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PubMed1977

Possible beta-lactamase activities detectable in infective clinical specimens.

Biological beta-lactam antibiotic-inactivating activities were detected in bacteriuria and suppurating pleural fluids. Clinical specimens were sterilized with membrane filters and the amounts of ampicillin and/or cephalothin which were being inactivated by 1 ml of each filtrate were determined. In general, filtrates which originally yielded Klebsiella sp. tended to show activity against ampicillin; whereas those yielding Enterobacter sp. and Pseudomonas aeruginosa showed activity against cephalothin.

Amidohydrolases↗

PubMed1977

Cephalosporins. II. 7-(O-Aminomethyl-phnylacetamido) cephalosporanic acids with six membered heterocycles in the C-3 side chain.

7-(o-Aminomethylphenylacetamido)cephalosporanic acids with six-membered heterocycles in the C-3 side chain were prepared by nucleophillic substitution of 7-ACA at the C-3 acetoxy group followed by N-acylation of the 7-amino group. The 7-side chain acid, o-aminomethylphenylacetic acid (5), was prepared by two new convenient routes, which involved Schmidt reaction of indanone (2) followed by cleavage of the lactam ring or reduction of o-cyanophenylacetic acid (10) starting from o-nitrotoluene. The antibacterial activity of the cephalosporins in this series depends on the heterocycle in the C-3 side chain. In general pyridazines gave cephalosporin derivatives possessing better activity than those with a pyridine or pyrimidine ring. The most active member of the new cephalosporins was 7-(o-aminomethylphenylacetamido)-3-(6-hydroxypyridazin-3-ylthilmethyl)-3-cephem-4-carboxylic acid (BB-S 150) (1g) which has in vitro antibacterial activity superior to cephalothin and cefazolin against both gram-negative and gram-positive organisms. The in vitro activity of BB-S 150 determined in mice was superior to cephalothin and comparable to cefazolin.

Animals↗

PubMed1991

Synthesis and antibacterial activity of new C-10 quinolonyl-cephem esters.

A series of cephalosporins derived from cephalothin containing an ester-linked quinolonyl substituent at the C-10 position (C-10 quinolonyl-cephem esters) has been prepared and evaluated for in vitro antibacterial activity. The C-10 quinolonyl-cephem esters exhibited a broadened spectrum of activity when compared with cephalothin and the corresponding quinolones, including activity against beta-lactamase-producing bacteria.

Bacteria↗

PubMed1975

Effects of drugs and parenteral solutions on vascular fibrinolytic activity.

The effects of saline, D5W, D10W, dextran, penicillin, cephalothin, and the Renografin "dyes" on vascular fibrinolytic activity were evaluated in in vitro experiments and in caninne preparations. Saline, D5W, D10W, and dextran did not affect fibrinolytic activity. High concentrations of the Renografin "dyes" and penicillin decreased fibrinolytic activity in vitro. Cephalothin, with an increased association of postinfusion in vitro studies but demonstrated minimal effect during the in vivo studies during which sufficiently high local concentrations of drug may not have been obtained. It is concluded that, although intimal damage, stasis, and/or hypercoagulability are responsible for the development of post infusion thromboses, local hypofibrinolytic activity is induced by some infusions and might contribute to the persistence and propagation of the thromboses.

Angiography↗

PubMed1976

The in vitro spectrum of the cephalosporins.

The cephalosporins may currently be classified according to their relative susceptibility to beta-lactamases. Cefoxitin, cefamandole, cefatrizine, and cephanone are relatively resistant to the gram-negative beta-lactamases, whereas cephalothin, cefamandole, and cefoxitin are resistant to staphylococcal beta-lactamase. Although the inhibitory activity of cephalothin is representative of that of cephaloridine, cephalexin, cefazolin, cephapirin, cephacetrile, and cephradine, there are significant differences between its activity and that of cefoxitin, cefamandole, and cefatrizine, especially against Enterobacter, Serratia, indole-positive Proteeae, Bacteroides fragilis, and ampicillin-resistant Haemophilus influenzae.

Bacteria↗

PubMed1990

The use of sensitivity discs in the identification of Campylobacter species.

Filter paper discs were impregnated with a solution containing 20 mg of triphenyltetrazolium chloride per millilitre, and used in the typing of catalase-positive Campylobacter species. Also used were filter paper discs impregnated with cephalothin at 30 micrograms/ml, 60 micrograms/ml and 3 mg/ml and nalidixic acid at the same concentrations, as well as commercially available discs containing 30 micrograms of, respectively, cephalothin and nalidixic acid. Results obtained proved the technique to be reliable and easier to interpret than previously used methods, and laboratory prepared filter paper discs compared favourably with commercial discs.

