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Genus identification and antibiotic susceptibility patterns of bacterial isolates from cows with acute mastitis in a practice population.

OBJECTIVE: To determine frequency and antibiotic susceptibility patterns of bacterial pathogens from cows with mastitis treated at a private practice during a 2-year period. DESIGN: Observational study. ANIMALS: Lactating dairy cows from 47 herds of 40 to 600 cows each. PROCEDURE: Bacteria isolated from milk samples were identified as coliforms, Staphylococcus spp, or Streptococcus spp, using selective media. Antibiotic susceptibility testing was performed, using the disk diffusion method with the following antibiotics: gentamicin, amikacin sulfate, penicillin G, penicillin G-novobiocin, ampicillin, cephalothin sodium, ticarcillin, ceftiofur, lincomycin, erythromycin, pirlimycin hydrochloride, sulfonamide, tetracycline, and polymyxin B. RESULTS: Of 354 samples tested, 82 (23.2%) yielded no growth. Of bacteria isolated, 54 (15.3%) were coliforms, 96 (27.1%) were Staphylococcus spp, and 94 (26.6%) were Streptococcus spp. Antibiotic susceptibility testing was performed on 62.4% of all samples cultured. For Staphylococcus isolates, cephalothin was the most effective antibiotic in vitro for which a commercially available preparation exists. Penicillin G-novobiocin was the most effective antibiotic in vitro for Streptococcus isolates. Commercial antibiotic preparations approved for intramammary use were not effective in vitro against coliforms that were found to cause mastitis. CLINICAL IMPLICATIONS: Mastitis caused by coliform organisms does not respond to commercial preparations intended for intramammary use; however, it may respond to parenterally administered antibiotics. Mastitis caused by Staphylococcus spp or Streptococcus spp should be treated first with a cephalothin or penicillin G-novobiocin preparation.

Acute Disease↗

MICROBIOLOGICAL ACTIVITIES OF LYSOSTAPHIN AND PENICILLINS AGAINST BACTERIOPHAGE 80/81 STRAINS OF STAPHYLOCOCCUS AUREUS.

Using 20 clinical isolates of S. aureus (all bacteriophage 80/81 type), we found that lysostaphin inhibits the growth of all cultures at concentrations significantly lower than those observed with any of eight penicillins, a penicillin-like compound (cephalothin), or fusidic acid (a steroid antibiotic). All test cultures were shown to be resistant to penicillin G, ampicillin, and propicillin. Of the remaining penicillins (all penicillinase-insensitive), oxacillin, nafcillin, cloxacillin, and cephalothin were approximately equal in antimicrobial activity. Ancillin was slightly less active, and methicillin was even lower in potency. Cultures varied more widely in susceptibility to fusidic acid. None of the clinical isolates tested was found to be resistant to lysostaphin.

Ampicillin↗

INDUCTION BY ANTIBIOTICS AND COMPARATIVE SENSITIVITY OF L-PHASE VARIANTS OF STAPHYLOCOCCUS AUREUS.

Molander, C. W. (Cedars of Lebanon-Mount Sinai Hospitals, Los Angeles, Calif.), B. M. Kagan, H. J. Weinberger, E. M. Heimlich, and R. J. Busser. Induction by antibiotics and comparative sensitivity of L-phase variants of Staphylococcus aureus. J. Bacteriol. 88:591-594. 1964.-The penicillins, cephalothin, vancomycin, and bacitracin were found to be less inhibitory to the L-phase variants than to their respective parent bacteria. Those antibiotics not considered to be primarily inhibitors of cell-wall synthesis were, in general, somewhat more inhibitory to the L form than to their parent bacteria. Only the penicillins and cephalothin readily induced L-phase variation. Novobiocin induced pleomorphic growth resembling the earliest stages of L-phase transformation. Failure of observable induction by bacitracin and vancomycin suggests that these two antibiotics affect cell-wall synthesis in a manner different from the penicillins, or that L-phase transformation may require more than "penicillin-like" interference with cell-wall synthesis.

