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PubMed1999

Increasing prevalence of antimicrobial resistance among uropathogens causing acute uncomplicated cystitis in women.

CONTEXT: Guidelines for the management of acute uncomplicated cystitis in women that recommend empirical therapy in properly selected patients rely on the predictability of the agents causing cystitis and knowledge of their antimicrobial susceptibility patterns. OBJECTIVE: To assess the prevalence of and trends in antimicrobial resistance among uropathogens causing well-defined episodes of acute uncomplicated cystitis in a large population of women. DESIGN: Cross-sectional survey of antimicrobial susceptibilities of urine isolates collected during a 5-year period (January, May, and September 1992-1996). SETTING: Health maintenance organization. PATIENTS: Women aged 18 to 50 years with an outpatient diagnosis of acute cystitis. MAIN OUTCOME MEASURES: Proportion of uropathogens demonstrating in vitro resistance to selected antimicrobials; trends in resistance over the 5-year study period. RESULTS: Escherichia coli and Staphylococcus saprophyticus were the most common uropathogens, accounting for 90% of the 4342 urine isolates studied. The prevalence of resistance among E coli and all isolates combined was more than 20% for ampicillin, cephalothin, and sulfamethoxazole in each year studied. The prevalence of resistance to trimethoprim and trimethoprim-sulfamethoxazole rose from more than 9% in 1992 to more than 18% in 1996 among E coli, and from 8% to 16% among all isolates combined. There was a statistically significant increasing linear trend in the prevalence of resistance from 1992 to 1996 among E coli and all isolates combined to ampicillin (P<.002), and to cephalothin, trimethoprim, and trimethoprim-sulfamethoxazole (P<.001). In contrast, the prevalence of resistance to nitrofurantoin, gentamicin, and ciprofloxacin hydrochloride was 0% to 2% among E coli and less than 10% among all isolates combined, and did not change significantly during the 5-year period. CONCLUSIONS: While the prevalence of resistance to trimethoprim-sulfamethoxazole, ampicillin, and cephalothin increased significantly among uropathogens causing acute cystitis, resistance to nitrofurantoin and ciprofloxacin remained infrequent. These in vitro susceptibility patterns should be considered along with other factors, such as efficacy, cost, and cost-effectiveness in selecting empirical therapy for acute uncomplicated cystitis in women.

Acute Disease↗
PubMed1997

Antibiotic diffusion pathways in the outer membrane of Pseudomonas aeruginosa.

We investigated the effect of a temperature shift from 37 degrees C to 17 degrees C on the steady-state diffusion rate of imipenem and cephalothin by evaluating periplasmic drug concentrations in intact cells of Pseudomonas aeruginosa, which overexpresses the extended spectrum beta-lactamase. We found that the ratio of periplasmic imipenem concentration at 17 degrees C relative to that of 37 degrees C was 1.03+/-0.1, whereas that of cephalothin was 0.43+/- 0.09. Accumulation rates of cell-associated tetracycline and fluoroquinolone at 17 degrees C were roughly 1/16 and 1/8, respectively, compared with that at 37 degrees C. We concluded from these data that cephalothin and possibly most other antibiotics excepting carbapenems cross the outer membrane of P. aeruginosa mainly by dissolving in the lipid phase but probably not passing through the porin channel. This may explain why the outer membrane of P. aeruginosa is a tight barrier against the penetration of antibiotics.

Anti-Bacterial Agents↗
PubMedDate not supplied

Nephrotoxicity of cefotiam in rats.

Eight-week-old Wistar female rats were treated intramuscularly with 300, 1,000 and 3,000 mg/kg/day of cefotiam for five days. The nephrotoxicity of cefotiam was determined on the basis of the number of tubular epithelial cells excreted, the malate dehydrogenase activity in the urine and the histological examination of the kidneys. Cephalothin (3,000 mg/kg/day) was used as a reference compound. There were slight increases in the number of tubular epithelial cells excreted and in the malate dehydrogenase activity in the urine of some animals receiving 3,000 mg/kg/day of cefotiam or cephalothin. All of these changes disappeared within a few days after the dosing period. The histological examination of the kidneys at the end of both the dosing (5 days) and the recovery (7 days) periods revealed no pathological changes indicating nephrotoxicity. It was concluded that the nephrotoxicity of cefotiam was comparable to that of cephalothin; the urinary changes in animals receiving the highest dose were considered to be an early sign of nephrotoxicity. The maximum non-toxic dose of cefotiam was 1,000 mg/kg/day under the present experimental conditions.