Animals↗

PubMed1986

Neonatal septicemia caused by coagulase-negative staphylococci.

We report our experience with coagulase-negative staphylococcal infection over a period of 1 year. The incidence of coagulase-negative staphylococcus septicemia was 4.25% (13 newborn infants) of the 306 admissions to our Neonatal Intensive Care Unit. Ten patients (76.9%) were premature infants. Four infants in our series were less than 48 h of age. Two of these were presumably born with the infection. Six infants had involvement of the lungs. The strains of coagulase-negative staphylococci cultured from all cases of neonatal septicemia were sensitive to cephalothin, but were considerably less sensitive to the currently used antibiotic combinations. Our observations indicate that coagulase-negative staphylococci must be suspected in early or late neonatal sepsis, and that early antibiotic treatment by cephalothin may prevent morbidity.

Blood Transfusion, Intrauterine↗

PubMed1978

Combination antibiotic therapy in an outbreak of prosthetic endocarditis caused by Staphylococcus epidermidis.

The efficacy of combination antibiotics in vivo and in vitro was studied during an outbreak of prosthetic endocarditis caused by Staphylococcus epidermidis in 10 patients. The epidemic curve suggested that patients were infected at the time of their operation, with an interval from that time until diagnosis of 11 days to 20 months. The overall mortality was 50%. Four of six patients treated with gentamicin in combination with a penicillin analogue, a cephalosporin or clindamycin survived without reoperation. One of four patients survived when treated with regimens that did not include gentamicin. In vitro studies showed a median minimum inhibitory concentration for methicillin of 8.0 microgram/mL, compared with 0.1 microgram/mL for cephalothin, clindamycin and gentamicin, and a synergistic bactericidal effect between gentamicin and methicillin, cephalothin or clindamycin. These data suggest that gentamicin is a valuable component of combination antibiotic therapy in prosthetic endocarditis caused by S. epidermidis.

Adult↗

PubMed1979

The value of prophylactic antibiotics in aorat-coronary bypass operations: a double-blind randomized trial.

Prospective and retrospective studies were performed to determine the efficacy of prophylactic antibiotics in preventing infections in patients undergoing arota-coronary bypass. One-hundred five patients were randomized in a double-blind fashion to receive either methicillin or saline-placebo for 3 days. The over-all infection rate was 26.7% with 48.9% in the control group and 8.6% in the methicillin group (p less than 0.001). Significant sternal wound infection developed in 21.3% of the control group and 0% of the methicillin group (p less than 0.01). Staphylococcus aureus was the predominant organism causing significant sternal infection (methicillin group versus control group, 5.2% and 21.3%; p less than 0.05). The length of postoperative stay in hospital and the number of days with fever was significantly greater in the control group than in the methicillin group (p less than 0.001). During the same period of time, 160 patients were studied retrospectively. Of these, 150 patients received cephalothin prophylaxis and 10 received methicillin. Comparison of the rates of infection in the cephalothin group to the total methicillin group (prospective and retrospective) showed no significant difference. The study clearly demonstrated that a short course of prophylactic antistaphlococcal penicillin or cephalosporin is justified in aorta-coronary bypass.

Cephalothin↗

PubMed1985

Comparison of two systemic antibiotics for the prevention of complications in elective colorectal surgery.

In a prospective randomized trial on 77 patients undergoing elective colorectal surgery, cefoxitin and cephalothin were given as systemic antibiotic prophylaxis. Postoperative sepsis occurred in 2/40 (5%) of those given cefoxitin compared to 9/37 (24.3%) of those given cephalothin. The reduction in the infection rate in the group treated by cefoxitin was statistically significant (p less than 0.02). Specific drug toxicity was not evidenced except for transient skin rashes in two patients of both groups.

Aged↗

PubMed1986

Selectivity of the cimetidine-induced alterations in the renal handling of organic substrates in humans. Studies with anionic, cationic and zwitterionic drugs.

