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Randomized, prospective comparison of first- and second-generation cephalosporins as infection prophylaxis for cardiac surgery.

Surgical wound infections after cardiovascular surgery may be life threatening and are resource intensive. Second-generation cephalosporins are purported to have a broader antimicrobial spectrum than first-generation cephalosporins and, therefore, may be more efficacious for infection prophylaxis. We have conducted a randomized prospective study of 702 patients undergoing open heart surgery to test the hypothesis that the second-generation cephalosporin, cefuroxime, will be more efficacious for infection prophylaxis than the first-generation cephalosporin, cefazolin. Patients were randomized to receive cefazolin 1 g intravenously every 8 hours for 48 hours begun 1 hour preoperatively plus 1 g after 4 hours of surgery (8 doses, n = 425) or cefuroxime 1.5 g 1 hour prior to surgery plus 1.5 g every 12 hours for 3 additional doses (4 doses, n = 277). Infection was defined as a draining wound with or without a positive culture. There was no difference in the wound infection rate between the groups (p = 0.68). Chest wound infections occurred in 2.1% of patients treated with cefazolin and 2.9% of patients treated with cefuroxime (p = 0.79). The rate of true mediastinitis requiring exploration and drainage was 0.7% in both groups (p = 0.084). Leg infections occurred in 6.6% of cefazolin-treated patients and 5.6% of cefuroxime-treated patients (p = 0.83). The second-generation cephalosporin, cefuroxime, did not reduce the incidence of wound infection when compared with the first-generation cephalosporin, cefazolin. Since institutional antibiotic acquisition and administration costs vary, careful analysis of these factors will allow determination of the most cost-effective infection prophylaxis regimen in cardiac surgery.

Cardiac Surgical Procedures↗

Effects of prophylactic antibiotics on endometrial flora in women with postcesarean endometritis.

OBJECTIVE: To determine the effect of prophylactic antibiotics on endometrial and endocervical microflora upon diagnosis of postcesarean endometritis. METHODS: The medical records of patients enrolled in open-label comparative trials of therapeutic antibiotics for postpartum endometritis between 1989 and 1994 were reviewed (n = 682). Endometritis was diagnosed by a standard definition that included fever and localizing signs. Endometrial cultures were obtained by a sheathed injection/aspiration technique. Aerobes and anaerobes were isolated by standard microbiologic techniques. The primary outcome, endometrial and endocervical microflora, was compared in women who received intravenous ampicillin (2 g every 6 hours for 1-3 doses), cephalosporin (2 g every 6 hours for 1-3 doses), or no prophylaxis. Secondary outcomes included the cure of endometritis and the prevalence of wound infection in the three groups. RESULTS: Four hundred sixty-five of 682 patients (67%) had a cesarean delivery. One hundred fifty-one patients received ampicillin prophylaxis, 100 patients received cefazolin prophylaxis, 18 patients received extended-spectrum antibiotics, and 196 patients received no prophylaxis. Patients who received cefazolin prophylaxis had a significant increase in enterococcus (P < .05) and a significant decrease in Proteus species (P < .05) from endometrial samples. Patients who received ampicillin prophylaxis had a significant increase of Mycoplasma species (P < .05), Klebsiella pneumoniae (P < .0001), Escherichia coli (P = .04), and any aerobic gram-negative rod (P = .003) from endometrial samples. Ampicillin prophylaxis was associated with a decrease in Prevotella bivia (P < .05) and any anaerobe (P < .01). Endometritis cure rates were similar between prophylaxis groups and between prophylaxis and treatment groups. However, the cefazolin prophylaxis followed by cephalosporin treatment was associated with more wound infections (19%) than other prophylaxis and treatment groups, (6%, P < .01). CONCLUSION: Ampicillin and cefazolin prophylaxis alters endometrial and endocervical microflora of women who develop endometritis. Whereas these changes had no effect on endometritis cure rate (power > 80%), the association between cefazolin prophylaxis followed by an extended-spectrum cephalosporin and wound infection may warrant caution against the use of the combination.

Adult↗

In vitro potency and stability of fortified ophthalmic antibiotics.

