoperative peritonitis with ceftazidime. Susceptibility testing, mating-out assays, isoelectric focusing as well as PCR and sequencing techniques were carried out to investigate the underlying mechanism of resistance. RESULTS: E. coli IFI-1 and K. pneumoniae IFI-2 exhibited a clavulanic acid-inhibited substrate profile that included extended-spectrum cephalosporins. Notably, both strains had up to a 32-fold higher level of resistance to ceftazidime than to cefotaxime. Further characterization revealed that a novel bla(CTX-M) gene encoding a beta-lactamase with a pI of 8.9 was implicated in this resistance: CTX-M-23. Along with the substitutions D114N and S140A, CTX-M-23 differed from CTX-M-1, the most closely related enzyme, by a P167T replacement in the active-site omega loop, which has not previously been observed in other CTX-M enzymes. By analogy with what was observed with certain TEM/PSE/BPS-type beta-lactamases, the amino acid substitution in the omega loop may explain ceftazidime resistance, which has only rarely been reported for other CTX-M enzymes. CONCLUSION: The emergence of a new ceftazidime-resistant CTX-M-type mutant provides evidence that these enzymes are able to broaden their substrate spectrum towards ceftazidime, probably due to substitutions in the active-site omega loop.

Amino Acid Sequence↗

PubMed1981

Comparative multiple-dose pharmacokinetics of cefotaxime, moxalactam, and ceftazidime.

The pharmacokinetics of cefotaxime, moxalactam, and ceftazidime were investigated in six human volunteers who received in a crossover fashion doses of 0.5, 1.0, and 2.0 g of each drug by a 5-min infusion. Doses of 1.0 g were repeated after the administration of probenecid. Serum and urine concentrations were assayed with an agar diffusion method. Serum concentrations of moxalactam exceeded those of ceftazidime at all times and were distinctly higher than those of cefotaxime. The normalized area under the concentration time curve (defined as the ratio of the area under the curve per dose) reflects this relationship: compared with cefotaxime the normalized area under the curve of moxalactam was 3 to 4 times higher, and that of ceftazidime was 2 to 3 times higher. By intra-individual comparisons, the area under the curve of moxalactam was 44% larger than that of ceftazidime. With increasing doses, cefotaxime exhibited a nonlinear increase of the area under the curve. The half-lives of moxalactam, ceftazidime, and cefotaxime were 2.34, 1.95, and 1.16 h, respectively. The volume of distribution averaged 0.20 +/- 0.03, 0.23 +/- 0.02, and 0.25 +/- 0.04 liters per kg, and the mean total body clearance was 84, 131, and 328 ml/min for moxalactam, ceftazidime, and cefotaxime, respectively. The 24-h urinary recovery was highest for moxalactam (75 +/- 4%) followed by ceftazidime (68 +/- 11%) and cefotaxime (53 +/- 6%). The influence of probenecid on serum concentrations, half-life, area under the curve, and clearance was most apparent with cefotaxime, whereas the pharmacokinetics of moxalactam and ceftazidime were only slightly affected. After the 0.5- and 2.0- g doses of cefotaxime, desacetyl-cefotaxime activity (determined by high-pressure liquid chromatography) reached a peak of 2.7 and 9.9 mug/ml and declined with a half-life of 1.9 and 1.4 h. The ratio of the R(-) and S(-) epimers of moxalactam, which could be differentiated by high-pressure liquid chromatography, fell rapidly from 0.81 at 0.17 h to 0.5 at 5 h, indicating the presence of twice as much of the microbiologically less active S(-) epimer. From a pharmacokinetic standpoint it appears reasonable to conclude that moxalactam and possibly ceftazidime could be administered twice daily and that cefotaxime could be administered three or even four times daily.

Cefotaxime↗

PubMed1986

Randomized comparison between two ceftazidime-containing regimens and cephalothin-gentamicin-carbenicillin in febrile granulocytopenic cancer patients.

Because the results of our published trial [R. Ramphal, B. S. Kramer, K. H. Rand, R. S. Weiner, and J. W. Shands, Jr., J. Antimicrob. Chemother. 12(Suppl. A):81-88, 1983] of ceftazidime versus cephalothin, gentamicin, and carbenicillin (KGC) revealed a preponderance of gram-positive superinfections, including those caused by clostridia, in patients treated with ceftazidime, we added vancomycin to the ceftazidime regimen at study entry 49 and continued with a 2:1 randomized comparison of ceftazidime-vancomycin (CV) versus KGC. Criteria for study entry were fever (temperature, greater than or equal to 38.5 degrees C on one occasion or greater than or equal to 38 degrees C on two occasions 6 h apart) and granulocytopenia (less than 500/mm3 or a falling count anticipated to be less than 500/mm3). Ninety-five entries (79 patients) were evaluable. The numbers of initial clinical responses for ceftazidime-, KGC-, and CV-treated patients were 9 of 21 (43%), 21 of 37 (57%), and 21 of 37 (57%), respectively; differences were not significant. The death rate was lower with CV (2 of 37 patients) than with KGC (10 of 37 patients) (P less than 0.05 by two-tailed analysis) or with ceftazidime alone (7 of 21 patients) (P less than 0.025). Death from presumed infections occurred in 9 of 37 KGC-treated patients versus 1 of 37 CV-treated patients (P less than 0.025). Superinfections occurred in five ceftazidime-treated patients (24%) versus 7 KGC-treated patients (19%) but not in CV-treated patients (CV versus KGC, P less than 0.05; CV versus ceftazidime, P less than 0.01). CV appears to be superior to KGC or ceftazidime alone in the management of febrile granulocytopenic cancer patients.

Adult↗

PubMed1993

Efficacy of ceftazidime and aztreonam alone or in combination with amikacin in experimental left-sided Pseudomonas aeruginosa endocarditis.

The in vivo efficacies of ceftazidime, aztreonam, and the combinations of ceftazidime with amikacin and aztreonam with amikacin were studied in the rabbit left-sided endocarditis model by using two strains of Pseudomonas aeruginosa, one multisusceptible and one multiresistant, in a total of 156 animals. Antibiotics were given intramuscularly for 10 days, as follows: amikacin, 7 mg/kg of body weight every 8 h, and ceftazidime and aztreonam, 50 mg/kg every 8 h. All regimens except amikacin alone significantly reduced the number of CFU per gram of vegetation (P < or = 0.008), but only for the multisusceptible strain for which sterile vegetations were obtained in 20, 25, 21, 75, and 53% of the groups treated with amikacin, ceftazidime, aztreonam, and the combination groups ceftazidime-amikacin and aztreonam-amikacin, respectively (ceftazidime plus amikacin versus controls, P = 0.001). Regarding the decrease in the numbers of colonies in vegetations, (i) all regimens significantly reduced the number of CFU per gram of vegetation (P < 0.001), (ii) results with ceftazidime-amikacin compared with those with monotherapy were significantly different (P < or = 0.007), and (iii) results with aztreonam-amikacin, although better than those with monotherapy, were marginally not statistically significant. At 1 h postdose, mean amikacin, aztreonam, and ceftazidime levels in serum were 35 +/- 19.4, 89.6 +/- 8.16, and 92.61 +/- 11.52 micrograms/ml, respectively. It was concluded that the combination of ceftazidime, and possibly aztreonam, with amikacin given at high doses and short intervals could have a place in the therapy of patients with left-sided endocarditis caused by P. aeruginosa.

Amikacin↗