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In vitro activity of fosfomycin-gentamicin, fosfomycin-ceftazidime, fosfomycin-imipenem and ceftazidime-gentamicin combinations against ceftazidime-resistant Pseudomonas aeruginosa.

The effects of antimicrobial combinations against ceftazidime-resistant Pseudomonas aeruginosa strains isolated from hospitalized patients were investigated. Using the checkerboard titration method, combination of fosfomycin-gentamicin, fosfomycin-ceftazidime, fosfomycin-imipenem and ceftazidime-gentamicin was synergistic against 4, 11, 38 and 39% of 22, 18, 29 and 18 strains tested respectively and additive effect of the combinations against the strains tested was 41, 33, 14 and 44%, respectively. Antagonistic effects against the isolates were noted when fosfomycin was combined with gentamicin (27%), ceftazidime (22%) and imipenem (7%). No antagonistic effect was observed in the ceftazidime-gentamicin combination.

Anti-Bacterial Agents↗

Randomized prospective study of ceftazidime versus ceftazidime plus cephalothin in empiric treatment of febrile episodes in severely neutropenic patients.

In a prospective randomized study, ceftazidime monotherapy was compared with a combination of ceftazidime plus cephalothin in 102 febrile neutropenic patients. Thirty bacteriologically documented infections, of which 23 were bacteremias, in 48 clinically assessable patients were treated with ceftazidime alone. Twenty-four bacteriologically proven infections, of which 18 were bacteremias, in 42 clinically assessable patients were treated with a combination of ceftazidime and cephalothin. The clinical response rates in assessable patients were 77% for ceftazidime monotherapy and 88% for the combination. The bacteriological clearance rate was 70% for ceftazidime monotherapy and 79% for the combination. Efficacy against gram-negative pathogens appeared to be excellent, with 93% clearance for ceftazidime monotherapy and 100% clearance for the combination. The bacteriological clearance of gram-positive infections was only 60% for both regimens, with failures mainly due to Streptococcus faecalis and Streptococcus sanguis, which are primarily resistant to both ceftazidime and cephalothin. After addition of vancomycin to those infections which did not respond to empiric therapy, bacteriological clearance rates of 94% (ceftazidime plus vancomycin) and 90% (ceftazidime and cephalothin plus vancomycin) were achieved. Three superinfections were registered in the ceftazidime group and two were seen in the combination group. Other adverse effects of ceftazidime were minimal and were not enhanced by combination with cephalothin. It is concluded that ceftazidime is an effective drug for the empiric treatment of febrile neutropenic patients, especially if one is prepared to modify therapy if resistant gram-positive strains or mycotic infections are encountered. Neither the clinical nor bacteriological cure rates could be substantially improved by adding cephalothin to ceftazidime in initial empiric treatment of febrile neutropenic patients.

Adolescent↗

A randomized prospective study of ceftazidime versus ceftazidime plus flucloxacillin in the empiric treatment of febrile episodes in severely neutropenic patients.

In a prospective, randomized study, ceftazidime monotherapy was compared with a combination of ceftazidime and flucloxacillin in 100 febrile neutropenic patients. Thirty-four bacteriologically documented infections, of which 26 were bacteremias, in 51 patients were treated with ceftazidime alone. Thirty-four bacteriologically proven infections, of which 29 were bacteremias, in 49 patients were treated with a combination of ceftazidime and flucloxacillin. The clinical response rate for ceftazidime monotherapy was 80%; the bacteriological cure rate was 90%. Efficacy against gram-negative pathogens appeared to be excellent, achieving a 100% cure rate. The clinical response and bacteriological cure rates for the combination were 76 and 86%, respectively. Three superinfections were registered in the ceftazidime group, and four, involving six pathogens, were registered in the combination group. Other side effects of ceftazidime were minimal. It is concluded that ceftazidime is an effective drug for the empiric treatment of febrile neutropenic patients. It offers the opportunity to avoid the aminoglycosides in first-line treatment. It may be appropriate to combine ceftazidime with cephalothin or vancomycin or to modify therapy if resistant gram-positive strains are encountered.

Adult↗

Ceftazidime versus ceftazidime plus tobramycin in febrile neutropenic children.