PURPOSE: This study evaluates the in vitro potency, stability and contamination of the fortified ophthalmic antibiotic preparations of cefazolin, vancomycin, gentamicin and tobramycin stored for 4 weeks. The effects of the different solvents and storage temperatures on the antimicrobial potency and stability were also examined. METHODS: The fortified stock solution of cefazolin and vancomycin were prepared by reconstituting with 0.9% sodium chloride and with artificial tears. Gentamicin and tobramycin were prepared by adding parenteral forms into their commercial ophthalmic solutions. The antimicrobial potency was measured by the minimum bactericidal concentration for cefazolin (33.3 mg/mL) and vancomycin (31 mg/mL) against Staphylococcus aureus, and for tobramycin (13.5 mg/mL) and gentamicin (13.5 mg/mL) against Pseudomonas aeruginosa. The stability of solution was evaluated by measuring absorbance spectra and pH. During the study period the levels of contamination of the stock solutions were examined by culturing on blood and on Sabouraud-dextrose media. RESULTS: There were no differences in the antimicrobial potency of the cefazolin, vancomycin and tobramycin within the 4-week period; however, the potency of gentamicin was decreased at both temperatures after 21 days. It was found that different solvents or storage temperatures had no effect on the potency. Throughout the 4-week period, no change was found in the absorbance spectra of gentamicin and tobramycin, whereas the absorbance spectra of cefazolin and vancomycin stored at 24 degrees C increased in both of the solvents used (P<0.05). In all of the antibiotics, pH changed at 24 degrees C after 7-10 days; however, at 4 degrees C, only the pH of tobramycin exhibited changes after 14 days (P<0.05). No contamination was detected in the stock solutions during the study period. CONCLUSION: Topical fortified antibiotic solutions used for longer than 7 days should be stored at < or =4 degrees C, those stored at 24 degrees C should be discarded after 7 days.

Anti-Bacterial Agents↗

In vitro evaluation of antibiotic elution from polymethylmethacrylate (PMMA) and mechanical assessment of antibiotic-PMMA composites.

OBJECTIVE: To determine whether different methods of sterilization of antibiotic vials or the heat of polymerization altered the antimicrobial activity or mechanical properties of antibiotic/polymethylmethacrylate (PMMA) composites when compared to antibiotic-free PMMA. STUDY DESIGN: In vitro study. METHODS: Steam-sterilized, gas-sterilized, and non-sterilized 1 gram vials of cefazolin and injectable gentamicin sulfate (high and low doses) were mixed with PMMA to prepare composites for antibiotic elution evaluation, compression, and elongation testing. Blocks of PMMA that contained antibiotic were assayed for antibacterial activity using an agar gel diffusion method or were placed in phosphate buffered saline (PBS) to assess elution of antibiotic. Phosphate buffered saline samples from steam-sterilized cefazolin and high-dose gentamicin groups were assayed on days 1, 2, 5, and 9 for cefazolin or gentamicin concentration by high-pressure liquid chromatography or fluorescent polarization immunoassay, respectively. RESULTS: PMMA blocks containing antibiotic inhibited bacterial growth of Staphylococcus aureus 25923 for an average of 9 days. Cefazolin and gentamicin concentration in PBS decreased dramatically after the first 24 hours, but remained above minimum inhibitory concentration (MIC) throughout the experiment for all groups except low-dose gentamicin. Compressive strength of plugs made from plain cement and plugs made from PMMA mixed with untreated and steam-sterilized cefazolin was similar, but was significantly different from the other groups. There appeared to be an inverse relationship between compressive strength and elongation. CONCLUSION: PMMA/antibiotic composites inhibited bacterial growth for 7 to 10 days. Compressive strength was affected by different additions of antibiotic. CLINICAL RELEVANCE: Bacteria introduced during a surgical procedure may be inhibited by elution of antibiotic from PMMA at the time of contamination.

Animals↗

Antimicrobial therapy of septicemia due to Klebsiella pneumoniae in neutropenic rats.