Animals↗
PubMed1984

Activity of cephalosporins against methicillin-resistant coagulase-negative staphylococci.

Using a dilution method (37 degrees C, 42 h), six of ten methicillin-resistant strains of coagulase-negative staphylococci were found to be resistant to cephalothin. Of 20 variations in the method for detection of resistance to methicillin and cephalothin, broth dilution tests at 30 degrees C for 42 h were the most sensitive. Differences are explained by low percentages of cephalothin-resistant clones in methicillin-resistant strains.

Cephalosporins↗
PubMedDate not supplied

In-vitro activity of piperacillin/tazobactam relative to other antibiotics against blood culture isolates.

Resistance of bacteria to antibiotics is an increasing problem in many countries. Accurate locally relevant information is essential for detection and control of emerging resistance and to facilitate choice of empirical antibiotic therapy in the immediate management of seriously ill patients. We have determined the minimum inhibitory concentration of piperacillin/tazobactam for 97 strains of bacteria (55 Enterobacteriaceae, 13 non-fermentative Gram-negative bacilli, 22 Staphylococcus aureus, 6 Enterococcus faecalis and 1 Bacillus cereus) isolated from blood cultures and compared its activity to that of amoxycillin, co-amoxiclav, cephalothin, cefotaxime, ceftazidime, ciprofloxacin, gentamicin, piperacillin, cefotaxime. The strains were consecutive non-fastidious isolates with the following qualifications: coagulase negative staphylococci and diphtheroids were excluded and the number of Staphylococcus aureus isolates was limited to 12 methicillin-resistant and 10 methicillin-sensitive strains. Multiple isolates of the same species from individual patients were not included. The minimum inhibition concentrations of methicillin, penicillin, teichoplanin and vancomycin were also determined for specific groups of organisms. MICs were determined by the Etest method (AB Biodisk, Solna, Sweden) on Mueller Hinton agar. The MICs of appropriate American Type Culture Collection control strains were determined. Based on the interpretative criteria of the National Committee for Clinical Laboratory Standards (USA), 87 per cent of Gram-negative bacilli were susceptible to piperacillin/tazobactam compared with amoxycillin 26 per cent, cephalothin 35 per cent, co-amoxiclav 54 per cent, piperacillin 56 per cent, cefotaxime 69 per cent, ceftazidime 84 per cent, gentamicin 85 per cent and ciprofloxacin 91 per cent. Of all isolates 75 per cent were sensitive to piperacillin/tazobactam, compared with amoxycillin 22 per cent, cephalothin 35 per cent, piperacillin 41 per cent, co-amoxiclav 52 per cent, cefotaxime 59 per cent, ceftazidime 60 per cent, gentamicin 74 per cent and ciprofloxacin 77 per cent. Two isolates (1 E. coli and 1 Klebsiella pneumoniae) with antibiograms consistent with the relatively new resistance phenomenon of extended spectrum beta-lactamase production were identified. The spectrum of activity of piperacillin-tazobactam for empirical antibiotic therapy is significantly greater than that of piperacillin alone and is similar to that of ciprofloxacin and gentamicin.

Anti-Bacterial Agents↗
PubMed1982

Primary culture of adipoblasts from obese and lean Zucker rat adipose tissue.

