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Infections with gram-negative bacilli in a cardiac surgery intensive care unit: the relative role of enterobacter.

A 7-month prospective survey for cefazolin-resistant Gram-negative bacilli in cardiac surgery patients, receiving cefazolin prophylaxis, showed that 58 (67%) of 87 were colonized with enterobacter, 37 (64%) with citrobacter, 33 (57%) with Pseudomonas aeruginosa, and seven (2%) with Serratia marcescens. About 50% of colonization occurred before cefazolin prophylaxis and was present on admission to the intensive care unit. Typing of strains showed that horizontal transmission accounted for at most 14% of carriage. Cefazolin prophylaxis (and high gastric pH) were associated with increased levels of postoperative colonization, most notably for enterobacter. About 25% of colonization with enterobacter, pseudomonas, and serratia was followed by clinical infection. Enterobacter cloacae was the most common pathogen and pneumonia the most common infection. Infections contributed to eight of 11 deaths; four of the eight involved enterobacter. Potential control measures include eliminating endogenous Gram-negative flora by gut decontamination or at least stemming the increase in level of colonization that occurred after surgery.

Adult↗

Activity of cephalosporins against coagulase-negative staphylococci.

Staphylococcus epidermidis has become an increasingly important pathogen as the cause of serious postoperative infection after heart and orthopedic surgery. We studied the susceptibilities of 80 blood, sternotomy, and hip isolates to vancomycin, cefazolin, cefuroxime, oxacillin, erythromycin, ciprofloxacin, and ofloxacin. The MIC90 of methicillin-susceptible isolates was 4 micrograms/ml for cefazolin and cefamandole, 8 micrograms/ml for cefuroxime, and 4 micrograms/ml for vancomycin. At 48 hr the MIC90 rose to 32 micrograms/ml for cefazolin and greater than 128 micrograms/ml for cefuroxime, and remained at 4 micrograms/ml for cefamandole and vancomycin. The MIC90 of methicillin-resistant isolates at 48 hr was 16 micrograms/ml cefamandole, 64 micrograms/ml cefazolin, greater than 128 micrograms/ml cefuroxime, and 4 micrograms/ml vancomycin. Ciprofloxacin and ofloxacin inhibited the majority of isolates at 1 microgram/ml, and vancomycin at 4 micrograms/ml. The new peptolide, daptomycin, also inhibited S. epidermidis at less than or equal to 1 microgram/ml.

Cefamandole↗

Perioperative antibiotic prophylaxis in the gastric bypass patient: do we achieve therapeutic levels?

BACKGROUND: Perioperative surgical antibiotic prophylaxis requires that therapeutically effective drug concentrations be present in the tissues. METHODS: Patients undergoing Roux-en-Y gastric bypass for morbid obesity were given 2 g cefazolin preoperatively, followed by a second dose at 3 hours. Thirty-eight patients were each assigned to 1 of 3 body mass index (BMI) groups: (A) BMI=40-49 (N = 17); (B) BMI=50-59 (N=11); (C) BMI > or= 60 (N=10). Multiple timed serum (baseline; incision, 15, 30, 60 minutes; prior to second prophylactic dose; and closure) and tissue (skin, subcutaneous fat, and omentum) specimens were collected and cefazolin concentration analyzed by microbiological assay. RESULTS: No significant difference was observed in intraoperative fluid replacement or blood loss among BMI groups. Serum antimicrobial concentrations exceeded resistance breakpoint (32 microg/mL) in 73%, 68%, and 52% of BMI groups A, B, and C, respectively. No significant difference in cefazolin concentration was observed in mean incisional skin and closure tissue specimens in groups A, B, and C. A significant decrease in cefazolin concentration was noted in closure adipose (p=.04), initial (p=.03) and closure omentum (p=.05) tissues in groups B and C compared with A. Over 90% of serum samples exhibited therapeutic concentrations covering 53.8% of gram-positive and 78.6% of gram-negative surgical pathogens. However, therapeutic tissue levels were achieved in only 48.1%, 28.6%, and 10.2% of groups A, B, and C, respectively. CONCLUSIONS: Pharmacokinetic analysis suggests that present dosing strategies may fail to provide adequate perioperative prophylaxis in gastric bypass patients.

Adult↗

An in vitro study of the potency and stability of fortified ophthalmic antibiotic preparations.

