In vitro and in vivo activities of Syn2190, a novel beta-lactamase inhibitor.
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Syn2190, a monobactam derivative containing 1,5-dihydroxy-4-pyridone as the C-3 side chain, is a potent inhibitor of group 1 beta-lactamase. The concentrations of inhibitor needed to reduce the initial rate of hydrolysis of substrate by 50% for Syn2190 against these enzymes were in the range of 0.002 to 0.01 microM. These values were 220- to 850-fold lower than those of tazobactam. Syn2190 showed in vitro synergy with ceftazidime and cefpirome. This synergy was dependent on the concentration of the inhibitor against group 1 beta-lactamase-producing strains, such as Pseudomonas aeruginosa, Enterobacter cloacae, Citrobacter freundii, and Morganella morganii. However, against beta-lactamase-derepressed mutants of P. aeruginosa, the MICs of ceftazidime plus Syn2190 were not affected by the amount of beta-lactamase, and the values were the same for the parent strains. The MICs at which 50% of isolates are inhibited (MIC(50)s) of ceftazidime plus Syn2190 were 2- to 16-fold lower than those of ceftazidime alone for ceftazidime-resistant, clinically isolated gram-negative bacteria. Similarly, the MIC(50)s of cefpirome plus Syn2190 were two- to eightfold lower for cefpirome-resistant clinical isolates. The synergies of Syn2190 plus ceftazidime or cefpirome observed in vitro were also reflected in vivo. Syn2190 improved the efficacies of both cephalosporins in both a murine systemic infection model with cephalosporin-resistant rods and urinary tract infection models with cephalosporin-resistant P. aeruginosa. (+info)
In vitro antibacterial activity of LJC 11,036, an active metabolite of L-084, a new oral carbapenem antibiotic with potent antipneumococcal activity.
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LJC 11,036 is the active metabolite of L-084, a novel oral carbapenem that exhibits potent broad-spectrum activity. Antibacterial activities of LJC 11,036 against clinical isolates from respiratory infections, such as Streptococcus pneumoniae (n = 52), Streptococcus pyogenes (n = 19), Haemophilus influenzae (n = 50), Klebsiella pneumoniae (n = 53), and Moraxella catarrhalis (n = 53), and from urinary-tract infections, such as Escherichia coli (n = 53) (MICs at which 90% of the isolates were inhibited [MIC(90)s], 0.1, +info)
Melioidosis with adrenal gland abscess.
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We report a case of melioidosis with left adrenal gland abscess in a 51-year-old man from Taiwan who traveled to Rangoon, Burma for a four-day tour on July 15, 1997. The patient developed fever and left upper abdominal pain upon returning to Taiwan on July 19, 1997. Ten days after returning to Taiwan, he was admitted to Chang Gung Memorial Hospital in Keelung, Taiwan and blood culture on admission was positive for Burkholderia pseudomallei. Computerized tomography of the abdomen revealed left adrenal gland swelling and suppuration. Treatment with parenteral ceftazidime and cotrimoxazole for three weeks followed by two months of oral cotrimoxazole cured the infection. The patient remained asymptomatic at 12 months follow-up. (+info)
Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis.
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BACKGROUND: In patients with cirrhosis and spontaneous bacterial peritonitis, renal function frequently becomes impaired. This impairment is probably related to a reduction in effective arterial blood volume and is associated with a high mortality rate. We conducted a study to determine whether plasma volume expansion with intravenous albumin prevents renal impairment and reduces mortality in these patients. METHODS: We randomly assigned 126 patients with cirrhosis and spontaneous bacterial peritonitis to treatment with intravenous cefotaxime (63 patients) or cefotaxime and intravenous albumin (63 patients). Cefotaxime was given daily in dosages that varied according to the serum creatinine level, and albumin was given at a dose of 1.5 g per kilogram of body weight at the time of diagnosis, followed by 1 g per kilogram on day 3. Renal impairment was defined as nonreversible deterioration of renal function during hospitalization. RESULTS: The infection resolved in 59 patients in the cefotaxime group (94 percent) and 62 in the cefotaxime-plus-albumin group (98 percent) (P=0.36). Renal impairment developed in 21 patients in the cefotaxime group (33 percent) and 6 in the cefotaxime-plus-albumin group (10 percent) (P=0.002). Eighteen patients (29 percent) in the cefotaxime group died in the hospital, as compared with 6 (10 percent) in the cefotaxime-plus-albumin group (P=0.01); at three months, the mortality rates were 41 percent (a total of 26 deaths) and 22 percent (a total of 14 deaths), respectively (P=0.03). Patients treated with cefotaxime had higher levels of plasma renin activity than those treated with cefotaxime and albumin; patients with renal impairment had the highest values. CONCLUSIONS: In patients with cirrhosis and spontaneous bacterial peritonitis, treatment with intravenous albumin in addition to an antibiotic reduces the incidence of renal impairment and death in comparison with treatment with an antibiotic alone. (+info)
Intestinal absorption of cefixime in rats.