Adipocyte precursors derived from the epididymal fat pads of young adult lean (FaFa) and obese (fafa) Zucker rats were established in primary culture. The two types of culture were used to assess intrinsic cellular differences in proliferative capacity, lipoprotein lipase (LPL) activity and triglyceride (TG) accumulation related to genotype. Proliferative capacity was similar over seven days in vitro in lean- and obese-derived cultures. Heparin-releasable LPL activity was significantly greater in lean- than in obese-derived cultures grown in media supplemented with penicillin and streptomycin (pen-strep). However, when grown in media supplemented with cephalothin, heparin-releasable and total LPL activity increased significantly in obese-derived cultures and equalled LPL activity in lean-derived cultures. Substantial LPL activity was measurable in both types of culture at confluence, before exposure to media that promoted lipid-filling. TG accumulation was significantly greater in lean-than in obese-derived cultures in the presence of pen-strep but was similar in both culture types grown in cephalothin. These data support our hypothesis that the fa gene may affect mechanisms of protein turnover regulation, since pen-strep, but not cephalothin, has inhibitory effects on mammalian protein synthesis and degradation. The substantial LPL activity present in confluent, but unconverted cultures, suggests that some percentage of cells in the confluent monolayers are adipoblasts.

Adipose Tissue↗
PubMed2004

Incorporation of different antibiotics into carbonated hydroxyapatite coatings on titanium implants, release and antibiotic efficacy.

Carbonated hydroxyapatite (CHA) coatings were applied onto titanium implants by using a biomimetic precipitation method. Different antibiotics were incorporated into the CHA coatings and their release and efficacy against bacteria growth were studied in vitro. The following antibiotics were used within this study: cephalothin, carbenicillin, amoxicillin, cefamandol, tobramycin, gentamicin and vancomycin. Increased concentrations of antibiotics in the coating solution led to a higher quantity of antibiotic incorporated into the CHA coating. Some antibiotics were better incorporated than others depending on their chemical structure. Antibiotics, containing carboxylic groups such as cephalothin, carbenicillin and cefamandol, were better incorporated than antibiotics lacking these groups. A bacterial inhibition test on Staphylococcus aureus bacteria showed inhibition of growth for all antibiotics that were released from the CHA coating. A release test was conducted in phosphate buffer saline PBS at pH 7.4 and 37 degrees C and showed that antibiotics containing carboxylic groups like cephalothin were slower released from the CHA coating than others. These results suggest that certain antibiotics are able to bind/chelate with calcium, resulting in a better incorporation into the CHA coating and a slower release. Antibiotics incorporated in CHA coatings on titanium implants might be used to prevent post-surgical infections and to promote bone-bonding of orthopedic devices.

Anti-Bacterial Agents↗
PubMed2004

Shifting trends in in vitro antibiotic susceptibilities for common ocular isolates during a period of 15 years.

PURPOSE: To assess the in vitro susceptibility of the most common ocular bacterial isolates to several antibiotics and verify changing trends in the antibiotic susceptibility in a 15-year period. DESIGN: Experimental study. METHODS: All cultures positive for Staphylococcus aureus, coagulase-negative Staphylococcus (CNS), Streptococcus sp, and Pseudomonas sp in conjunctival (n = 4,585) and corneal (n = 3,779) samples from patients seen at the Federal University of São Paulo from 1985 to 2000 were evaluated. Cultures were performed in liquid and solid media, and susceptibility tests were done to amikacin, gentamicin, neomycin, tobramycin, ciprofloxacin, norfloxacin, ofloxacin, cephalothin, and chloramphenicol. RESULTS: Amikacin and neomycin showed an improvement of their sensitivity during the study period (88%-95% and 50%-85%, respectively) for corneal and conjunctival samples. Gentamicin and tobramycin revealed a decrease of sensitivity in time, from 95% to less than 80% in corneal and conjunctival samples. Ciprofloxacin, norfloxacin, and ofloxacin had good sensitivity to all evaluated bacteria, better in conjunctiva (95%) than in cornea (90%). Sensitivity of S. aureus to cephalothin decreased during the study but was still 98% for CNS. Chloramphenicol had good sensitivity to S. aureus (85% in corneal and 92%in conjunctival samples), CNS (87% and 88.5%), and Streptococcus sp (95% and 96%). CONCLUSIONS: Gentamicin, tobramycin, and cephalothin decreased their in vitro susceptibility to all tested pathogens. The fluoroquinolones remained a good choice in the treatment of ocular infections, with high suscep-tibility to all pathogens tested. Chloramphenicol also revealed an increase in its susceptibility to all bacteria evaluated.