Cimetidine reduces the renal clearances of the organic cations procainamide and n-acetylprocainamide in humans and in vitro preparations by inhibition of renal cationic proximal tubular secretion. The aim of this study was to investigate in humans the selectivity of cimetidine in altering the renal handling of three different organic ions as drug substances: anion (cephalothin), cation (ranitidine) and zwitterion (cephalexin). The study was conducted in six healthy subjects who received the above drugs as single doses with and without chronic cimetidine administration. Cimetidine had no statistically significant (P greater than .05) effect on cephalothin disposition including renal clearance, but significantly reduced the renal clearance of ranitidine by over 40% between 4 and 12 hr after administration, with a concomitant increase in ranitidine plasma concentrations and elimination half-life prolongation. In addition, the renal clearance of cephalexin was reduced by cimetidine by 27% between 1 and 2 hr, but there was no change in cephalexin plasma concentrations and elimination half-life. These findings confirmed the hypothesis that cimetidine-mediated inhibition of renal drug clearance in humans is selective for a common cationic secretory transport mechanism in the proximal tubule of the kidney, rather than a nonspecific action on renal function.

Adult↗

PubMed1979

Cardiovascular manifestations of acute antibiotic toxicity during E coli endotoxin shock in anesthetized dogs.

Surgically instrumented, pentobarbital-anesthetized dogs were used to examine the acute cardiovascular activities of gentamicin, tobramycin, sodium penicillin-G, and sodium cephalothin during a control state and during experimental circulatory shock induced by E coli endotoxin. Intravenous administration of 2.5, 5, 10, and 20 mg/kg gentamicin or tobramycin resulted in a transient (5--20-minute) state of cardiovascular depression, as reflected by dose-related decreases of systemic blood pressure, cardiac output, left ventricular pressure, dP/dt max, left ventricular contractile force, and dF/dt max; heart rate was affected little. Endotoxin produced a persistent state of circulatory depression characterized by hypotension, decreased cardiac output, arterial acidemia, and reduced indices of cardiac function. During endotoxin shock, the cardiovascular effects of gentamicin and tobramycin were relatively more pronounced (sometimes more than doubled) than effects observed during the control state. Equally large doses of penicillin or cephalothin, however, had no discernible circulatory effects in either control dogs or dogs subjected to endotoxin shock. Present data indicate that the cardiovascular toxicities of the aminoglycoside antibiotics gentamicin and tobramycin were augmented during experimental circulatory shock, and suggest the need for specific hemodynamic surveillance when intravenous administration of cardioactive antibiotics is required in patients with pre-existing circulatory dysfunction.

Animals↗

PubMed1985

How certain drugs interfere negatively with the Jaffé reaction for creatinine.

Phenacemide and cephalothin may interfere either positively or negatively with the determination of creatinine by the Jaffé reaction, depending on the analytical system. The drug-picrate chromophores maximally absorb within the first minute of reaction (21 s for phenacemide, 45 s for cephalothin), after which the absorbances decrease. Thus, these drugs negatively interfere in analytical systems involving kinetic measurements when the time interval of measurement includes the period of decreasing absorbance.

Autoanalysis↗

PubMed1979

Gentamicin and ticarcillin serum levels.

Ticarcillin disodium and gentamicin sulfate serum levels were measured one and five hours after intravenous administration. Patients receiving ticarcillin plus gentamicin had a significantly lower mean gentamicin level one and five hours after antibiotic administration than patients receiving cephalothin sodium plus gentamicin. The serum ticarcillin levels were significantly lower five hours after administration in patients receiving ticarcillin plus gentamicin than in those receiving ticarcillin plus cephalothin. Low antibiotic serum levels in patients with serious infections treated with these antibiotic combinations are of potential clinical significance; therefore, to ensure an optimal antimicrobial therapy, it is advisable to determine the drug serum concentrations (especially aminoglycoside) even in patients with normal renal function when treating with combinations of antimicrobials.

Bacterial Infections↗

PubMed1979

[Laboratory and clinical studies CS-1170 (author's transl)].

CS-1170 is a new antibiotic, a derivative of cephamycin C. In vitro, 50 strains of E. coli and Klebsiella consisting of gentamicin-sensitive isolated from the blood and gentamicin-resistant strains isolated from the urine were inhibited at concentrations from 0.4 to 12.5 mcg/ml of CS-1170, whereas only 2 strain of Klebsiella isolated from the blood had MIC more than 50 mcg/ml of the antibiotic. Moreover, CS-1170 was significantly more effective than cefazolin and cephalothin against these strains. Ten strains of gentamicin-sensitive Serratia isolated from the blood and the 2 gentamicin-resistant strains were inhibited at concentrations from 3.2 to 50 mcg/ml of CS-1170 and only one strain was resistant to this agent. All tested Serratia were resistant to cefazolin and cephalothin. CS-1170 was not effective against Enterobacter. Three cases of biliary tract infections consisting of 2 cases of cholelithiasis and a case of carcinoma of bile duct were treated with 4 g/day dosage of CS-1170. The remarkable effects were obtained in the two cases with cholelithiasis, whereas a case with the carcinoma was treated not so effectively by administration of CS-1170.