Three different isolates of Klebsiella pneumoniae, highly sensitive to amikacin but varying in susceptibility to cefazolin, were injected intraperitoneally into neutropenic rats. Animals were treated every 8 hr for 72 hr with saline (controls), cefzolin (full dose, 40 mg/kg; one-fourth dose, 10 mg/kg), amikacin (full dose, 8 mg/kg; one-fourth dose, 2 mg/kg), or a combination of both drugs at either full dose or one-fourth dose. All drugs were given intramuscularly. Combination therapy with full doses produced higher mean bactericidal titers in serum and more rapid clearance of bacteria from blood and peritoneal washings. However, cumulative mortality at 72 hr in rats treated with amikacin plus cefazolin in full doses (24%, 23%, and 44%) was not significantly different from mortality in rats treated with amikacin alone (34%, 17%, and 62%). Results with cefazolin alone were not significantly different from the mortality in control animals for two of the three challenge organisms. When the minimal inhibitory concentration of cefazolin was less than or equal to 8 micrograms/ml, in vivo synergy was suggested by the similar survival rate obtained with a combination of a one-fourth dose of each agent and with amikacin alone in a full dose. These results demonstrate the relative ineffectiveness of cefazolin for therapy of klebsiella septicemia and suggest that in vivo antimicrobial synergy occurs in combination therapy against strains of bacteria relatively sensitive to cephalosporins.

Agranulocytosis↗

Topical ciprofloxacin versus topical fortified antibiotics in rabbit models of Staphylococcus and Pseudomonas keratitis.

We tested the antibacterial activity of ophthalmic 0.3% ciprofloxacin against that of 5.0% cefazolin and 1.36% tobramycin in two experimental models of keratitis, using a methicillin-sensitive strain of Staphylococcus aureus and an aminoglycoside-sensitive strain of Pseudomonas aeruginosa, respectively. Both corneas of New Zealand white rabbits were intrastromally injected with either S. aureus or P. aeruginosa. Twenty-four hours later, each eye was topically treated hourly for 24 hours. In the S. aureus model, the control group received Tears Naturale Free (Alcon Laboratories, Inc., Fort Worth, TX), the ciprofloxacin group received 0.3%, ciprofloxacin and the cefazolin group received 5.0% cefazolin. In the P. aeruginosa model, the control group received Tears Naturale Free, the ciprofloxacin group received 0.3% ciprofloxacin, and the tobramycin group received 1.36% tobramycin. One hour after the last eyedrops were administered, the rabbits were killed, and their corneas were processed for quantification of bacteria. For the S. aureus model, the mean (+/- SEM) colony forming units (CFU) of the control, 7.1 x 10(6) (+/- 4.0 x 10(6)); ciprofloxacin, 6.4 x 10(2) (+/- 1.6 x 10(2)); and cefazolin, 1.3 x 10(3) (+/- 1.8 x 10(2)) groups were different (F = 17.5; p = 0.001). The ciprofloxacin and cefazolin groups were not different from each other (p = 0.034). The mean (+/- SEM) CFU for the control group in the P. aeruginosa model was 2.8 x 10(8) (+/- 1.7 x 10(7)). All corneas in the ciprofloxacin and tobramycin groups were sterile.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗

Perioperative antibiotics in major elective gynecologic surgery.

The efficacy of a three-dose, perioperative regimen of cefazolin or placebo in reducing postoperative infectious morbidity was evaluated in a double-blind study in 206 patients undergoing elective vaginal or abdominal hysterectomy. Postoperative infectious morbidity was defined as: an oral temperature of 100.4 F (38 C) or greater on any two postoperative days (excluding the first day), positive bacteriologic cultures, or pus from a wound. In premenopausal patients, cefazolin significantly reduced the incidence of postoperative infectious morbidity; 19% of the cefazolin group who had abdominal hysterectomy had evidence of infection compared to 71% of the placebo group, and 10% of the cefazolin group who had vaginal hysterectomies had evidence of infection compared to 37% of the placebo group. In postmenopausal patients undergoing abdominal hysterectomy, cefazolin also reduced the incidence of postoperative infection compared to placebo, but the difference was not significant (20% compared to 37%).

Adult↗

Use, misuse, and cost of parenteral cephalosporins at a county hospital.