Anti-Bacterial Agents↗

Quantitative antibiotic sensitivity determinations of Staphylococcus aureus isolated from eye cultures.

The sensitivities of 108 strains of Staphylococcus aureus, isolated from patients with a variety of ocular conditions, were tested quantitatively against nine antibiotics by means of a microtiter broth-dilution method. Of the nine antibiotics, cephalothin sodium had the lowest (and therefore the best) minimum bactericidal concentration (MBC) and minimum inhibitory concentration (MIC). The MBC and MIC of gentamicin sulfate were very close to those of cephalothin. The MBCs and MICs of erythromycin, ampicillin sodium, penicillin, tetracycline, methicillin sodium, and carbenicillin disodium were moderately good. Chloramphenicol had the poorest response.

Anti-Bacterial Agents↗

Recontamination after gastrointestinal decontamination with non-absorbable antibiotics.

In an attempt to restore the colonization resistance we administered anaerobic microflora to prevent an abnormal colonization of the intestine after antibiotic treatment had been discontinued. After the antibiotics had been discontinued and before the donor flora had been administered and had colonized the intestine, microorganisms present were "unopposed" and expanded to a high density. A mouse model was used to investigate which antibiotics negatively influenced the donor flora and reduced the colonization resistance when administered intraperitoneally. Erythromycin, clindamycin and carbenicillin suppressed the donor flora permanently, as could be seen by the reduced colonization resistance. Benzylpenicillin, ampicillin, doxycycline and the combination gentamicin-cephalothin affected the colonization resistance as long as these agents were present. Gentamicin alone and cephalothin and oxytetracycline had no effect on the colonization resistance.

Absorption↗

Beta lactamase resistance of newer cephalosporins and antimicrobial effectiveness against gram-negative bacilli.

Three newer cephalosporins (cefamandole, cefoxitin and cefazaflur) were investigated, in comparison with three older agents (cephalothin, cephaloridine and cefazolin) to determine their stability to beta-lactamases of gram-negative bacilli, and to correlate this with their antibacterial activity. Nine of the 17 bacterial strains employed produced broadspectrum beta-lactamases; the remaining eight produced cephalosporinases. The cephalosporins were highly active against bacteria producing broad-spectrum beta-lactamases; they were less active against organisms producing cephalosporinases. All of the cephalosporinase-producing strains were resistant to cephalothin anc cephaloridine. With the other cephalosporins the correlation between hydrolysis by cephalosporinases and resistance of the organisms was poor. Four to eight cephalosporinase-producing strains were resistant to cefoxitin, which was completely resistant to hydrolysis by the beta-lactamases. Cefozolin, cefamandole and cefazaflur inhibited several of these strains in spite of destruction by the beta-lactamase. Several cephalosporins need to be used in antimicrobial susceptibility testing of gram-negative bacilli.

Amidohydrolases↗

[Has the rate of resistant staphylococci increased recently? (author's transl)].

In clinical material sent to the Clinic for Chemotherapy and the Institute of Hygiene of Vienna University between 1973 and 1978, Staphylococcus aureus was isolated from 0.9-2.3% and 4.2-11.9% respectively. The rate of resistance of the clinic material to oxacillin increased from 0.8 to 16.0%, to cephalothin from 3.3 to 30.5%, to gentamicin from 0.0 to 43.3%, and to erythromycin from 0.8 to 40.2%. In material sent to the Institute of Hygiene the rate of resistance to oxacillin was stable at 13.8%, and to cephalothin remained fairly constant at 2.4%. On the other hand, the rate of resistance to gentamicin increased from 0.5 to 48.5%, and to erythromycin from 19.8 to 56.9%. The reasons for these alarming increases in resistance and the conclusions which should be drawn are discussed.

Austria↗

[In vitro testing of newer cephalosporins (author's transl)].