Although the effectiveness of antibiotic monotherapy in febrile neutropenic patients remains unproven, ceftazidime has been shown previously to be effective monotherapy for the empiric treatment of selective patients. The efficacy and safety of ceftazidime versus ceftazidime plus tobramycin was evaluated in the treatment of febrile children (range 8 months to 18 years) with neutropenia secondary to cancer chemotherapeutic agents. Of the evaluable 89 patients, 45 received ceftazidime and 44 received ceftazidime plus tobramycin for 5 to 10 days. At the end of therapy, 30 (67%) of the 45 ceftazidime-treated patients were clinically cured compared with 38 (86%) of 44 combination-treated patients. Thirteen (29%) of the patients treated with ceftazidime failed to respond clinically to treatment, versus four (9%) of the patients treated with ceftazidime/tobramycin (p = 0.046). This study suggests that ceftazidime as monotherapy in febrile neutropenic children may be inferior to combination therapy for optimal clinical response in these patients.

Adolescent↗

Ceftazidime plus teicoplanin versus ceftazidime plus amikacin as empiric therapy for fever in cancer patients with granulocytopenia.

In a prospective randomized study, 100 episodes of fever (greater than 38 degrees C) and granulocytopenia (less than 1000/microliters) in cancer patients were empirically treated with ceftazidime (2 g every 8 h) plus teicoplanin (400 mg every 8 h on day 1; 400 mg every day thereafter) or ceftazidime (2 g every 8 h) plus amikacin (500 mg every 8 h). Bacteraemia, clinically documented infection and possible infection were documented in seven, 11 and 19 patients treated with ceftazidime plus teicoplanin and in 11, four and 17 patients treated with ceftazidime plus amikacin. Overall, the response rate was similar in the two groups of patients as was the need for treatment modifications and the rate of death. For documented Gram-positive bacteraemia, the response rate was 2/5 patients treated with ceftazidime plus teicoplanin and 2/7 with ceftazidime plus amikacin; for documented Gram-negative bacteraemia, the response rate was 1/2 and 3/4 patients respectively. No breakthrough bacteraemia was observed. Tolerance was excellent, although renal toxicity (elevation of serum creatinine) was observed in three patients treated with ceftazidime plus teicoplanin and in none allocated to ceftazidime plus amikacin.

Adult↗

Ceftazidime sodium carbonate versus ceftazidime arginine as empirical monotherapy in febrile neutropenic patients.

A prospective randomized trial was conducted to determine the efficacy and safety of ceftazidime sodium carbonate versus a new arginine formulation of ceftazidime as empirical monotherapy in 100 febrile neutropenic patients. The clinical cure rate for ceftazidime sodium carbonate was 91% and for ceftazidime arginine 83%. Forty-two infections could be confirmed bacteriologically. Bacteriological cure rates were 87% and 81% respectively. Only one fatal infection-related outcome occurred during the first three days of therapy (ceftazidime arginine, Corynebacterium parvum). No failures were recorded in bacteriologically proven gram-negative infections. Ceftazidime was confirmed to be safe and effective as empirical monotherapy in febrile neutropenic patients. The arginine formulation is as effective and safe as the sodium carbonate formulation, but easier to handle.

Adolescent↗

A randomized study of ceftazidime compared to ceftazidime and tobramycin for the treatment of infections in cancer patients.

Three hundred and twenty-one febrile episodes in cancer patients were treated with ceftazidime alone or in combination with tobramycin. Patients were grouped according to their neutrophil count into neutropenic and non-neutropenic (less than 1000 and greater than 1000/mm3) respectively. Two hundred and seventy-five episodes were evaluated. The overall response rate in 83 episodes of infection treated with ceftazidime alone was 60 and 73% in those who received the combination. In those bacteriologically proven the response rate was 72% in both groups of the study. The overall response rate in septicaemia was 75% with ceftazidime alone and 85% with the combination. High response rates were obtained in Gram-negative bacillary septicaemias in both groups even in neutropenic patients treated with ceftazidime alone. Pneumonias in neutropenic patients responded equally well. However, patients with adequate neutrophil counts responded better to the combination than to single-agent therapy. The response rate for Gram-positive infections was 41% for ceftazidime alone and 57% for the combination, which was inferior to the results obtained for Gram-negative infections (P = 0.001). The rates of superinfection and toxicity were very low. Ceftazidime is a useful antibiotic against Gram-negative infections in cancer patients. It should be combined with an agent active against Gram-positive pathogens in neutropenic patients.