We reviewed total usage of parenteral cephalosporins at a county hospital during 1978 with regard to appropriateness, pattern of use, and cost. In addition, we determined the impact of replacing cephalothin with cephapirin in the hospital formulary. During the 12-month study 366 patients received 409 courses of parenteral cephalosporins: 167 received cefazolin, 160 received cephapirin, and 35 received a combination of cefazolin and cephapirin. The surgical service prescribed 87% of the cephapirin and 92% of the cefazolin. Parenteral cephalosporins were used 62% of the time for prophylaxis and 38% of the time for therapy. Usage was judged inappropriate in 47% of all courses based on our criteria; 25% of the therapeutic courses were judged inappropriate, compared to 60% of the prophylactic courses. Pharmacy costs of cefazolin used as prophylaxis were more than twice the cost for cephapirin. Cost of a mean therapeutic course for cefazolin was 43% higher than for cephapirin. Antibiotic audits and continued education combined with judicial substitution of therapeutic equivalents should limit the inappropriate use and expense of parenteral cephalosporins for large as well as small hospitals.

Cefazolin↗

In vitro activity and pharmacokinetics in patients of cefamandole, a new cephalsoporin antibiotic.

Cefamandole nafate, a new cephalosporin for parenteral use, was evaluated in vitro against 231 recent clinical isolates and in 12 patients. Cefamandole had activity equivalent to cefazolin against Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae. Cefamandole was more active than cephalothin or cefazolin against Proteus mirabilis. Both cefamandole and cefazolin were as active as cephalothin against S. aureus, were slightly more active against K. pneumoniae, and were considerably more active against E. coli. All strains of indole-positive Proteus sp. were inhibited by 6.3 mug of cefamandole per ml but only 20% were inhibited by 25 mug of cefazolin or cephalothin per ml. Eighty-eight percent of Enterobacter sp. was inhibited by 25 mug of cefamandole per ml, but only 20 and 5% were inhibited by the same concentration of cefazolin and cephalothin, respectively. Peak levels of cefamandole ranged from 6.0 to 110 mug/ml in serum and levels ranged from 440 to 16,800 mug/ml in a 4- to 6-h collection of urine after a 500-mg or 1-g intramuscular dose (6.1 to 17.3 mg/kg) in patients with endogenous creatinine clearances of >/=31 ml/min. These levels were done after the first dose, at mid-therapy, and at the end of therapy. There was no evidence of accumulation with the 500-mg or 1-g dose given every 4 to 6 h. The percentage of the dose excreted in the urine within the first 4 to 6 h after administration of cefamandole was >/=43%. The half-life of cefamandole in serum was 49 to 126 min.

Bacteria↗

Distribution in normal and inflammatory tissue of a new semisynthetic cephalosporin, SK&F 75073.

SK&F 75073 is a new cephalosporin with broad spectrum antibacterial activity. SK&F 75073-14C and cefazolin-35S were administered separately to groups of rats as a single intramuscular dose of 20 mg/kg. Tissues with highest drug levels 15 minutes following dose were as follows: (SK&F 75073/cefazolin levels), kidney - 86/70 microgram/g, liver - 33/22 microgram/g, lung - 29/17 microgram/g, heart - 23/10 microgram/g, adrenal - 13/7 microgram/g. Plasma levels at peak were 134 microgram SK&F 75073/ml (half-life, 1.9 hours) and 72 microgram cefazolin/ml (half-life, 0.75 hours). Dose excreted in 24 hours was: SK&F 75073, urine 66% and feces 27%; cefazolin, urine 96% and feces 2%. Both antibiotics were also administered, at 20 mg/kg, to rats with the carrageenan-induced inflammatory pouches. Exudate from these pouches contained from 2 to 10 times more SK&F 75073 than cefazolin. Radioassay and bioassay of these substances in the exudate gave similar results. Serum protein binding ranged from 96 approximately 98% for SK&F 75073 and 34 approximately 69% for cefazolin. Data indicated that highly protein bound SK&F 75073 enters tissues and tissue fluid to a greater extent than the lesser bound but therapeutically proven antibiotic agent cefazolin.

Animals↗

Phospholipid bilayer permeability of beta-lactam antibiotics.