The spectrum of activity of the newer cephalosporins is considerably wider and includes a number of gram-negative bacteria. Test results using cephalothin as 'class disc' of a class of antibiotics is therefore no longer valid for the newer members. Like cefazoline, all of the above-mentioned antibiotics are more effective against Escherichia coli. Cefuroxin and cefoxitin also display increased effectiveness against Klebsiella, as do cefoxitin against Serratia and indolpositive Proteus species, and cefamandole and cefuroxime against Enterobacter. Cefotaxim is superior to all other agents, as was also demonstrated in our own inhibition zone tests; in addition cefotaxim is effective against Pseudomonas aeruginosa. Since the various pathogens do not exhibit a uniform pattern of resistance to these antibiotics, the four new agents should for the time being be tested independently of cephalothin and cefazoline.

Cefamandole↗

Anaerobic bacteria: evaluation of disc susceptibility to four cephalosporins.

The disc diffusion technique was evaluated with 178 strains of anaerobes and four cephalosporins (cephalothin, cefamandole, cefazolin and cefoxitin). Good correlation in results was found in comparison with the agar dilution technique (p less than 0.001) with the exception of cefamandole and cefazolin against anaerobic cocci (p greater than 0.05). Choosing a breakpoint of 8 microgram/ml for distinguishing susceptible and resistant strains, we determined corresponding incubation, the rate of error is less than 1% for false susceptible and less than 5% for false resistant. However, some strains of anaerobic cocci required a 48 hour incubation period for allowing visible growth. Moreover, a great deal (60.5%) of overlapping zone diameters made interpretation of disc diffusion test difficult among Bacteroides fragilis strains classed as susceptible, intermediate and resistant occuring with cefoxitin. The results have shown that the cephalothin disk will not accurately predict susceptibility of B. fragilis to cefoxitin.

Bacillaceae↗

[Bacteriological investigations with a new Semisynthetic oxy-beta-lactam antibiotic LY 127935 (AUTHOR'S TRANSL)].

The antimicrobial activity of a new oxy-beta-lactam antibiotic LY 127935 against 1066 strains of gram-negative and gram-positive bacterial was evaluated in comparison to cephalothin. The antibiotic has a very wide spectrum and is exceptionally active, in particular against gram-negative rods. It is also active against multiresistant problem strains found in intensive care units (Enterobacter cloacae, Serratia marcescens, indole-positive Proteus), and proved to be quite effective against Pseudomonas aeruginosa. Although LY 127935 is effective against Staphylococcus aureus, cephalothin is superior. Its use is not indicated against Streptococcus faecalis.

Bacteria↗

Synergy between the iron chelator deferoxamine and the antimicrobial agents gentamicin, chloramphenicol, cefalothin, cefotiam and cefsulodin.

Synergy between the iron chelator deferoxamine in the presence or absence of ascorbic acid and gentamicin, chloramphenicol, cephalothin, cefotiam or cefsulodin, used against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Klebsiella pneumoniae, proteus mirabilis and species of Salmonella, Enterobacter, Pseudomonas and Providencia, was determined by measuring the effect of the drugs and combination of drugs on growth of the bacteria in an automated turbidimeter. The combination of drugs was considered to be synergistic when the growth inhibiting effect of the combination was greater than that of the combined action of each of the drugs separately. Deferoxamine plus ascorbic acid together with either gentamicin or cefsulodin showed synergy in 10 out of 10, and 5 out of 6 cultures respectively, whereas deferoxamine plus ascorbic acid with chloramphenicol, cephalothin or cefotiam was synergistic in 6 out of 14, 5 out of 11, and 3 out of 6 cultures. This synergistic effect was much lower when microorganisms were incubated with deferoxamine combined with the various antibiotics but without ascorbic acid. Ascorbic acid alone had no synergistic effect. When deferoxamine was saturated with iron, its antibacterial effect was completely abolished.

Alcaligenes↗

Penetration of antimicrobial agents into bronchial secretions.