Anti-Bacterial Agents↗
PubMed2003

Isolation of antimicrobial-resistant Escherichia coli from retail meats purchased in Greater Washington, DC, USA.

Four hundred and seventy-two generic Escherichia coli isolates were recovered from ground and whole retail beef, chicken, pork, and turkey obtained from Greater Washington, DC, USA during the years 1998 to 2000. Many of the isolates displayed resistance to tetracycline (59%), sulfamethoxazole (45%), streptomycin (44%), cephalothin (38%) and ampicillin (35%). Resistance was also observed, but to a lesser extent, to gentamicin (12%), nalidixic acid (8%), chloramphenicol (6%), ceftiofur (4%) and ceftriaxone (1%). Sixteen percent of the isolates displayed resistance to one antimicrobial, followed by 23% to two, 23% to three, 12% to four, 7% to five, 3% to six, 2% to seven and 2% to eight. Three E. coli isolates were shown to possess Shiga toxin genes (stx2) via PCR; all were O non-typeable and were recovered from ground beef samples purchased on the same day at the same supermarket. One of the Shiga toxin-producing E. coli (STEC) isolates was susceptible to each of the antimicrobials tested, whereas one displayed resistance to cephalothin and sulfamethoxazole, and one displayed resistance to ampicillin, cephalothin, gentamicin, streptomycin, sulfamethoxazole and tetracycline. Findings from this study indicate that retail raw meats may often be contaminated with antimicrobial-resistant E. coli.

Animals↗
PubMed2004

Detection of extended-spectrum beta-lactamase-producing, multidrug-resistant environmental isolates of Escherichia coli that bind to human bladder cells.

Compared to the number of studies examining extended-spectrum beta-lactamase (ESBL)-producing clinical isolates, environmental ESBL-producers have not been studied extensively. To investigate environmental ESBL-producing Escherichia coli, 22 cephalothin-resistant E. coli were isolated from Han River in Seoul, Korea. These isolates were resistant to ampicillin, cephalothin, and gentamicin, and 14 isolates among these were resistant to norfloxacin. All of these isolates produce AmpC and CMY, OXA, or TEM as determined by isoelectric point focusing (IEF) gel electrophoresis and PCR. One isolate (57-214) producing AmpC and OXA was resistant to all antibiotics (ampicillin, cephalothin, norfloxacin, gentamicin, cefotaxime, ceftazidime) tested in this study. Six isolates, including isolate 57-214, could adhere to T24 human bladder cells, and these isolates were not related to each other as shown with random amplified polymorphic DNA (RAPD). Results showed that environmental ESBL-producing E. coli is able to colonize in bladder cells and directly cause antibiotic-resistant urinary tract infection.

Bacterial Adhesion↗
PubMed1977

Therapy for experimental intraabdominal sepsis: comparison of four cephalosporins with clindamycin plus gentamicin.

An experimental model of intraabdominal sepsis in rats was used for evaluation of treatment with four cephalosporins: cephalothin, cefazolin, cefoxitin, and cefamandole. Doses were 115 mg of each of the cephalosporins/kg and, in additional experiments, 350 mg of cephalothin or cefazolin/kg. Response to treatment was evaluated by mortality rate and the incidence of intraabdominal abscess. All four cephalosporins and gentamicin produced a similar reduction in mortality rates. There was a marked variation in incidence of abscess dependent upon the cephalosporin selected and the dosage tested. Regimens most effective in reducing abscesses were clindamycin, low-dose cefoxitin, or high-dose cephalothin.

Abdomen↗
PubMed1972

Biological properties of three 3-heterocyclic-thiomethyl cephalosporin antibiotics.

