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PubMed1989

Cefsulodin for the treatment of Pseudomonas infections--a study comparing cefsulodin and ticarcillin.

The efficacy of cefsulodin against infections caused by Pseudomonas aeruginosa was investigated first in an open trial and then in a controlled comparative study in which ticarcillin was used. The first trial consisted of 16 patients with proven Pseudomonas aeruginosa infections, 9 of whom also received an aminoglycoside. In the second trial 28 such patients were evaluated (14 on cefsulodin 1 g 4 times daily and 14 on ticarcillin 5 g 4 times daily); all patients also received an aminoglycoside. The results of the two trials were similar in that 75% of the patients of the first trial and 86% of the second group exhibited an excellent or good response to cefsulodin. For the ticarcillin group a similar response was noted. In the first trial the sensitivity of P. aeruginosa did not change markedly, whereas one strain of the cefsulodin group became resistant in the second trial. Pharmacokinetic data were in agreement with those reported in the literature. Side effects were rare.

Adult↗
PubMed1989

Permeability to cefsulodin of the outer membrane of Pseudomonas aeruginosa and discrimination between beta-lactamase-mediated trapping and hydrolysis as mechanisms of resistance.

A pair of strains of Pseudomonas aeruginosa (3-Pre: cefsulodin-sensitive, inducible beta-lactamase; and 3-Post: cefsulodin-resistant, elevated beta-lactamase, derived from 3-Pre by subculture in the presence of cefsulodin) were taken as representative of the class of bacteria resistant to third-generation cephalosporins due to elevated synthesis of the normally inducible, chromosomally encoded beta-lactamase. These two strains were used to differentiate between 'trapping' and 'hydrolytic' mechanisms of cefsulodin resistance by (a) measuring the outer-membrane permeabilities to cefsulodin, (b) measuring the kinetics of cefsulodin hydrolysis and the stoichiometry of cefsulodin trapping by the periplasmic beta-lactamase, and (c) comparing the predictions of the trapping and hydrolysis hypotheses with the minimum inhibitory concentrations (MIC) of cefsulodin. The MIC of cefsulodin for strains 3-Pre and 3-Post were 2.35 microM (1.25 micrograms ml-1) and 37.6 microM (20.0 micrograms ml-1) respectively. The permeability parameter for cefsulodin of the outer membrane of the resistant strain was 0.0034 cm3 min-1 mg dry mass-1, so the flux of cefsulodin across its outer membrane at the MIC was calculated to be 0.120 nmol min-1 mg dry mass-1. Hydrolysis of cefsulodin by the beta-lactamase in the periplasm occurred at a rate of 0.118 nmol min-1 mg dry mass-1 which can thus account for resistance by matching the above rate of inflow. Trapping by the beta-lactamase, even with a 1:1 stoichiometry, would require the enzyme to be synthesized at 5.0 micrograms protein min-1 mg dry mass-1 or about 40% of the dry mass/generation. We conclude that hydrolysis, but not trapping, adequately explains the resistance to cefsulodin in P. aeruginosa 3-Post. A similar calculation for latamoxef resistance, using data taken from the literature, led to the same conclusion.

Bacterial Outer Membrane Proteins↗
PubMed1981

Effect of combination of cefsulodin and beta-lactam antibiotics against Serratia marcescens.

The effect of cefsulodin in combination with various beta-lactam antibiotics was examined against Serratia marcescens. In vitro, the optimum ratio for all combinations tested was almost the same (cefsulodin - other antibiotic = 1:1 approximately 1:4). The combinations of cefsulodin-cefazolin and cefsulodin-cefotiam were found to have a synergistic effect and other combinations, such as cefsulodin-cefmenoxime, -ampicillin and -sulbenicillin, an additive effect with the checkerboard dilution and the fixed combination methods. The synergistic effect of cefsulodin-cefotiam was more potent than that of cefsulodin-cefazolin and the effect of both combinations was clearer with heavy than with light inoculum size. With the killing kinetic method, all combinations tested showed a synergistic effect. In vivo, the optimum combination ratios of cefsulodin-cefazolin and cefsulodin-cefotiam were 1:2 and 1:1, respectively, the protective effect of the latter combination being much stronger than that of the former. With the fixed combination method (cefsulodin - other antibiotic = 1:1 approximately 1:4), the effect of the combination of cefsulodin with all antibiotics except cefazolin and cefotiam was additive.