We studied the potency of fortified ophthalmic antibiotic preparations of cefazolin sodium (50 mg/ml) and tobramycin sulfate (15 mg/ml), as measured by the minimum inhibitory concentration, against Streptococcus pneumoniae and Pseudomonas aeruginosa, respectively. We also examined absorbance spectra, pH, and the effect of storage temperature on these fortified solutions to determine their stability over a four-week period. Cefazolin and tobramycin maintained a constant potency throughout the experiment. There was no difference in potency if the fortified solutions were stored at 4 C or 24 C. Cefazolin stored at 24 C exhibited changes in both its absorbance spectra and pH after seven days. Cefazolin stored at 4 C and tobramycin stored at 24 C and 4 C remained stable throughout the four-week period.

Anti-Bacterial Agents↗

In vitro susceptibility of Yersinia kristensenii strains to beta-lactam antibiotics.

The beta-lactam antibiotic susceptibility and beta-lactamase activity of 22 Yersinia kristensenii strains were determined in order to compare these properties with those reported for Y. enterocolitica. Carbenicillin, cephaloridine, cefoxitin and cefotaxime were the most active antimicrobial agents tested against Y. kristensenii. All strains were resistant to penicillin G, cephalothin, cephapirin and cephalexin. On the other hand, ampicillin and cefazolin activity could be considerated as intermediate. The influence of incubation temperature was also evaluated. All Y. kristensenii strains were more resistant at 22 degrees C than at 37 degrees C to beta-lactam antibiotics. Susceptibility to cefazolin was not affected by the incubation temperature. All Y. kristensenii strains produce beta-lactamase. The substrate profile of this enzyme is that of a cephalosporinase: its activity was highest on cephalothin, cephapirin, cephaloridine and cefazolin, while hydrolysis of ampicillin and carbenicillin was not detected. beta-Lactamase-resistant cefoxitin and cefotaxime were not hydrolysed. A correlation between beta-lactam antibiotic susceptibility and the hydrolysis rate of these antibiotics by beta-lactamase was observed, except for cephaloridine and cefazolin; these antibiotics were very good beta-lactamase substrates, but their MIC values were low.

Ampicillin↗

Expression levels of renal organic anion transporters (OATs) and their correlation with anionic drug excretion in patients with renal diseases.

PURPOSE: Because the urinary excretion of drugs is often decreased in renal diseases, dosage regimens are adjusted to avoid adverse drug reactions. The aim of present study was to clarify the alteration in the levels of renal drug transporters and their correlation with the urinary drug excretion in renal diseases patients. METHODS: We quantified the mRNA levels of human organic anion transporters (hOATs) by real-time polymerase chain reaction and examined the excretion of the anionic drug, cefazolin, in renal disease patients. Moreover, transport of cefazolin by hOAT1 and hOAT3 were examined using HEK293 transfectants. RESULTS: Among four hOATs, the level of hOAT1 mRNA was significantly lower in the kidney of patients with renal diseases than in the normal controls. The elimination constant of cefazolin showed a significant correlation with the values of phenolsulfonphthalein test and mRNA levels of hOAT3. The uptake study using HEK293 transfectants revealed that cefazolin and phenolsulfonphthalein were transported by hOAT3. CONCLUSIONS: These results suggest that hOAT3 plays an important role for anionic drug secretion in patients with renal diseases and that the expression levels of drug transporters may be related to the alteration of renal drug secretion.

Adult↗

Role of preoperative antibiotic prophylaxis in preventing postoperative peritonitis in newly placed peritoneal dialysis catheters.

