Disease relevance of Fortaz

• Of 550 evaluable episodes of fever and neutropenia, 282 were treated with ceftazidime alone and 268 with the combination [1].
• RESULTS: Between November 1990 and October 1992, 55 hospital patients infected or colonized with ceftazidime-resistant E coli, K pneumoniae, or both were identified [2].
• MAIN OUTCOME MEASURE: Incidence of patient infection or colonization by ceftazidime-resistant Klebsiella during 1995 (control period) compared with 1996 (intervention period) [3].
• 11 of 12 infected patients who had malignant disease or were otherwise immunocompromised responded satisfactorily to ceftazidime; 7 of these 12 had infections caused by Pseudomonas aeruginosa [4].
• Photosensitivity due to ambulatory intravenous ceftazidime in cystic fibrosis patient [5].

Psychiatry related information on Fortaz

• Both resistant variants were stably derepressed for the type Id beta-lactamase, which was ceftazidime inducible in the parental strain (PA-96) used to initially infect the rabbits [6].
• Ceftazidime encephalopathy: absence status and toxic hallucinations [7].
• Effect of physical activity on the pharmacokinetics of ceftazidime in mice [8].
• Neurotoxicity has rarely been associated with the drug; however, two of our patients developed ceftazidime-induced neurotoxicity that produced confusion, disorientation, agitation, generalized weakness, and myoclonus [9].

High impact information on Fortaz

• MAIN OUTCOME MEASURES: Clinical and epidemiological factors associated with colonization or infection by ceftazidime-resistant E coli or K pneumoniae; molecular genetic characteristics of plasmid-mediated ceftazidime resistance [2].
• Eligible patients were randomly assigned to receive the antibiotics ceftazidime and amikacin, with or without G-CSF (5 microg/kg per day) [10].
• Isolates were cultured from the sputum of 65 children colonised with ceftazidime-resistant P aeruginosa [11].
• We observed that a high proportion of children attending our CF clinic were colonised with P aeruginosa that was resistant to ceftazidime and other beta-lactam antibiotics [11].
• Efficacy of ceftazidime in chronic melioidosis with multiple liver abscesses [12].

Chemical compound and disease context of Fortaz

• PURPOSE: To compare the efficacy of ceftazidime and imipenem monotherapy for fever and neutropenia, and to determine whether fewer antimicrobial modifications (additions or changes) are required by the broader-spectrum agent, imipenem [13].
• Meropenem versus ceftazidime in the treatment of cancer patients with febrile neutropenia: a randomized, double-blind trial [14].
• A prospective randomized trial of ceftazidime versus netilmicin plus mezlocillin in the empirical therapy of presumed sepsis in cirrhotic patients [15].
• Unlike wild-type (WT) forms, such as the E. cloacae P99 and Citrobacter freundii enzymes, the ES GC1 beta-lactamase is able to rapidly hydrolyze third-generation cephalosporins such as cefotaxime and ceftazidime [16].
• In addition, the activity of cefepime against Pseudomonas aeruginosa isolates was essentially equivalent to that of ceftazidime and greater than that of third-generation cephalosporins [17].

Biological context of Fortaz

• Multiple beta-lactam resistance in Enterobacter cloacae following ceftazidime monotherapy [18].
• OBJECTIVE: To describe the epidemiology, antimicrobial susceptibility, and control of widespread ceftazidime-resistant Klebsiella pneumoniae infections in a North American hospital and circumstances that led to delayed detection [19].
• Isolates were obtained from the Clinical Microbiology Laboratory. RESULTS: Four hundred thirty-two isolates of ceftazidime-resistant Klebsiella pneumoniae were recovered during a 19-month study period [19].
• Natural variants of TEM-1 with increased antibiotic resistance have appeared in response to the use of extended-spectrum beta-lactam antibiotics (e.g., ceftazidime) and beta-lactamase inhibitors (e.g., clavulanic acid) [20].
• DNA sequencing identified the residue positions that are critical for ceftazidime hydrolysis [21].