Adolescent↗

The efficacy and safety of isepamicin and ceftazidime compared with amikacin and ceftazidime in acute lower respiratory tract infection.

Isepamicin is a new aminoglycoside antibiotic which has a superior stability to aminoglycoside-inactivating enzymes compared with other available aminoglycosides. In this multicentre, randomised, open study, the safety and efficacy of isepamicin plus ceftazidime was compared with that of amikacin plus ceftazidime in adults with acute lower respiratory tract infection. Patients with severe infections received intravenous administration of isepamicin 15 mg/kg once daily + ceftazidime 2g twice daily (n = 121) or amikacin 7.5 mg/kg twice daily + ceftazidime 2g twice daily (n = 61). Those with less severe infection received intramuscular or intravenous administration of isepamicin 8 mg/kg once daily + ceftazidime 1g twice daily (n = 56) or amikacin 7.5 mg/kg twice daily + ceftazidime 1g twice daily (n = 28). In the efficacy populations, the proportion of patients clinically cured in the isepamicin group (87/100; 87%) was similar to that in the amikacin group (36/47; 77%). Significantly more patients in the isepamicin group were cured or improved compared with the amikacin group (97% vs 89%; p = 0.042). The difference between treatment groups was also significant in patients with pneumonia (p = 0.05). The most commonly isolated target organisms were Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus and Klebsiella pneumoniae. The proportion of patients in the efficacy population whose pretreatment valid target organisms were eliminated was similar in each treatment group (90% isepamicin vs 89% amikacin). A retrospective analysis showed there were slightly fewer clinical successes and a higher death rate in patients with nosocomial rather than community acquired pneumonia. Both treatments were well tolerated . Fourteen per cent of isepamicin and 11% of amikacin patients experienced adverse events. The incidence of ototoxicity and nephrotoxicity was low.

Acute Disease↗

Two randomized controlled trials of ceftazidime alone versus ceftazidime in combination with trimethoprim-sulfamethoxazole for the treatment of severe melioidosis.

BACKGROUND: Two antibiotic regimens are used commonly in Thailand for the initial treatment of severe melioidosis: ceftazidime in combination with trimethoprim-sulfamethoxazole (TMP-SMX) and ceftazidime monotherapy. It is not known whether TMP-SMX provides an additional benefit. METHODS: Two prospective, randomized trials that compared these regimens for patients presenting with acute severe melioidosis were started independently at tertiary care hospitals in Ubon Ratchathani and Khon Kaen (in northeastern Thailand), and the results were analyzed together as a prospective, individual-patient data meta-analysis. The primary end point was in-hospital mortality rate. RESULTS: The in-hospital mortality rate among all enrolled patients (n=449) was not significantly different between those randomized to ceftazidime alone (25.1%; 56 of 223 subjects) and those randomized to ceftazidime with TMP-SMX (26.6%; 60 of 226 subjects; odds ratio [OR], 1.08; 95% confidence interval [CI], 0.7-1.7; stratified P=.73). Of the 241 patients with culture-confirmed melioidosis, 51 (21.2%) died. Of these 241 patients, 31 (12.9%) died > or =48 h after the time of study entry. Among patients with melioidosis, there was no difference in death rate between the 2 treatment groups for either all deaths (OR, 0.88; 95% CI, 0.48-1.6; stratified P=.70) or for deaths that occurred > or =48 h after hospital admission (OR, 0.88; 95% CI, 0.41-1.9; stratified P=.73). Conditional logistic regression analysis revealed that bacteremia, respiratory failure, and renal failure were independently associated with death and treatment failure. Drug regimens were not associated with death or treatment failure in this model. CONCLUSION: We conclude that the addition of TMP-SMX to ceftazidime therapy during initial treatment of severe melioidosis does not reduce the acute mortality rate.

Adult↗

Studies on a new formulation of ceftazidime--ceftazidime arginine--in patients with recurrent chest infections.