The role of vancomycin and other antibiotics in the treatment of acute peritonitis in peritoneal dialysis (PD) patients is well established. However, the role of preoperative vancomycin or cephalosporins in preventing early infection in newly placed PD catheters remains controversial. We performed a prospective randomized study to examine the role of vancomycin or cefazolin prophylaxis in decreasing the incidence of postoperative peritonitis. Over a 6-year period, 221 patients undergoing 254 permanent peritoneal catheter placement procedures were randomized into three groups. Group I patients (86 procedures) were administered a single intravenous (IV) dose of vancomycin, 1,000 mg, 12 hours before peritoneal catheter placement procedures, whereas group II patients (85 procedures) were administered a single IV dose of cefazolin, 1,000 mg, 3 hours before the procedure. Group III patients (83 procedures) were not administered antibiotics preoperatively for at least 1 week before the procedure. Patients were monitored for peritonitis in the following 14 days. Peritonitis developed in 1 patient (1%) in group I (vancomycin group) and 6 patients (7%) in group II (cefazolin group) compared with 10 patients (12%) in group III (control group); P = 0.02. We conclude that the use of preoperative single-dose IV vancomycin prophylaxis for permanent PD catheter placement reduces the risk for postoperative peritonitis. Single-dose vancomycin is superior to single-dose cefazolin in reducing the risk for postoperative peritonitis. Absence of prophylaxis is associated with a high risk for developing postoperative peritonitis.

Adolescent↗

Treatment of urinary tract infections with cefotaxime: noncomparative and prospective comparative trials.

Three studies evaluated the efficacy of cefotaxime for the treatment of urinary tract infections. An open, multicenter, noncomparative trial included 477 patients who received a usual dose of 2 g of intravenous or intramuscular cefotaxime daily for five to 10 days. The maximal daily dosage in severe cases was 12 g. Pathogens included Escherichia coli and species of Citrobacter, Pseudomonas, Klebsiella, Enterobacter, Serratia, Morganella, Providencia, and Proteus. Of all the causative organisms, 83.6% were eradicated in the 271 patients who could be evaluated. The other two studies were prospective, randomized comparisons of cefotaxime (392 patients) with cefazolin (250 patients) for the treatment of urinary tract infections caused by microorganisms susceptible to both antibiotics. The treatment schedule was the same as that in the first study. Results of these two prospective studies were pooled. Cefotaxime eradicated 90% of all pathogens, and cefazolin eradicated 72%. Cefotaxime was significantly more effective (P less than 0.01) than cefazolin in eradicating E. coli and Proteus mirabilis. A satisfactory clinical response was obtained in 98.1% of patients given cefotaxime and in 87.6% of those given cefazolin (P less than 0.01).

Adolescent↗

Alteration of staphylococcal flora in cardiac surgery patients receiving antibiotic prophylaxis.

The changes in staphylococcal flora induced by antibiotic prophylaxis with rifampin and nafcillin in combination among patients undergoing cardiac valve surgery were compared to those in patients undergoing coronary artery bypass surgery concurrently, who received only cefazolin. Rifampin-nafcillin prophylaxis eradicated carriage of Staphylococcus aureus at a significantly higher rate than did cefazolin (eradicated carriage of 89% vs. 48%, respectively; P less than 0.01); however, by the seventh postoperative day, 75% of the patients receiving rifampin and nafcillin had rifampin-resistant, coagulase-negative staphylococcal perianal floras, compared to 19% of those who received cefazolin (P less than 0.001). Patients receiving rifampin-nafcillin were colonized as frequently (66%) with coagulase-negative staphylococci resistant to gentamicin and methicillin as were those receiving cefazolin (68%). Patients in the coronary intensive care unit who received no antibiotics were infrequently colonized with either rifampin-resistant (none) or gentamicin- and methicillin-resistant (11%) staphylococci. Antibiotic prophylaxis may, therefore, be an important factor in perpetuating the hospital reservoir for antibiotic-resistant, coagulase-negative staphylococci.

Anti-Bacterial Agents↗

The effect of prophylactic antibiotics on iatrogenic intervertebral disc infections. a rabbit model.

STUDY DESIGN: A rabbit model was used to test the efficacy of two commonly used prophylactic antibiotics, cefazolin and vancomycin, in preventing iatrogenically introduced Staphylococcus aureus intervertebral disc infections. OBJECTIVE: This study was performed to assess the efficacy of two prophylactic antibiotics in preventing iatrogenically introduced Staphylococcus aureus intervertebral disc infections. SUMMARY OF BACKGROUND DATA: Previous studies have had conflicting results regarding the penetration of antibiotics into the nucleus pulposus and their ability to eradicate infection. METHODS: In this study, 40 adult New Zealand White rabbits underwent inoculation of 10(1) or 10(3) Staphylococcus aureus/ml into 3-6 lumbar intervertebral discs under direct visualization. Either no antibiotics (control groups) or various preoperative and postoperative dosing schedules of cefazolin or vancomycin were given intravenously. Five days after surgery, the discs were harvested and cultured. RESULTS: All 40 discs inoculated in the control groups became infected. None of the 35 discs inoculated in the cefazolin groups became infected. Infection developed in 23 of 107 discs inoculated in the vancomycin groups. Most notable of these were 17 of 17 positive cultures in animals given vancomycin 8 hours preoperatively only. CONCLUSIONS: Based on these results, it was concluded that intravenous cefazolin or vancomycin given within 1 hour before surgery can effectively prevent postoperative discitis. No advantage was found with additional postoperative antibiotics.