The entry of ampicillin, cephalothin and gentamicin into traceobronchopulmonary secretions/exudates was assessed in 22 patients during 28, episodes of pneumonia or bronchitis. Specimens were collected from the lower respiratory tract via tracheostomies or endotracheal tubes using either the flexible fiberoptic bronchoscope (50 specimens) or an intratracheal catheter (59 specimens). Venous blood was obtained at the same time. The concentrations in the bronchial specimens were less than those in the corresponding serums, amounting to about 10 per cent with ampicillin, 25 per cent with cephalothin and equal to or greater than 40 per cent with gentamicin.

Adult↗

Granulocytopenia in hospitalized patients. II. A prospective comparison of two antibiotic regimens in the empiric therapy of febrile patients.

The results of empiric antibiotic therapy in 126 hospitalized patients with fever during 192 episodes of granulocytopenia were studied. Febrile granulocytopenic patients were randomly allocated to receive either carbenicillin, methicillin and gentamicin, or carbenicillin and cephalothin. The response rate for the two antibiotic regimens was similar, 49 (60 per cent) of 81 responded to the former and 42 (54 per cent) of 78 to the latter. The response rate in patients receiving other antibiotics because of specific indications or counterindications was 19 (58 per cent) of 33. Thirty-nine (35 per cent) of 110 patients who responded to initial antibiotic therapy had an increase in circulating granulocytes of one log10 or more compared to only 10 (12 per cent) of 79 nonresponders with such an increase. The mortality rate in adult patients receiving carbenicillin, methicillin and gentamicin was eight (16 per cent) of 51, compared to 18 (37 per cent) of 49 in those receiving cephalothin and carbenicillin (P less than 0.05). The significance of this difference in the initial response rate or mortality rate between patients treated with the two antibiotic regimens when only patients with documented bacterial infection were considered. Patients who responded to their initial antibiotic regimen, and patients for whose fever no explanation was found, had the best prognosis.

Adolescent↗

In vitro models for the study of combination antibiotic therapy in neutropenic patients.

Neutropenic patients are at risk of serious infection caused by gram-negative bacilli and staphylococci. The mortality rate associated with gram-negative bacteremia in these patients is extremely high, especially in those with persistent and profound granulocytopenia. In these latter patients, the best results have been obtained by administering combinations of antibiotics in which both agents are active and/or show in vitro synergism against the infecting organism. Most combinations include an aminoglycoside such as amikacin and a broad-spectrum beta-lactam antibiotic, such as azlocillin, mezlocillin, piperacillin, or ceftazidime. The International Antimicrobial Therapy Project Group of the European Organization for Research and Treatment of Cancer has completed several studies evaluating various antibiotic combinations in the empiric treatment of febrile neutropenic patients. These trials have evaluated cephalothin plus gentamicin, carbenicillin plus gentamicin, and cephalothin plus carbenicillin; carbenicillin plus amikacin and carbenicillin plus amikacin plus cefazolin; azlocillin plus amikacin, ticarcillin plus amikacin, and cefotaxime plus amikacin; and azlocillin plus amikacin versus ceftazidime plus long- or short-course amikacin. The preclinical evaluation of antibiotic combinations usually involves the in vitro testing of antibiotics alone and in combination by the checkerboard method or with the use of time-kill curves. However, these methods expose the bacterial culture to a static or constant concentration of the drugs. During the in vivo treatment of infections, bacteria are exposed to changing concentrations of antibiotics, which are contingent on the individual pharmacokinetics of these drugs. We have designed a two-compartment in vitro pharmacokinetic model that allows the simultaneous study of the activity of two antibiotics with similar or different half-lives against a number of bacteria. Amikacin and azlocillin have been studied alone and in combination in this model against Pseudomonas aeruginosa, a frequent cause of bacteremia in neutropenic patients. In pharmacologically relevant doses, amikacin alone produced rapid bacterial killing, followed by regrowth of resistant subpopulations. Azlocillin alone produced a more gradual reduction of the bacterial inoculum, with ultimate bacteriostasis. Amikacin plus azlocillin produced rapid and complete eradication of the organism. In vitro pharmacokinetic models may prove to be more predictive of clinical outcome than are traditional static in vitro methods used to study antibiotic combinations.