Animals↗
PubMedDate not supplied

Treatment of urinary tract infections due to Pseudomonas aeruginosa with cefsulodin.

Effectiveness of cefsulodin in the treatment of urinary tract infections due to Pseudomonas aeruginosa was evaluated by means of a comparative study with 123 enrolled patients. Seventy-four patients whose therapy could be evaluated were randomly assigned to therapy with either cefsulodin at various dosages or an aminoglycoside (gentamicin, tobramycin, or amikacin). In all cases, the treatment course was five to 10 days (mean, 7.4 days), and levels of cefsulodin in the serum of patients administered the lowest dose (250 mg every 6 hr) exceeded the 90% minimal inhibitory concentration (MIC90) of cefsulodin for P. aeruginosa. Cefsulodin therapy cleared P. aeruginosa from 37 of 50 patients, and therapy with an aminoglycoside cleared P. aeruginosa from 16 of 24 patients. The rate of clearance was unrelated to the antibiotic used (cefsulodin, gentamicin, tobramycin, or amikacin) or to whether patients were catheterized, the infectious agent was resistant to carbenicillin or gentamicin or to 4 micrograms of cefsulodin/ml, or the level of cefsulodin in serum regularly exceeded the minimal bactericidal concentration (MBC) for the infecting strain. The mean MIC and MBC for strains isolated from patients who experienced relapse (failure) were not higher than the mean MIC and MBC for strains cleared by cefsulodin.

Adolescent↗
PubMed1996

Differential susceptibility of aeromonads and coliforms to cefsulodin.

Cefsulodin was evaluated as a potential selective agent for aeromonads. Resistance of Aeromonas and coliform isolates was determined by using a standard disk diffusion technique. A total of 119 Aeromonas and 78 coliform strains were isolated. For 102 of 130 [corrected] Aeromonas isolates (environmental and reference strains), the MIC of cefsulodin was < 8 micrograms/ml. Results of MIC tests by the agar dilution method showed that a concentration of cefsulodin of 10 micrograms/ml or less inhibited the growth of 96% of isolates. In comparison, for 81 of 94 coliform isolates (environmental and reference strains), the MIC of cefsulodin was > 32 micrograms/ml. Because cefsulodin suppresses growth of Aeromonas and other oxidase-positive organisms, total coliform (TC) and Escherichia coli counts on Chromocult Coliform agar (CC agar) without cefsulodin and on CC agar with 10 mg of cefsulodin per liter (CC-CFS) were compared. Variance analysis of data from 14 sewage-polluted irrigation water specimens did not demonstrate any statistically significant difference in the enumeration of E. coli with CC and CC-CFS media. On average, the CC agar recovered 2.46 times as many TCs as CC-CFS. However, Aeromonas colonies made up an average of 58.6% of the TC counts on CC agar. Because no Aeromonas spp. were recovered on CC-CFS, background interference was eliminated and the counts that were obtained reflected more accurately the number of TCs. Results of this study suggest that cefsulodin may be a useful selective agent against Aeromonas spp. which should be included in coliform chromogenic media when high levels of accompanying flora are expected.

Aeromonas↗
PubMed1986

Growth of Yersinia pseudotuberculosis and Yersinia enterocolitica biotype 3B serotype O3 inhibited on cefsulodin-Irgasan-novobiocin agar.