Liposomes containing penicillinase or cephalosporinase were prepared from the phospholipids of Escherichia coli. After free beta-lactamase was inactivated by clavulanic acid or penicillanic acid sulfone followed by separation of inactivated enzyme and inhibitor from liposomes by gel filtration, the permeability of these liposomes to ampicillin, cefazolin and cephaloridine was estimated by measuring the hydrolysis of these antibiotics by the entrapped enzymes. The permeability parameter C (minute-1 microM lipid-1) of ampicillin, cefazolin and cephaloridine was calculated to be 2.35 X 10(-4), 0.33 X 10(-4) and 0.52 X 10(-4), respectively. The lipid bilayer permeability of these antibiotics was also measured by using the liposomes containing these antibiotics. About half of the initially entrapped ampicillin was released from the liposomes within 80 minutes, while no significant release of cefazolin and cephaloridine could be detected during the same period. These results clearly indicates that the lipid bilayer membrane is more permeable to ampicillin than cefazolin and cephaloridine, and they are consistent with the observations of Sawai et al., who showed that ampicillin was a more effective antibacterial drug than cefazolin and cephaloridine against the porin-deficient mutants.

Ampicillin↗

[Hyperosmotic glucose and antibiotics induce production of plasminogen activator inhibitor and expression of TGF beta mRNA by rat peritoneal mesothelial cells].

To investigate the mechanism of fibrosis in peritoneal dialysis, we observed the effects of the hyperosmotic glucose and antibiotics such as gentamicin and cefazolin on rat peritoneal mesothelial cells with cell culture, fibrin-plate lyzing and Northern blotting analysis method. The peritoneal mesothelial cells may express PAI-1 mRNA. The expression of PAI-1 mRNA in peritoneal mesothelial cells and activities of PAI in the supernatants were enhanced by 11.2 mmol/L glucose, gentamicin and cefazolin at 12 hr. By 24 hr, the activity of PAI-1 also increased in the supernatants with 11.2 mmol/L glucose. The expression of PAI-1 mRNA and production of PAI activities by the peritoneal mesothelial cells were increased by gentamicin, and the TGF-beta mRNA increased in the peritoneal mesothelial cells was induced by 11.2 mmol/L glucose, gentamicin and cefazolin. The results suggested that 11.2 mmol/L glucose, gentamicin and cefazolin may increase the expressions or productions of PAI and TGF-beta in peritoneal mesothelial cells. So by perosmotic glucose, cefazolin and gentamicin promote the peritoneal fibrosis in patients with CAPD.

Animals↗

Compatibility and stability of linezolid injection admixed with three cephalosporin antibiotics.

OBJECTIVE: To evaluate the physical compatibility and chemical stability of linezolid (Zyvox-Pharmacia) 200 mg/100 mL admixed with cefazolin sodium 1 gram, ceftazidime 2 grams, and ceftriaxone sodium 1 gram for 7 days at 4 degrees C and 23 degrees C. DESIGN: Controlled experimental trial. SETTING: Laboratory. INTERVENTIONS: The test samples were prepared by adding the required amount of the cephalosporin antibiotic to bags of linezolid injection 200 mg/100 mL. MAIN OUTCOME MEASURES: Physical stability and chemical stability based on drug concentrations initially and after 1, 3, 5, and 7 days of storage at 4 degrees C and 23 degrees C protected from light. RESULTS: All of the linezolid admixtures with cephalosporins were clear when viewed in normal fluorescent room light and with a Tyndall beam. Measured turbidity and particulate content were low and exhibited little change. The cefazolin sodium-containing samples were colorless throughout the study. The admixtures with ceftazidime and ceftriaxone sodium had a slight yellow tinge initially, and the room temperature samples became a frank yellow color after 5 days. The refrigerated samples did not change color. High-performance liquid chromatography analysis found little or no loss of linezolid in any sample stored at either temperature throughout the study. Cefazolin sodium and ceftazidime in the linezolid admixtures at 4 degrees C remained stable for 7 days, but at 23 degrees C cefazolin sodium was stable for 3 days and ceftazidime for only 24 hours before cephalosporin decomposition exceeded 10%. Ceftriaxone sodium was less stable in the admixtures; 10% loss occurred in 3 days at 4 degrees C and more than 20% loss occurred in 24 hours at 23 degrees C. CONCLUSION: Admixtures of linezolid 200 mg/100 mL with cefazolin sodium 1 gram and ceftazidime 2 grams were physically compatible and chemically stable for at least 7 days stored at 4 degrees C protected from light and for 3 days and 1 day, respectively, at 23 degrees C protected from light. Admixtures of linezolid with ceftriaxone sodium 1 gram exhibited a rapid rate of cephalosporin loss at 23 degrees C, which precludes admixture of the two drugs.