Three new cephalosporin antibiotics, prepared by substitution of heterocyclic groups on 7-aminocephalosporanic acid, possess certain desirable chemical or biological properties. All three compounds are active in vitro against a variety of gram-positive and gram-negative bacteria. Minimal inhibitory concentrations (MIC) of these bactericidal antibiotics were not significantly affected by changes in pH or NaCl content of nutrient broth, or by the use of different inoculum sizes. However, agar-dilution MIC values were generally two- to fourfold lower than the MIC values in comparable broth-dilution tests. Stability to cephalosporinase by two of the compounds extended their antibacterial spectra over cephalothin and cephaloridine to include strains of Enterobacter sp. and indole-positive Proteus sp. Binding to serum proteins of the new cephalosporins was intermediate between cephalothin and cephaloridine. Excellent concentrations of the antibiotics were attained in mouse blood, after subcutaneous administration of 20 mg per kg. In vitro biological characteristics of the antibiotics were verified by successful therapy of experimental mouse infections. Regression lines were calculated to show the correlation of agar-dilution MIC values with zones of inhibition by the disc testing procedure. Because each of the three new cephalosporins has certain advantageous properties over cephalothin and cephaloridine, additional toxicological and pharmacological data should be obtained for all three compounds.

Amidohydrolases↗
PubMed1976

In vitro and in vivo evaluation of ceftezole, a new cephalosporin derivative.

Ceftezole, a new cephalosporin derivative, was compared with cefazolin, cephaloridine, and cephalothin. Data obtained indicate that it is a broad-spectrum antibiotic, with almost identical antimicrobial activity against pathogenic organisms isolated from patients. The therapeutic effect of ceftezole on experimental infections in mice was similar to that of cefazolin and was superior to that of cephalothin. The binding of ceftezole to serum proteins was somewhat less than that of cefazolin. The concentrations of ceftezole in the sera of test animals and human volunteers were determined after intramuscular injection of 20 mg/kg and after a single dose of 500 mg, respectively. The concentration of ceftezole in the serum of volunteers peaked at 24.9 mug/ml 15 min after injection and remained effective (about 2.6 mug/ml) at 4 h. The half-life in serum under the same conditions was 56 min, i.e., about one-half that of cefazolin. The 24-h urinary recovery rate was 87.5%. Most of the administered ceftezole was excreted unchanged mainly through the urinary tract. The biliary excretion rate in SD strain rats after intramuscular injection of 20 mg/kg was about 4.4%. As compared with commercially available cephalosporins, ceftezole was second only to cefazolin in biliary excretion rate. Various tissue levels of ceftezole in animals were higher than cephalothin but, with the exception of renal levels in the early stage after administration, were lower than cefazolin.

Adult↗
PubMed1977

Stability of cephalosporins in horse serum.

The antibiotic activity of cephalothin, cephaloridine, cephalexin, cephaloglycin, cefazolin, and cefamandole was determined after storage for up to 30 days in horse serum at -10 and 4 degrees C. Cephalothin, cefamandole, cefazolin, and cephalexin were stable for at least 30 days at -10 degrees C, whereas cephaloridine lost 29% of its initial activity and cephaloglycin lost more than 50%. Cefamandole, cefazolin, and cephalexin could only be stored for 3 days at 4 degrees C without significant loss in activity, whereas cephalothin, cephaloridine, and cephaloglycin could be stored for only 1 day. Repeated freezing and thawing had a detrimental effect on the stability of cephaloridine.

Animals↗
PubMed1977

Laboratory evaluation of FR10024 a new cephalosporin derivative.