A total of 169 strains of Yersinia spp. were analyzed for their ability to grow on two different kinds of cefsulodin-Irgasan-novobiocin (CIN) agar containing 15 or 4 micrograms of cefsulodin per ml, on salmonella-shigella agar, and on MacConkey agar. CIN media inhibited the growth of Yersinia pseudotuberculosis and Yersinia enterocolitica biotype 3B serotype O3 (3B/O3) but not the growth of the other Yersinia organisms used. Relative to growth on Trypticase soy agar (BBL Microbiology Systems, Cockeysville, Md.) with 6% yeast extract, 48 and 44% of Y. pseudotuberculosis and Y. enterocolitica 3B/O3 strains, respectively, were inhibited on CIN I agar (low cefsulodin concentration), and 83 and 54%, respectively, were inhibited on CIN II agar (high cefsulodin concentration) after incubation for 24 h at 32 degrees C. The inhibition of Y. pseudotuberculosis growth was significantly more extensive on CIN II agar than on CIN I agar. The MICs of cefsulodin and novobiocin clearly indicated a higher susceptibility for Y. pseudotuberculosis than for the other Yersinia organisms at 32 degrees C. All Y. pseudotuberculosis strains were susceptible to cefsulodin at 15 micrograms/ml (the approximate concentration used in CIN II agar). Y. enterocolitica 3B/O3 strains were resistant to cefsulodin, Irgasan, and novobiocin at the concentrations used in CIN media. These findings show that cefsulodin inhibits the growth of Y. pseudotuberculosis at the concentration used in CIN media and that growth inhibition of Y. enterocolitica 3B/O3 is related to a component of the CIN Base.

Agar↗
PubMedDate not supplied

Treatment of skin and soft-tissue infections with cefsulodin.

Skin and soft-tissue infections due to Pseudomonas aeruginosa were treated with intravenous infusions or intramuscular injections of cefsulodin sodium in an open, multicenter study. A total of 40 patients were evaluated to determine the safety and clinical and bacteriologic efficacy of cefsulodin. Cefsulodin was administered alone (31 patients) or in combination with a nonantipseudomonal antibiotic (nine patients) when additional infecting organisms were present. The duration of cefsulodin therapy ranged from two to 46 days (2-12 g/day). Twenty-five patients were treated at New Orleans hospitals for postoperative wound, traumatic wound, and skin ulcer infections with cefsulodin alone or in combination with nonantipseudomonal antibiotic. Therapy with cefsulodin (2-8 g/day) ranged from four to 37 days. P. aeruginosa was eradicated in all the patients, and all clinical responses were considered satisfactory. Fifteen patients were treated at the collaborative centers for postsurgical wound, traumatic wound, skin ulcer, cellulitis, and subcutaneous abscess infections. Therapy with cefsulodin (4-12 g/day) ranged from five to 45 days. The bacteriologic cure rate for assessable patients was 87% (13 of 15 patients), and a satisfactory clinical response was observed in 93% (14 of 15).

Abscess↗
PubMedDate not supplied

Cefsulodin therapy for osteomyelitis due to Pseudomonas aeruginosa.

The results of treating chronic Pseudomonas aeruginosa osteomyelitis with cefsulodin at Rush-Presbyterian-St. Luke's Medical Center (RPSLMC) and eight other institutions are summarized. Eleven patients whose infections were proven by bone-biopsy culture were treated with cefsulodin at RPSLMC; one received two courses of treatment. Efficacy of therapy was evaluated for eight patients, all of whom had a polymicrobial infection. The average age of the patients was 52.3 years (range, 28-85). All had serious underlying illnesses or associated conditions. The mean inhibitory concentration of cefsulodin for the isolates of P. aeruginosa was 3.125 micrograms/ml (range, 0.78-6.25 micrograms/ml). Two patients received concomitant therapy with antibiotics not active against P. aeruginosa. Surgical debridement was performed in six of the eight patients. A favorable response was demonstrated in six of the eight patients. Follow-up for seven patients ranged from one week to 12 months, and in the eighth patient follow-up was 32 months. One patient relapsed twice. Seven possible complications of therapy were observed in five of the 11 patients who received cefsulodin; in three of these patients cefsulodin had to be discontinued. In studies of osteomyelitis conducted at other institutions, 10 of 14 patients for whom therapy could be evaluated had a favorable response to cefsulodin. Cefsulodin is a useful agent for the treatment of chronic osteomyelitis associated with P. aeruginosa.

Adolescent↗
PubMed1990

Resistance of Pseudomonas aeruginosa to cefsulodin: modification of penicillin-binding protein 3 and mapping of its chromosomal gene.