Aged↗

PubMed1979

[Comparison of four recently introduced cephalosporins with respect to probability of resistance in multiresistant strains of Escherichia coli, Proteus mirabilis and Klebsiella spec. (author's transl)].

Strains with the same number of resistances were arranged in so-called resistance classes. Nine classes of resistance (0 to greater to or equal to 8) were formed by means of ten standard chemotherapeutics; the four new cephalosporins were excluded. For every resistance class frequency of cephalosporinresistance was described as coefficient ranging from 0 to 1 (Fig. 1). In Cephalothin the coefficients were markedly rising only in 6 (7)-fold resistant strains of the species examined. Similar but somewhat reduced rising of coefficients was also observed in Cefaclor and Cefamandole. In Cefaclor this is particularly evident for E. coli, whereas in Cefamandole, it concerns Klebsiella spec. In the other species rising of coefficients of Cefaclor and Cefamandole are less marked. The probability of restance in multiresistant strains are therefore distinguished more clearly from that of Cephalothin. Cefuroxime and Cefoxitin take a special position because the probability of resistance does not rise in multiresistant strains. The coefficients of Cefoxitin do not show any recognizable dependance on multiresistance. For clinical purpose the following conclusions can be derived: Because of their effectiveness in multiresistant strains Cefoxitin and Cefuroxime are suitable for empiric use in intensive care units where many multiresistant Klebsiella-strains are to be expected. Cefamandole on the other hand is characterized by a rising probability of resistance in multiresistant strains. Therefore it should only be given after antibiotic testing. Cefaclor, a new oral cephalosporin, will be introduced specially for outpatients where multiresistant strains are rarely found.

Anti-Bacterial Agents↗

PubMed1979

[The distribution of minimal inhibitory concentrations of recently introduced cephalosporins in multiresistant strains of Escherichia coli, Proteus mirabilis and Klebsiella spec. as revealed by zone sizes of a standardized agar diffusion test (author's transl)].

Strains of a species were divided into two groups according to the number of resistances (less than or equal to 4, greater than or equal to 5) using 10 standard chemotherapeutics regularly examined, the new cephalosporins not being among them. These groups of less than or equal to 4- and greater than or equal to 5-fold resistant strains were compared for each cephalosporin tested (Fig. 1). The most different distributions of zone diameters (of both groups) were seen in Cephalothin, whereas in Cefoxitin and - with little limitations - also in Cefuroxime in the main these distributions did not differ; they covered the same field. The distributions of Cefaclor and Cefamandole took an intermediate position. With respect to the two groups similar observations were made for E. coli, proteus mirabilis and Klebsiella spec. The differences between the two groups were most marked in Klebsiella strains. E. coli exhibited the smallest differences (Fig 1). On the assumption that the distribution of zone diameters reflect that of MIC's it can be concluded that nearly all of the Cefaclor- and Cefamandole-sensitive multiresistant strains have more elevated MIC's than those with only less than or equal to 4 resistances. On the other hand it must not be expected that MIC'S OF Cefoxitin and Cefuroxim are rising in multiresistant strains. It could be demonstrated that the different qualities of the recently introduced cephalosporins revealed in multiresistant strains can be explained by different dependences on mechanisms of Cephalothin-resistance (Fig. 2). This resistance is much more frequent in greater than or equal to 5-fold resistant strains. Recommendations for clinical use derived from these results are discussed.

Cefaclor↗

PubMed1979

In vitro activity and pharmacokinetics of cefaclor in normal volunteers and patients with renal failure.

In both Mueller-Hinton agar (MHA) and antibiotic medium no. 1 (AB1) cefaclor was more active than cephalothin or cephalexin against Enterobacteriaceae. Its activity was equivalent to cephalexin against S. aureus in MHA. Cefaclor was particularly active against P. mirabilis. The activity of this antibiotic was greated in AB1 than in MHA. The inoculum effect was pronounced for cefaclor when compared with cephalothin, but cefaclor retained greater activity even against the higher inoculum. In volunteers with normal renal function, cefaclor produced slightly lower blood levels than those reported for cephalexin. Absorption after eating was decreased and delayed. Despite severe renal failure, substantial urine levels of antibiotic were still achieved. In contrast to cephalexin, plasma half-life for cefaclor was only moderately prolonged by renal failure (two-to-threefold) and only minimally shortened by haemodialysis. Adequate concentrations of cefaclor in sputum, active against common respiratory pathogens, could not be consistently demonstrated after the oral administration of a 1 gram dose of cefaclor.

Adult↗