Animals↗

The role of prophylactic antibiotics in spinal instrumentation. A rabbit model.

STUDY DESIGN: A rabbit model was used to test the efficacy of cefazolin administered in various therapeutic regimens in preventing iatrogenic Staphylococcus aureus infections during spinal instrumentation. OBJECTIVE: To assess the efficacy of various prophylactic therapeutic regimens of cefazolin in preventing iatrogenic S. aureus infections during spinal instrumentation. SUMMARY OF BACKGROUND DATA: Previous studies have not dealt specifically with the occurrence of iatrogenic S. aureus infections during spinal instrumentation in a prospective fashion. METHODS: Twenty New Zealand White rabbits underwent a posterior approach to the lumbar spine. Fifteen of the animals then had double-braided 26-gauge surgical wire placed around bilateral L3-L4 and L4-L5 facet joints. A standardized volume of a 103 S. aureus/mL of solution was then inoculated onto the fusion-hardware site in all rabbits. The rabbits were divided into four groups receiving various antibiotic dose regimens. Five days after surgery, the animals were killed, and cultures were obtained. RESULTS: All of the rabbits receiving no antibiotic had fusion sites infected with S. aureus. None of the animals who received prophylactic cefazolin produced cultures that grew S. aureus. A specimen from one fusion site cultured Staphylococcus epidermidis, which is not sensitive to cefazolin. Analysis of these data using Fisher's exact test resulted in a P value of 0.008 when results in antibiotic groups were compared with those in a group receiving no antibiotics and a P value of 0.0003 when all groups were compared. CONCLUSIONS: This model was valid and reproducible for the study of spinal instrumentation and infection. In addition, the data support the efficacy and use of prophylactic intravenous antibiotics in preventing infection in spinal instrumentation and fusion surgery.

Animals↗

Penetration of antibiotics into the surgical wound in a canine model.

The dose and timing of antimicrobial agents given for surgical wound prophylaxis should be based on the concentration-time profile of the drug in tissue at the site of contamination. However, concentrations of antimicrobial agents in surgical wounds are difficult to determine accurately. Since a surgical wound is a unique extravascular compartment with increased vascular permeability and a high surface area/volume ratio, antibiotic concentrations in sera and surgical wounds should be similar. To test this hypothesis, the pharmacokinetics of single intravenous doses of cefazolin (40 mg/kg) and gentamicin (4 mg/kg) in sera and surgical wounds in a clinically relevant surgical model using dogs were compared. Drug concentrations were determined in interstitial fluid in muscle biopsies taken randomly from wound surfaces and serial wound fluid samples collected after the incisions were closed. Protein binding of cefazolin and gentamicin in sera and wound fluids was low (less than or equal to 29 +/- 9%) in this canine model. Cefazolin and gentamicin equilibrated rapidly (less than or equal to 30 min) between serum and the surgical wound, and concentrations in the two sites declined in parallel. Values for the area under the concentration-time curve, mean residence time, and terminal half-life in serum and the surgical site for each drug were similar. Cefazolin concentrations in serum underestimated the time during which concentrations in surgical wounds exceeded the susceptibility breakpoint MIC for important pathogens by an average of 58 min (range, 26 to 109 min; P = 0.036); for gentamicin, the underestimation averaged 30 min (range, 10 to 60 min; P = 0.036). These data support the concept that the concentration-time profiles of antimicrobial agents in serum may prove valuable clinically as guides to determining the and timing of antibiotic administration necessary for effective antimicrobial prophylaxis in surgery. Further studies are needed to determine the surgical wound pharmacokinetics of highly protein-bound antibodies.

Animals↗

Efficacies of various antimicrobial agents in treatment of Staphylococcus aureus abscesses and correlation with in vitro tests of antimicrobial activity and neutrophil killing.