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AIM: To study the intestinal absorption characters of cefixime (Cef) and the factors affecting Cef absorption. METHODS: A rat intestine loop in situ technique was used to investigate the disappearance rate of Cef from the intestine. Cef concentration in the flux was measured by the reversed phase HPLC. RESULTS: Cef was mainly absorbed from the upper part of the intestine. Its disappearance rate was apparently pH-dependent [(5.8 +/- 0.6) nmol.h-1/(g wet tissue) at pH 7.4, (8.9 +/- 1.4) nmol.h-1/(g wet tissue) at pH 5.0, P < 0.05)]. The uptake rate of Cef was curvilinear at 0.01-0.5 mmol.L-1. The values of apparent Kt, Jmax, and Kd were 0.114 mmol, 78.41 nmol.h-1/(g wet tissue), and 43.70 nmol.h-1.mmol-1/(g wet tissue), respectively. Sodium edetate markedly promoted the disappearance rate of Cef from the intestine. CONCLUSION: Cef was transported partly via carrier-mediated transport system and partly via the paracellular transport system. (+info)
Cefamandole: antimicrobial activity in vitro of a new cephalosporin.
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Cefamandole, a new cephalosporin derivative, was found to have a broad spectrum of activity against a cross-section of both gram-positive and gram-negative bacteria isolated from clinical material. Gram-positive cocci, except for Streptococcus faecalis, were very susceptible. Penicillin G-resistant Staphylococcus aureus also was susceptible to cefamandole. Minimal bactericidal concentrations for gram-positive cocci approximated the minimal inhibitory concentrations. Strains of Haemophilus influenzae were very susceptible to the drug. Most strains of Escherichia coli, Klebsiella sp., and Proteus sp. were inhibited by low concentrations. Increasing resistance occurred with larger inocula. Strains of Pseudomonas sp. were resistant to cefamandole. (+info)
Molecular epidemiology of ceftazidime-resistant gram-negative bacilli on inanimate surfaces and their role in cross-transmission during nonoutbreak periods.
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We described the molecular epidemiology of expanded-spectrum cephalosporin-resistant gram-negative bacilli (RGN) recovered from inanimate surfaces. RGN were isolated from 9% of environmental cultures. Numerous species, each with multiple unique strains, were recovered. Epidemiological links between environmental, personnel, and patient strains suggested the exogenous acquisition of RGN from the hospital environment. (+info)
Antimicrobial treatment of an experimental otitis media caused by a beta-lactamase positive isolate of Haemophilus influenzae.
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A gerbil model of otitis media induced by a beta-lactamase producing and non-serotypeable isolate of Haemophilus influenzae was used to assess the in-vivo efficacy of co-amoxiclav and cefuroxime at low (5 mg/kg) and high (20 mg/kg) doses. The MIC of the antibiotics tested against the pathogen was 1 mg/L (1/0.5 mg/L for co-amoxiclav). The organism was inoculated (+/-10(6) cfu) by transbullar challenge directly in the middle ear and antibiotic treatment was commenced 2 h post-inoculation and continued at 8 h intervals for three doses. Only high dose co-amoxiclav significantly reduced the number of culture-positive specimens as compared with untreated animals or with other treatment groups (91.7% as compared with 36.7% for high dose cefuroxime). The results obtained in any treatment group were related to middle ear antibiotic level/MIC. Antibiotic concentrations in the middle ear 90 min after administration were about 10% of serum levels at 15 min, probably related to a slight inflammatory response. Only after high dose co-amoxiclav did the concentration in the middle ear exceed the MIC by a factor of four. In otitis media with effusion, if indicated, antibiotics active in vitro should be administered in high doses and, to avoid side effects, probably in short courses. (+info)