Acetamides↗

[Vascular graft infection by Staphylococcus epidermidis: efficacy of various perioperative prophylaxis protocols in an animal model].

A rat model was used to investigate the efficacy of levofloxacin, cefazolin and teicoplanin in the prevention of vascular prosthetic graft infection. Graft infections were established in the subcutaneous tissue of 300 male Wistar rats by implantation of Dacron prostheses followed by topical inoculation with methicillin-susceptible and methicillin-resistant S. epidermidis. The study included a group without contamination, two contaminated groups without prophylaxis, two contaminated groups with intraperitoneal levofloxacin prophylaxis (10 mg/kg), two contaminated groups with intraperitoneal cefazolin prophylaxis (30 mg/kg), two contaminated groups with intraperitoneal teicoplanin prophylaxis (10 mg/kg) and six contaminated groups with rifampin-soaked graft and intraperitoneal levofloxacin, cefazolin or te- icoplanin prophylaxis. The grafts were removed after 7 days and evaluated by quantitative culture. The efficacy of levofloxacin against the methicillin- susceptible strain did not differ from that of cefazolin or teicoplanin. Levofloxacin showed slight less efficacy than teicoplanin against the methicillin-resistant strain. The levofloxacin-rifampin combination proved to be similarly effective to the rifampin-teicoplanin combination and more effective than the rifampin-cefazolin combination against both strains. The rifampin-levofloxacin combination may be useful for the prevention of late-appearing vascular graft infections caused by S. epidermidis because it takes advantage of the good anti-staphylococcal activity of both drugs.

Animals↗

[Chemotherapy of purulent meningitis in children (author's transl)].

Purulent meningitis in patients admitted to the pediatric department of Kyoto University Hospital and affiliated institutions from 1951 through 1973 were studied with emphasis on the kinds of the causative organisms and the susceptibility of these organisms to antibiotics. The findings in this study have served to help select antibiotics most likely to be effective against this disease. The overall incidence of purulent meningitis was 0.68%. This figure decreased little throughout the period. As for the frequency of causative organisms, Neisseria meningitidis led the list, and Diplococcus pneumoniae ranked just behind. Haemophilus influenzae was rare. The frequency of N. meningitidis, however, decreased sharply in spite of the essentially unchanged overall incidence of this disease. The probable reason for the poor prognosis of this disease in spite of the remarkable strides in chemotherapy is the decreased frequency of N. meningitidis and the inversely increased organisms that are resistant to usual chemotherapy. The therapeutic effectiveness of cefazolin against this disease was studied in 15 children including eight newborns and four infants. The daily per kg bodyweight dose was 50 mg or less in four, 50 approximately 100 mg in five, and more than 100 mg in the remaining six. The route of administration was either intramuscular or intravenous. No deaths occurred. The rate of effectiveness was as high as 80%. Residual symptoms were recorded in six and, in as many as five of them, the cause was a-tributable to the delayed detection of the disease. Neither side effects nor aberrent laboratory findings attributable to large doses of cefazolin were recorded. Diffusibility of cefazolin into the CSF was studied in nine subjects. The CSF concentration of this antibiotic was shown to be somewhat lower than that of ampicillin or cephaloridine and to account on an average for 13% of the mean peak serum level. This relatively low diffusibility will be offset by its high serum concentration and safe large-dose therapy. These findings have clearly shown that the therapeutic effectiveness of cefazolin is as high as that of ampicillin, and that this excellent effectiveness holds true even when the causative organism happens to be Escherichia coli, Klebsiella, etc. that are resistant to ampicillin. The authors have furthermore scrutinized much literature on the frequency of the causative organisms, emergence of resistant strains, and the diffusibility of antibiotics into the CSF, and arrived at the conclusion that cefazolin is a promising antibiotic of choice for the treatment of purulent meningitis in newborn. The daily dose is preferably 150 mg/kg or more given in three divided intravenous doses. Meanwhile ampicillin proved to be useful as the antibiotic of choice for the treatment of purulent meningitis in infants and children.