One hundred hospital patients with respiratory infections were treated with 1 or 2 g intramuscular injections of ceftazidime sodium or of a new formulation of ceftazidime with arginine three times daily. Clinical and microbiological assessments showed no significant differences in efficacy between the two preparations. Local pain necessitating lignocaine was noted in five of 49 evaluable patients given ceftazidime sodium (10.2%) but in none of the 50 receiving ceftazidime arginine. No other unwanted effects were recorded. The pharmacokinetic results after the 1 g injections showed slightly higher Cmax values with ceftazidime arginine with correspondingly greater 0-7 h AUC values. The mean AUCs were almost identical after the 2 g injections.

Aged↗

Ceftazidime monotherapy is as effective as ceftazidime combined with gentamicin in the treatment of febrile neutropenic patients.

To evaluate the efficacy of ceftazidime monotherapy in the empirical treatment of febrile neutropenic patients, a randomized trial was performed of ceftazidime (C) vs. ceftazidime and gentamicin (C + G) with the addition of teicoplanin (T) for those patients with a long intravenous line-associated infection. Success without modification at the end of treatment was seen in 32.7% (C), 28.3% (C + G), 52.4% (C + T) and 65.2% (C + G + T). Monotherapy with ceftazidime is as effective as when used in combination with an aminoglycoside in neutropenia.

Agranulocytosis↗

Ceftazidime plus amikacin versus ceftazidime plus vancomycin as empiric therapy in febrile neutropenic children with cancer.

Two antibiotic regimens, ceftazidime plus amikacin and ceftazidime plus vancomycin, were compared in a prospective, randomized clinical trial as empiric therapy in febrile granulocytopenic children with cancer. The rate of response was similar in the two groups (66% vs. 77%). The prevalence of secondary gram-negative bacteremia was higher--but not significantly higher--in the group receiving vancomycin. Adverse reactions also occurred more often in the latter group (35% vs. 4%). Mortality did not differ significantly in the two groups. Adjustment for independent predictors of response to treatment by means of multivariate analysis confirmed the lack of any remarkable difference between the responses to the two regimens. We conclude that the use of vancomycin instead of amikacin in combination with ceftazidime does not significantly improve the outcome of treatment of fever and infection in granulocytopenic children with cancer and that the use of vancomycin is associated with an increased frequency of both secondary infections due to gram-negative bacteria and adverse reactions.

Amikacin↗

Efficacies of cefepime, ceftazidime, and imipenem alone or in combination with amikacin in rats with experimental pneumonia due to ceftazidime-susceptible or -resistant Enterobacter cloacae strains.

The antibacterial activities of human regimens of cefepime, ceftazidime, and imipenem alone or in combination with amikacin against an isogenic pair of Enterobacter cloacae strains (wild type and its corresponding derepressed cephalosporinase mutant) were compared by using our nonlethal model of pneumonia with 180 immunocompetent rats. Compared with untreated animals, all beta-lactam-treated rats, except those inoculated with the mutant isolate and receiving ceftazidime, had significantly lower bacterial counts in their lungs 60 h after the onset of therapy. Although the combination of a beta-lactam and amikacin was more bactericidal than each corresponding antimicrobial agent alone, true synergy was noted only with cefepime and imipenem against the constitutive derepressed strain.

Amikacin↗

Immediate and prolonged clinical efficacy of ceftazidime versus ceftazidime plus tobramycin in chronic Pseudomonas aeruginosa infection in cystic fibrosis.

20 patients with cystic fibrosis and chronic bronchopulmonary infection due to Pseudomonas aeruginosa entered a randomized cross-over study comparing ceftazidime (150 mg/kg body weight/24 h) plus tobramycin (10 mg/kg body weight/24 h) to ceftazidime alone (150 mg/kg body weight/24 h), both given intravenously for 2 weeks. 17 patients completed the study; both treatment regimens improved lung function and decreased the WBC count. No difference in clinical efficacy was found between the treatments. Pulmonary function returned to pre-treatment levels 3 months later with no difference between the treatments. No changes were seen in minimal inhibitory concentrations during treatment. None of the patients developed hypersensitivity or experienced serious adverse reactions to the drugs.