FR10024 is a broad-spectrum antibiotic. The in vitro antibacterial activity of FR10024 against clinical isolates of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis is greater than that of any of the cephalosporins developed to date. Indole-positive Proteus, Enterobacter, and Citrobacter are resistant to FR10024, as is true for the other cephalosporins. However, more than half of the strains of Enterobacter and Citrobacter tested were susceptible to FR10024 at an inoculum of 10(6) cells/ml. A single subcutaneous injection of FR10024 to mice with peritoneal infections due to S. aureus and several species of gram-negative bacilli gave a protective effect inferior to that of cefazolin but appeared to be superior to that of cephalothin. When given in two divided doses, however, the protective effect of FR10024 was enhanced and almost equaled that of cefazolin. The serum levels and rates of urinary recovery of FR10024 varied in different animal species. The mean peak serum level of FR10024 in humans after a single intramuscular injection of 500 mg was two times higher than that of cephalothin. The serum half-life after intramuscular injections of 250 and 500 mg was slightly shorter than that of cephalothin. After receiving 250 mg of FR10024 intramuscularly the urinary recovery rate was 87.7% in healthy volunteers. The biliary excretion rate of FR10024 was particularly high. The 24-h excretion of FR10024 in rats was 63.3%, this being six to seven times higher than that for cefazolin, which has the highest biliary excretion of the other known cephalosporins. When FR10024 was injected intramuscularly (20 mg/kg), it was found that the hepatic levels of FR10024 in rats were the highest of all the cephalosporins, including cefazolin, but the levels of FR10024 in other tissues were not as high as those of cefazolin.

Adult↗
PubMed1977

Comparative susceptibility of anaerobic bacteria to ticarcillin, cefoxitin, metronidazole, and related antimicrobial agents.

The in vitro antimicrobial activity of two newer agents, ticarcillin and cefoxitin, against 204 recent clinical isolates of anaerobic bacteria was determined by an agar dilution technique, and compared to their related compounds carbenicillin, cephalothin, and penicillin, as well as metronidazole, clindamycin, and chloramphenicol. Ticarcillin was similar to carbenicillin, and cefoxitin was more active than cephalothin. At readily achievable blood concentrations of each antimicrobial agent, ticarcillin was slightly less active than clindamycin against Bacteroides fragilis. Cefoxitin was superior to cephalothin and penicillin against B. fragilis. Penicillin remained highly active against all obligate anaerobes other than B. fragilis. Metronidazole, while highly effective against B. fragilis and Clostridium perfringens, was only intermediately effective against anaerobic gram-positive cocci and relatively inactive against nonsporulating anaerobic gram-positive bacilli. Further evaluation of the clinical efficacy of ticarcillin, carbenicillin, and cefoxitin against anaerobic infections is indicated.

Anaerobiosis↗
PubMed1978

Diffusion disk susceptibility testing with cefaclor.

The reliability of the standardized 30-mug cephalothin disk and that of an experimental 30-mug cefaclor disk in predicting probable clinical susceptibility to cefaclor were compared. Quantitative determinations of cefaclor susceptibility were measured by the World Health Organization International Collaborative Study agar dilution procedure; diffusion disk tests were performed by the standardized U.S. Food and Drug Administration disk test. The cephalothin disk erred in predicting probable susceptibility in 52% of isolates of Enterococcus spp. resistant to 16 mug or less of cefaclor per ml; the cefaclor disk did not. The cephalothin disk erred in correctly predicting susceptibility in only 20% of cefaclor-susceptible isolates of Enterobacter spp.; the cefaclor disk correctly predicted susceptibility for 70%. These results indicate the need for further evaluation of a separate cefaclor disk for use in susceptibility testing with this new cephalosporin.

Cephalosporins↗
PubMed1979

Cefatrizine activity compared with that of other cephalosporins.

Cefatrizine, a new orally administered cephalosporin, was tested against 400 clinical isolates. Cefatrizine had excellent activity against gram-positive cocci, inhibiting all except enterococci at minimal inhibitory concentrations below 1 mug/ml. Cefatrizine inhibited the majority of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Salmonella at concentrations below 12.5 mug/ml. Although cefatrizine was not hydrolyzed by many beta-lactamases, it did not inhibit a number of strains of Enterobacter, Serratia, or indole-positive Proteus. Cefatrizine was more active than cephalothin or cephalexin against E. coli, Klebsiella, Enterobacter, Citrobacter, Salmonella, and Shigella. Its overall activity was less than that of cefoxitin against strains resistant to cephalothin, but its activity against cephalothin-susceptible strains was equivalent to that of cefamandole.

Bacteria↗