Anatomical context of Fortaz

• In contrast, treatment with ceftazidime did not affect progenitor cell numbers [22].
• Meropenem was significantly more effective than ceftazidime in severely neutropenic (</= 100 cells/microliter) patients (55% v 43%, respectively), bone marrow transplant patients (73% v 27%, respectively), and patients given antibiotic prophylaxis before study entry (71% v 52%, respectively) [14].
• 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) [23].
• Among patients with discernible etiologic agents in samples of cerebrospinal fluid, 11 of 57 (19 percent) ceftazidime-treated patients died, and five of 27 (19 percent) patients treated with the combination died [24].
• Multivariate logistic-regression analysis showed that recovery of the neutrophil count was the most favorable prognostic factor in a patient's response to infection, whereas the presence of gram-positive infection, acute leukemia, pulmonary or enteric infection, and therapy with ceftazidime were unfavorable factors [25].

Associations of Fortaz with other chemical compounds

• Fleroxacin and ceftazidime at concentrations of 1 to 100 micrograms/mL and ciprofloxacin at high concentration (greater than 10 micrograms/mL) either did not affect CSF production by spleen cells or had an inhibitory effect [22].
• Selection and characterization of amino acid substitutions at residues 237-240 of TEM-1 beta-lactamase with altered substrate specificity for aztreonam and ceftazidime [26].
• Variant beta-lactamases that conferred elevated levels of resistance to the cephalosporin ceftazidime were identified in a set of beta-lactamase derivatives previously generated by pentapeptide scanning mutagenesis in which a variable 5-amino acid cassette was introduced randomly in the target protein [27].
• Mutants that were selected for optimal ceftazidime hydrolysis contained a conserved Ala at position 237, a Ser for Gly substitution at position 238, and a Lys for Glu at position 240 [26].
• DESIGN--An audit of third-generation cephalosporin use during a 6-month period shortly after ceftriaxone and ceftazidime were added to the hospital formulary already containing cefotaxime was performed [28].

Gene context of Fortaz

• Among patients with high baseline TNF-alpha levels, there were significant increases in the IL-10/TNF-alpha ratio at both 24 and 48 h over that at admission for the ciprofloxacin group, while no differences were noted in the ceftazidime group [29].
• However, ampD truncation products and ampD from a partially derepressed P. aeruginosa strain resulted in ceftazidime MICs of >256 microg/ml, indicating a role for these gene modifications in derepressed phenotypes [30].
• TEM-7 is a novel broad-spectrum beta-lactamase (Bla), selected in vivo, with a resistance profile similar to that of TEM-1 and TEM-2, but extended to ceftazidime (Caz) and aztreonam [31].
• Induction of dinB transcription mediated by ceftazidime produces an increase in the reversion of a +1 Lac frameshift mutation [32].
• Pulmonary TNF-alpha, IL-beta, and IL-8 concentrations were attenuated in the ceftazidime group compared with those in the placebo group (p < 0.001, p = 0.02, and p = 0.003) [33].

Analytical, diagnostic and therapeutic context of Fortaz

• This was accompanied by a 44.0% reduction in the incidence of ceftazidime-resistant Klebsiella infection and colonization throughout the medical center (P<.01), a 70.9% reduction within all intensive care units (P<.001), and an 87.5% reduction within the surgical intensive care unit (P<.001) [3].
• PATIENTS AND METHODS: Adult and pediatric patients undergoing chemotherapy for solid tumors, leukemias, or lymphomas were randomized to receive open-label ceftazidime or imipenem on presentation with fever and neutropenia [13].
• High-performance liquid chromatography was used to determine the ceftazidime concentrations in the serum and dialysate samples [34].
• Forty-seven percent of streptococcal strains were penicillin resistant and showed a decreased susceptibility to ceftazidime (minimum inhibitory concentration ranged from 1 to 64 microg/mL) [35].
• Disposition and bioavailability of ceftazidime after intraperitoneal administration in patients receiving continuous ambulatory peritoneal dialysis [34].

References