Spontaneous cefsulodin-resistant mutants of Pseudomonas aeruginosa PAO4089 were isolated on agar impregnated with 3 mg/l of cefsulodin. This strain does not produce any chromosomal beta-lactamase. The MICs of cefsulodin for the parent and its mutants were 0.78 and 12.5 mg/l, respectively. Complete cross-resistance between cefsulodin and seven other antipseudomonal beta-lactams was noted in the mutants. The mutant gene, designated as pbpB, was mapped by FP5 plasmid-mediated conjugation and found to be near to cys-59 on the PAO chromosome, the gene order being pur-67, oruI, pbpB and cys-59. There were no detectable differences between the parent and its mutants in their outer membrane protein profiles. Penicillin-binding protein assay, by the competition method, with cefsulodin or carbenicillin showed a significant reduction in affinity of PBP3 for these beta-lactams. This PBP is the primary target for cefsulodin in P. aeruginosa. The genetic mechanism by which the cefsulodin-resistant clinical isolates of P. aeruginosa have emerged is discussed.

Acyltransferases↗
PubMed1979

Bacteriological studies with cefsulodin (CGP 7174/E), the first antipseudomonal cephalosporin.

The new cephalosporin, cefsulodin, has considerable antibacterial activity against Pseudomonas aeruginosa. When 217 strains of Ps. aeruginosa were tested against both azlocillin and cefsulodin, 26.3% were found to have the same minimal inhibitory concentration (MIC); the MIC for azlocillin was lower than that for cefsulodin in 16.6% of strains, but higher in 57.1%. 22 gentamicin-resistant strains were all susceptible to cefsulodin. Biophotometer investigations demonstrate less bactericidal effects for cefsulodin and azlocillin than for carbenicillin and ticarcillin using higher inocula than used in the agar of tube dilution test. Cefsulodin and gentamicin are synergistic against Ps. aeruginosa. Using high pressure liquid chromatography and biological techniques, cefsulodin is found to be moderately stable in solution and in standard solid laboratory media.

Anti-Bacterial Agents↗
PubMed1982

Cefsulodin pharmacokinetics and otitis media.

The pharmacokinetics of cefsulodin in the fluids of the ear and eye as well as in serum were studied after intramuscular administration of 200 and 400 mg/kg to eight groups of six guinea pigs. A retention of cefsulodin in the inner ear-similar to that of the aminoglycoside antibiotics - was observed. As the measured perilymph concentrations of cefsulodin and gentamicin are comparable on a weight for weight basis and as the clinical dosage of cefsulodin is much higher than that of gentamicin, the perilymph concentrations of cefsulodin reached in man are probably much higher than those of gentamicin. The results obtained are compared to those of mezlocillin, azlocillin and fosfomycin, Finally, the importance of the cefsulodin perilymph concentrations in the treatment and prophylaxis of infectious inner ear complications due to the most common pathogens of chronic otitis media as well as in the treatment of certain eye infections is discussed.

Animals↗
PubMed1986

Cefsulodin in treatment of Pseudomonas urinary tract infection in patients with spinal cord injury. Comparison with aminoglycosides.

Male patients with spinal cord injury and urinary tract infection with Pseudomonas aeruginosa were treated with cefsulodin (1.0 or 1.5 Gm) every six hours or an aminoglycoside (amikacin 5 mg/Kg or tobramycin 1 mg/Kg) every eight hours for seven days. The study was discontinued after treating 6 patients with aminoglycosides because of the poor results with these antibiotics. At five to nine days after completing treatment P. aeruginosa was eliminated from the urine of 12 to 15 patients (80%) treated with cefsulodin and 3 of 6 patients (50%) treated with an aminoglycoside. When examined at four to six weeks 5 of 15 (33%) of the cefsulodin group had persistent infection or relapse, while 5 of 6 (83%) infections treated with an aminoglycoside either persisted or relapsed. Cefsulodin was discontinued in 1 patient, known to be allergic to penicillin, because of hypersensitivity resulting in periorbital edema and rash. No other serious side effects were noted with cefsulodin or the aminoglycosides. These results indicate that cefsulodin is an effective antibiotic in the treatment of urinary tract infection with P. aeruginosa in patients with neurogenic bladder resulting from spinal cord injury and confirmed previous observations of a poor response of Pseudomonas urinary tract infection to aminoglycosides in this group of patients.

Adult↗
PubMed2001

On-line microdialysis coupled with microbore liquid chromatography with ultraviolet detection for continuous monitoring of free cefsulodin in rat blood.