Adult↗

[Prospective randomized controlled study of a ceftazidime and pefloxacin combination versus a ceftazidime and amikacin combination in the empirical treatment of pneumonia and nosocomial septicemia at intensive care units].

Three hundred fifty-two patients from 20 intensive care units, suffering from pneumonia or nosocomial septicemia were treated at random with either ceftazidime + pefloxacin (CP) or ceftazidime + amikacin (CA). After exclusion of patients who did not comply with the protocol and of cases where no organism was isolated, 108 assessable patients received CP and 114 received CA. The cure rates achieved in infections due to a single organism were 82 per cent in the CA group and 62 per cent in the CP group. In infections due to multiple organisms, the cure rate was 67 per cent with both antibiotic regimens.

Amikacin↗

[Controlled randomized prospective study of a ceftazidime-pefloxacin combination versus a ceftazidime-amikacin combination in the empirical treatment of nosocomial pneumonias and septicemias of resuscitation. Preliminary results].

The preliminary results obtained in 212 patients from 20 intensive care units, suffering from pneumonia or nosocomial septicemia and treated at random with either ceftazidime + pefloxacin (CP) or ceftazidime + amikacin (CA) were analyzed. After exclusion of patients who did not comply with the protocol and of cases where no organism was isolated, 57 assessable patients received CP and 72 received CA. The cure rates achieved in infections due to a single organism were 85 per cent in the CA group and 63 per cent in the CP group. In infections due to multiple organisms, the cure rate was 74 +/- 2 per cent with both antibiotic regimens.

Amikacin↗

[A pharmacokinetic and clinical evaluation of ceftazidime in neonates and premature infants. A study of ceftazidime in the perinatal co-research group].

Ceftazidime (CAZ) was evaluated for its pharmacokinetics and clinical usefulness in neonates and premature infants. The results obtained were summarized below. Following intravenous injection of CAZ 10 or 20 mg/kg to neonates and premature infants, dose response was observed in serum concentrations ranging from 5.1 to 21.9 micrograms/ml at 6 hours after the injection. The serum half-life tended to be longer in premature infants than in neonates; the half-life being longer for an infant with lower day-age. Urinary recovery rates during the first 6 hours after single administrations of 10 mg/kg of CAZ tended to be higher in neonates than in premature infants, and higher rates were observed in older infants. However, no noticeable difference was observed after the administration of CAZ 20 mg/kg. Clinical efficacy was evaluated in 99 neonates and 55 premature infants (156 infections), daily doses ranging from 21.1 to 246.4 mg/kg. Out of 105 cases of common infections, mainly 44 cases with causative organisms identified (including 17 of sepsis, 7 of pneumonia, 4 of purulent meningitis, 11 of urinary tract infections) were examined for the clinical efficacy. The efficacy of CAZ was excellent in 21, good in 18, fair in 1 and poor in 4, with the efficacy rate of 88.6%. In the remaining 61 cases, i.e., 37 with causative organisms unknown and 24 with signs of intrauterine infections, the efficacy rate was 95.1%. Other than these cases, additional 51 cases were given CAZ solely for prophylaxis of infections, and the results were found satisfactory. On the whole, clinical efficacy rate of CAZ was 94.9% in 156 cases. Out of the 44 cases examined for bacteriological responses, 38 were evaluated as 'eradicated', 3 'persisted' and 3 'unknown' with eradication rate of 92.7%. Replacement of organisms (superinfection) was observed in 3 cases. Out of 179 cases in which adverse effects were assessable, adverse effects were observed in a total of 4 cases (2.2%), i.e., 3 cases of diarrhea (1.7%) and 1 case of rash (0.6%), and abnormal laboratory findings were observed in a total of 14 cases (7.8%), i.e., increase in eosinophiles count in 8 (4.5%), elevation of GOT in 3 (1.7%), increase in platelet, elevation of GOT . GPT, and elevation of GOT . GPT . BUN in 1 case each (0.6%). None of them were severe and they were transient. Elevations of bilirubin and cases of positive PIVKA II associated with CAZ were not observed.(ABSTRACT TRUNCATED AT 400 WORDS)

Bacterial Infections↗