Agranulocytosis↗

The efficacy of prophylactic antibiotics in cesarean section.

The objective of this investigation was to determine the effectiveness of cefazolin-cephalothin administration as a prophylactic regime in patients undergoing cesarean section. The study was to randomized, double-blind, placebo-controlled investigation. Cefazolin, 1.0 gm or placebo was administered intramuscularly on call to the operating room, and cephalothin, 2.0 gm, or placebo was administered intravenously at 6, 12, and 24 hours postoperatively. Ninety-five patients were included in the study with 49 in the placebo group and 46 in the drug group. Nineteen patients developed 28 infections in the placebo group while eight patients developed eight infections in the drug group (P = less than 0.05). Eight patients in the placebo group developed infections at two or more sites whereas no patient in the drug-treated group developed multiple infections. No infant developed infection and no overgrowth of bacteria occurred. This study supports the concept of preoperative antibiotic administration being beneficial to the obstetric patient.

Anti-Bacterial Agents↗

Perioperative cephalosporin prophylaxis in cesarean section: effect on endometritis in the high-risk patient.

A total of 120 patients who were to be delivered by cesarean section and who were at high risk of postoperative infection received three doses of either cefamandole, cephalothin or placebo perioperatively. Maternal serum levels for both antibiotics were in the therapeutic range. Although both drugs reduced the incidence of febrile morbidity and endometritis, only cefamandole significantly reduced the fever index. Risk factors for postoperative infections were the presence of ruptured membranes, labor, and internal fetal monitoring. Cefamandole beneficially influenced all risk factors while cephalothin was able to reduce only the risk of ruptured membranes. When a new method for obtaining endometrial tissue was utilized, 50% of cultures were negative. There was no difference in the organisms isolated from patients with and without endometritis.

Adult↗

Human vitreous levels of selected antistaphylococcal antibiotics.

Staphylococcus epidermidis and S. aureus are the most common causes of bacterial endophthalmitis. A study of the penetration of selected antistaphylococcal antibiotics into human vitreous was undertaken in 58 patients. After 2-g intravenous doses of cephalothin, cefazolin, methicillin, oxacillin, or nafcillin were given to patients about to undergo vitreous surgery, mean vitreous levels for each antibiotic were as follows: cephalothin, 0.97 microgram/ml in diabetics and 0.69 microgram/ml in nondiabetics; cefazolin, 0.84 microgram/ml in diabetics and 1.6 microgram/ml in nondiabetics; methicillin, 2.56 micrograms/ml in diabetics and 2.64 micrograms/ml in nondiabetics; oxacillin, 0.62 microgram/ml in diabetics and 0.34 microgram/ml in nondiabetics; and nafcillin, 0.73 microgram/ml in diabetics and 0.75 microgram/ml in nondiabetics. Only cefazolin produced vitreous concentrations consistently above its minimum inhibitory concentration for 90% of S. epidermidis isolates. Staphylococcus aureus isolates were not similarly covered. There was a trend toward higher vitreous antibiotic concentrations in patients with proliferative vitreoretinopathy and rubeosis.

Anti-Bacterial Agents↗

Secretion of beta-lactam antibiotics in pure human pancreatic juice.

The secretion of cephalothin and cefoxitin in stimulated pure pancreatic juice was studied in 13 persons after intravenous administration of antibiotics. Of all these studied, three had acute relapsing pancreatitis, five chronic pancreatitis, and five were control subjects. Antibiotic levels were measured in paired pure pancreatic juice and serum samples at fixed time intervals after administration. Cephalothin was detected in very low levels (1 to 1.8 micrograms/ml) in the pure pancreatic juice of four of the six persons studied (3 micrograms/ml). Although therapeutic levels were not obtained in stimulated pure pancreatic juice with either antibiotic, additional studies evaluating antibiotic levels in unstimulated pure pancreatic juice and in pancreatic tissue would be helpful in assessing the role of antibiotic therapy in the treatment of pancreatitis.

Acute Disease↗