A microdialysis method followed by a microbore liquid chromatographic ultraviolet detection procedure has been performed for the assay of unbound cefsulodin in rat blood. A microdialysis probe was inserted into the jugular vein for blood sampling. This method involves an on-line design for submitting dialysate into the liquid chromatographic system. The chromatographic conditions consisted of a mobile phase of methanol-100 mM monosodium phosphoric acid (10:90, v/v, pH 5.0) pumped through a microbore reversed-phase column at a flow-rate of 0.05 ml/min. Detection wavelength was set at 265 nm. Microdialysis probes, being laboratory-made, were screened for acceptable in vivo recovery while chromatographic resolution and detection were validated for response linearity as well as intra- and inter-day variabilities. The method was then applied to pharmacokinetics profiling of cefsulodin in the blood following intravenous administration of cefsulodin (20 mg/kg) in rats. Pharmacokinetics were calculated from the corrected data for dialysate concentrations of cefsulodin versus time. Based on pharmacokinetic calculation, cefsulodin best fitted to a two-exponential disposition. This study provided specific pharmacokinetic information for protein-unbound cefsulodin and demonstrated the applicability of this continuous sampling method for pharmacokinetic study.

Animals↗
PubMedDate not supplied

Cefsulodin therapy for infections due to Pseudomonas aeruginosa in patients with burns.

This multicenter trial compared treatment with either cefsulodin or reference antibiotics (gentamicin, tobramycin, amikacin, or ticarcillin) in 67 patients with Pseudomonas aeruginosa infection and burn injury. Safety of treatment was evaluated for all 67 patients; clinical efficacy, for 29; and bacteriologic efficacy, for 26. The average daily dose and duration of treatment for the 37 cefsulodin-treated patients were 5.6 g and 10.3 days, respectively. The percentage of total body surface burned was greater than or equal to 50% for 40% and greater than or equal to 25% for 85% of the patients. Rates of bacteriologic cure for 30 sites of infection were 64% (7/11) for skin and skin-structure infections treated with cefsulodin or reference antibiotics; 100% (1/1) for respiratory tract infections treated with cefsulodin and 33% (2/6) for those treated with reference antibiotics; and 100% (1/1) for septicemia treated with a reference antibiotic. Overall bacteriologic and clinical efficacy for cefsulodin treatment was 67% (8/12) and 73% (11/15), respectively, and for treatment with a reference antibiotic was 56% (10/18) and 64% (9/14), respectively. Cefsulodin was found to be safe and comparable in efficacy to reference antibiotics in this patient population.

Adolescent↗
PubMed1984

Synergistic activity of cefsulodin combined with cefoxitin and sulbactam against Bacteroides species.

The in-vitro activity of cefsulodin combined with sulbactam, cefoxitin or cefotaxime was investigated against 32 strains of beta-lactamase-producing Bacteroides species. Synergy of cefsulodin-sulbactam or cefsulodin-cefoxitin could be demonstrated against 30 of 32 and 32 of 32 strains tested at the concentrations readily achievable in serum. In the presence of 1 mg/l of sulbactam or cefoxitin, more than 90% of the Bacteroides isolated were inhibited by 32 mg/l of cefsulodin. The inhibitory activity of cefsulodin-sulbactam or cefsulodin-cefoxitin combinations was bactericidal against Bact. fragilis and Bact. vulgatus. In contrast, no synergistic inhibitory or bactericidal activities can be observed by the cefsoludin-cefotaxime combination. Both sulbactam and cefoxitin were potent inhibitors of beta-lactamases produced by Bact. fragilis and Bact. melaninogenicus suggesting that this inhibitory activity might be one of the factors contributing to the synergistic combinations.

Bacteroides↗
PubMed1985

Growth of Aeromonas spp. on cefsulodin-Irgasan-novobiocin agar selective for Yersinia enterocolitica.