A rabbit perforated-capsule model was utilized to study antimicrobial efficacy in treating 2-week-old Staphylococcus aureus abscesses. Animals received either ciprofloxacin (30 mg/kg), cefazolin (100 mg/kg), or ciprofloxacin (30 mg/kg) plus rifampin (20 mg/kg) every 8 h for 8 days or no antibiotic. Antibiotic levels within the abscess exceeded the MIC for the test organism. At the end of treatment, ciprofloxacin was no more effective than the control, animals receiving cefazolin had a mean log10 fall of 2.41 CFU/ml, and animals receiving ciprofloxacin plus rifampin had a mean log10 reduction of 5.06 CFU/ml (P = less than 0.01). Six days after completion of therapy, all abscesses in animals receiving ciprofloxacin plus rifampin were culture negative. Surviving organisms in animals receiving ciprofloxacin or rifampin did not develop resistance to the treatment antibiotics. In vitro time-kill curves performed with logarithmic- and stationary-phase organisms in broth, serum, and abscess fluid supernatants did not correlate with the in vivo results. Neutrophil killing studies of S. aureus pretreated with antibiotics revealed greater killing of organisms pretreated with ciprofloxacin plus rifampin than of those pretreated with cefazolin or ciprofloxacin alone. In conclusion, ciprofloxacin plus rifampin was effective therapy in this staphylococcal abscess model, compared with the moderate efficacy of cefazolin and no effect observed with ciprofloxacin alone. Enhanced neutrophil killing of S. aureus pretreated with antibiotics may be an important mechanism by which bacteria are killed in suppurative infections.

Abscess↗

Association of borderline oxacillin-susceptible strains of Staphylococcus aureus with surgical wound infections.

Staphylococcus aureus isolates which produce type A staphylococcal beta-lactamase have been associated with wound infections complicating the use of cefazolin prophylaxis in surgery. To further evaluate this finding, 215 wound isolates from 14 cities in the United States were characterized by antimicrobial susceptibility and beta-lactamase type and correlated with the preoperative prophylactic regimen. Borderline-susceptible S. aureus isolates of phage group 5 (BSSA-5), which produce large amounts of type A beta-lactamase and exhibit borderline susceptibility to oxacillin, comprised a greater percentage of the 120 wound isolates associated with cefazolin prophylaxis than they did of the 95 isolates associated with other prophylactic regimens (25% versus 12.6%, respectively; P < 0.05). In contrast, methicillin-resistant S. aureus isolates were distributed evenly between the two groups (8.3% versus 11.6%, respectively). In vitro assays demonstrated that cefazolin was hydrolyzed faster by BSSA-5 strains than by other beta-lactamase-producing, methicillin-susceptible strains (1.54 versus 0.50 microg/min/10(8) CFU, respectively; P < 0.0001). These data demonstrate that BSSA-5 strains are a distinct subpopulation of methicillin-susceptible S. aureus which frequently cause deep surgical wound infections. Cefazolin use in prophylaxis is a risk factor for BSSA-5 infection.

Cefazolin↗

A randomized prospective study of oral versus intravenous antibiotic prophylaxis against postoperative infection after sagittal split ramus osteotomy of the mandible.

BACKGROUND: We investigated whether oral levofloxacin was as effective as intravenous cefazolin sodium for preventing postoperative infections in patients undergoing sagittal split ramus osteotomy of the mandible. METHODS: Forty-four patients were randomized to treatment with levofloxacin or cefazolin sodium. Levofloxacin (100 mg t.d.s.) was administered orally, and cefazolin sodium (1 g b.i.d.) by intravenous infusion. Both drugs were given until 5 days postoperatively. The concentrations of levofloxacin in the mandibular bone marrow and serum were measured. RESULTS: The mean levofloxacin concentration 4 h and 53.7 min after administration was 1.086 microg/ml in serum and 1.328 microg/ml in the mandibular bone marrow. The efficacy rate of levofloxacin was 95% and that of cefazolin sodium was 85.7%, with no significant difference between the two drugs (p = 0.322). CONCLUSION: Oral administration of levofloxacin is a simple, cost-effective and safe alternative to intravenous antibiotic prophylaxis after mandibular surgery.