Age Factors↗

Impaired antibiotic entry into lung tissue following acid injury.

The purpose of this study was to compare the lung tissue burden of intravenous (i.v.) and intrabronchial (i.b.) cefazolin, using a standardized hydrochloric acid injury to the lungs. Ten mongrel dogs were anesthetized with pentobarbital and artificially ventilated. Following administration of cefazolin i.v. (N = 5) or i.b. (N = 5), lung biopsies were obtained at 6 hourly intervals. Simultaneous serum levels were also determined. The effective time (Teff) was defined as the period during which all serum and lung specimens demonstrated antibiotic activity exceeding 8 mcg/gm. These levels should provide comprehensive coverage of common lung and wound pathogens that are sensitive to cefazolin. Teff for the i.v. group was 1 hour, while aerosolized cefazolin never produced lung levels exceeding 8 mcg/gm. Thus, these findings suggest an explanation for cefazolin failure in gram negative pneumonia.

Aerosols↗

[Effects of plasma albumin on theophylline concentration in lung tissue].

To study the relationship between plasma and lung tissue theophylline concentrations, we changed the number of binding sites for theophylline on serum albumin. Cefazoline, which competes with theophylline for those binding sites, was given to rats, and free theophylline was separated by ultrafiltration. The dose of cefazoline was directly related to the percentage of free theophylline and was inversely related to the plasma total theophylline concentration. The plasma free theophylline concentration, however, was unchanged at the lower doses of cefazoline and was low only at the highest dose. The concentration of theophylline in lung tissue was inversely related to the dose of cefazoline. The concentration of 1, 3-dimethyluric acid, a major metabolite of theophylline, was also inversely related to the dose of cefazoline, which suggests that the metabolic rate of theophylline did not increase. Excretion of theophylline via the urine might be accelerated by its diuretic action. We conclude that when the binding of theophylline to plasma proteins is altered in rats, the concentration of free theophylline in plasma does not reflect the concentration of theophylline in lung tissue. Instead, the total theophylline concentration in plasma can be used as an index of the concentration in lung tissue.

Animals↗

Studies on the duration of antibiotic administration for surgical prophylaxis.

Patients undergoing 801 elective, clean-contaminated operations were assigned to one of the three following antibiotic regimens: 1) 1 g of cefazolin preoperatively, 2) 1 g of cefazolin preoperatively and another 1-g dose 3 hours later, and 3) 1 g of cefotetan preoperatively. These antibiotic regimens resulted in similar wound infection rates for procedures completed within 3 hours. When the procedure lasted more than 3 hours, the 6.1 per cent infection rate noted when a single dose of cefazolin was given proved significantly greater than the 1.3 per cent infection rates associated with the use of two doses of cefazolin or a single dose of the longer acting antibiotic, cefotetan (P < 0.01). Another series of 768 patients undergoing biliary and gastrointestinal tract operations were assigned to one of two antibiotic regimens: 1) a preoperative dose of 1 g of cefazolin and another 1-g dose 3 hours later if still in the operating room; 2) same as (1), plus 1-g doses every 8 hours for 24 hours. The longer period of antibiotic administration failed to improve the wound infection rate compared to the use of perioperative coverage only. These studies suggest that a single dose of preoperative antibiotic is sufficient for surgical prophylaxis when the operation is completed within 3 hours. Antibiotic coverage must extend for the duration of longer operations. A second dose of antibiotic or a single preoperative dose of an extended half-life antibiotic are equally effective. There is no value to administering antibiotics after the operation has been completed.

Antibiotic Prophylaxis↗