Twenty-eight strains of Aeromonas spp. were analyzed for their ability to grow on two different kinds of cefsulodin-Irgasan (triclosan; Ciba-Geigy AG, Basel, Switzerland)-novobiocin (CIN) agar containing 15 or 4 mg of cefsulodin per ml and on inositol-bile salts-brilliant green (IBB) agar. Relative to blood agar, 68% of the strains were inhibited by more than 2 logs (i.e., less than 1% growth) at 37 degrees C (39% at 25 degrees C) on CIN I (high cefsulodin concentration), 7% were inhibited at either temperature on CIN II (low cefsulodin concentration), 4% were inhibited on IBB agar at 37 degrees C, and none were inhibited on IBB agar at 25 degrees C. These results reflect the MICs of cefsulodin on CIN Base: the MIC for 50% of the strains was 8 mg/liter at 37 and 25 degrees C, and the MICs for 90% of the strains were 16 mg/liter at 37 degrees C and 64 mg/liter at 25 degrees C. The MICs of Irgasan and novobiocin were far beyond the concentrations used in CIN media. We argue that CIN agar containing 4 mg of cefsulodin per ml (CIN II) can be used for the simultaneous detection of Aeromonas spp. and Yersinia spp.

Aeromonas↗
PubMed1988

Transperitoneal movement and pharmacokinetics of cefotiam and cefsulodin in patients on continuous ambulatory peritoneal dialysis.

The kinetics of cefotiam and cefsulodin were studied in plasma and dialysate after intravenous and intraperitoneal administration of 1 g to patients undergoing continuous ambulatory peritoneal dialysis. Instillation of autologous hemoglobin as a marker permitted calculation of the cavity volume and, hence, the rate of transfer to and from the peritoneal cavity with time. The patients were divided into 4 groups. Groups 1 and 2 were intravenously given cefotiam (5 patients) and cefsulodin (4 patients), respectively. Groups 3 and 4 (5 patients each) were given cefsulodin intraperitoneally. Group 3 did not have peritonitis, while the patients in Group 4 were studied during peritonitis. Blood and dialysate samples were obtained at selected times during the 5-hour dwell and, for plasma, until 24 hours after drug administration. Pharmacokinetic analysis of the data showed that only 6.0 and 8.7% of the intravenous doses of cefotiam and cefsulodin, respectively, were recovered in the dialysate at the end of the dwell. The net amounts of cefsulodin lost from the dialysate after intraperitoneal administration were 81 and 84%, in Groups 3 and 4 respectively. The peritoneal transfer clearances (using a unidirectional clearance model), calculated after intravenous (17 +/- 10 ml/min, Group 2) and intraperitoneal (17 +/- 5 ml/min, Group 3) administrations were the same. Mass balance of cefsulodin in the body and in the dialysate after intraperitoneal administration indicated that a significant amount (40%, Group 3) of the dose is unaccounted for. One explanation for this imbalance is retention of the drug in the peritoneal lining. This hypothesis is supported by the retention being lower in the peritonitis patients (less than 20%, Group 4), for whom the linings are expected to be partially eroded.

Adult↗
PubMed1996

Combination therapy of Pseudomonas aeruginosa pyelonephritis in neutropenic mice with human antilipopolysaccharide monoclonal antibody and cefsulodin.

PURPOSE: These studies were designed to determine the combined inhibitory effect of a human monoclonal antibody (MAb) and cefsulodin on Pseudomonas aeruginosa renal infection in a neutropenic condition. MATERIALS AND METHODS: Protection against the infection of mice was estimated by survival rate and bacterial numbers in the kidney and blood. Opsonophagocytic assay by human polymorphonuclear neutrophils (PMNs) and fluorescence activated cell sorter (FACS) analysis were also examined. RESULTS: Treatment of infected mice with MAb combined with a suboptimal dose of cefsulodin prevented the mice from developing pyelonephritis and bacteremia and resulted in a significantly higher survival rate than treatment with either MAb or cefsulodin alone (p < 0.01). When bacteria were preexposed to cefsulodin, a significant enhancement in opsonophagocytic killing with MAb was observed. Fluorescence activated cell sorter analysis suggested that the bacteria incubated with 1/4 minimal inhibitory concentration (MIC) of cefsulodin showed greater binding of MAb to bacteria than the control. CONCLUSION: The combination therapy with human antilipopolysaccharide MAb and cefsulodin is useful for P. aeruginosa pyelonephritis in neutropenic hosts.

Animals↗