Administration, Oral↗

In vitro and in vivo comparative evaluations of injectable cephalosporin derivatives and ampicillin.

The in vitro and in vivo activity of the 5 injectable cephalosporins, cefazolin, cephaloridine, cephalothin, cephapirin, cephacetrile, and ampicillin was compared. No gram-positive organisms resistant to any of the cephalosporin derivatives were encountered. The MIC of ampicillin for gram-positive organisms was distributed over a wide range. The antibacterial activity of cefazolin, cephaloridine and ampicillin was high against gram-negative organisms. Ampicillin was potently effective especially against P. mirabilis and cefazolin especially against K. pneumoniae. The protecting effect of the 5 cephalosporins on experimental infections in mice was compared. The effect of cefazolin and cephaloridine was more marked than that of the others. These results may be explained by the fact that the other 3 cephalospoirins are rapidly metabolized in the living body.

Ampicillin↗

Wound prophylaxis with metronidazole in head and neck surgical oncology.

Anaerobic organisms are thought to be an important source of wound infection in head and neck oncologic surgery. Antibiotic prophylaxis consisting of agents specific for anaerobes combined with broad-spectrum agents that provide coverage for other well-recognized pathogens should be an effective combination regimen for this group of patients. We conducted a prospective, randomized study comparing the efficacy of prophylaxis using combination of metronidazole and cefazolin-designated group A, to prophylaxis using cefazolin alone-group B, for patients undergoing oncologic procedures of the head and neck. The rate of wound infection in the cefazolin-metronidazole group (158 patients) was 9.5%, compared with 18.6% in the cefazolin group (172 patients) (p = 0.03). Patients undergoing clean procedures had a 4.9% infection rate overall, compared with 17.9% for clean-contaminated procedures, and 33.3% for contaminated procedures. The average length of hospitalization was 20.7 days for patients who developed infections, compared with 8.9 days for patients without infection. Anaerobic organisms were cultured in 12 of 26 patients, ten of whom did not receive metronidazole. The lower rate of wound infection among patients who received metronidazole suggests that anaerobic organisms are an important source of wound infection in head and neck oncologic surgery. Chemoprophylaxis for these patients should, therefore, include specific anaerobic coverage in addition to the broad-spectrum agents that cover the more familiar aerobic organisms.

Bacteria, Anaerobic↗

Ciprofloxacin inhibition of experimental fracture healing.

BACKGROUND: Fluoroquinolones, such as ciprofloxacin, have an adverse effect on growing cartilage and endochondral ossification in children. This study was carried out to determine whether ciprofloxacin also has an adverse effect on the healing of experimental fractures. METHODS: Sixty male 300-gram Wistar rats were divided equally into three groups, which received ciprofloxacin, cefazolin, or no treatment for three weeks, beginning seven days after production of a closed, nondisplaced, bilateral femoral fracture. The serum concentrations of the ciprofloxacin and the cefazolin were 2.4 and 146 micrograms per milliliter, respectively. Radiographic, histological, and biomechanical studies were used to evaluate fracture-healing. RESULTS: Radiographs revealed significantly more advanced healing of the control fractures compared with the fractures in the ciprofloxacin-treated group (average stage, 2.1 compared with 1.5, p = 0.01). The cefazolin-treated group was not different from the controls with respect to radiographic healing (average stage, 1.8 compared with 2.1, p = 0.18). Torsional strength-testing of fracture callus exposed to ciprofloxacin revealed a 16 percent decrease in strength compared with the controls (284 compared with 338 newton-millimeters, p = 0.04) and a 49 percent decrease in stiffness (twenty compared with thirty-nine newton-millimeters per degree, p = 0.001). The biomechanical strength in the cefazolin-treated group was not different from that of the controls. Fracture calluses in the animals treated with ciprofloxacin showed abnormalities in cartilage morphology and endochondral bone formation and a significant decrease in the number of chondrocytes compared with the controls (0.77 x 10(4) compared with 1.3 x 10(4) cells per square millimeter, p = 0.004). CONCLUSIONS: These data suggest that experimental fractures exposed to therapeutic concentrations of ciprofloxacin in serum demonstrate diminished healing during the early stages of fracture repair. The administration of ciprofloxacin during early fracture repair may compromise the clinical course of fracture-healing.

Animals↗