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Therapy with hyperbaric oxygen and cefazolin for experimental osteomyelitis due to Staphylococcus aureus in rats.

Hyperbaric oxygen (HBO2) is used as adjunctive therapy for chronic osteomyelitis, yet its efficacy remains controversial. A recently developed rat model for osteomyelitis due to Staphylococcus aureus was used to compare the results of treatment with HBO2, cefazolin, a combination of both, or no treatment. For the induction of tibial osteomyelitis, S. aureus was inoculated into the medullary cavity. Arachidonic acid was used as the sclerosing agent. With that procedure, an infection rate of 96% was attained. For long-term antibiotic treatment, a port system was developed and implanted. Hyperbaric treatment alone reduced the colony-forming units (CFU) from 2.9 x 10(6) to 6.2 x 10(5) x g(-1) of tibial bone. The effect on the infection was more pronounced with antibiotic therapy alone, 10.5 x 10(4) CFU per g of tibial bone were measured. However, changes were most marked using a 4-wk combination therapy consisting of HBO2 and an antibiotic agent. The colony count was 2.7 x 10(3) CFU. Each of the treatment modalities resulted in a significant therapeutic effect. The results not only demonstrated the effectiveness of HBO2 in the treatment of osteomyelitis, but revealed a potential additive effect with the combination of HBO2 and an antibiotic.

Animals↗

[Comparative study of the character of cefazolin pharmacokinetics between Neijiang pig and human].

OBJECTIVE: To study the character of cefazolin (CEZ) pharmacokinetics on Neijiang pig and human. METHODS: The serum concentration of CEZ in 8 normal Chinese adult men, 9 of 8-month male Neijiang pigs and 5 of 4-month male Neijiang pigs were detected by high-performance liquid chromatography (HPLC). RESULTS: The pharmacokinetic parameters suggested that two-compartment model was found in all groups after intramuscular injection of CEZ. In normal men, 8-month pigs and 4-month pigs, the peak time (Tmax) was (58.8 +/- 13.0), (19.7 +/- 9.9) and (18.2 +/- 8.6) min respectively, T1/2 alpha was (42.3 +/- 19.7), (19.0 +/- 7.7) and (9.3 +/- 1.9) min, the peak concentration (Cmax) was (101.6 +/- 14.6), (28.7 +/- 9.0) and (23.5 +/- 4.6) mg/L; Vd was (0.096 +/- 0.016), (0.374 +/- 0.184) and (0.386 +/- 0.211) L/kg; T1/2ka was (22.5 +/- 6.8), (8.6 +/- 4.8) and (10.6 +/- 10.2) min; T1/2 beta was (117.3 +/- 8.6), (84.2 +/- 9.8) and (45.1 +/- 11.5) min; clean rate of plasma Cl was (0.8 +/- 0.1), (6.8 +/- 1.2) and (11.0 +/- 3.0) ml/kg.min; AUC was (21,803 +/- 4,145), (2,407 +/- 443) and (1,636 +/- 685) mg.min/L. CONCLUSION: It could conclude that the Neijiang pigs could eliminate CEZ effectively, but the absorption, distribution and elimination of CEZ in pigs were quicker than that of in human while the absorption from muscle in both pig groups were lower than that in human.

Adult↗

A necropsy case of interstitial nephritis probably related to cefazolin and methenamine.

It is the purpose of this paper to alert the medical community on the potential nephrotoxicity of certain agents among certain patients, especially with some types of renal insufficiency. A young man, who was suffering from apparent renal disturbance, died of massive, post-operative bleeding accompanied by uremia. The uremia occurred within a very rapid clinical course and was related apparently to treatment with methenamine, a ruinary disinfectant, and cefazolin, a cephalosporin derivative. The patient was proved to have a fatal, servere interstitial nephritis based on gross and histological findings of the necropsied kidney, i.e., intense cell infiltration mainly in the interstitum of the cortex, absence of glomerular involvement, and marked softening and enlargement. The present case may suggest how to treat patients suffering from untoward renal ailments with various antibiotics.

Adult↗

[Evaluation of in vitro antimicrobial activity of cefazolin alone and in combination with cefmetazole or flomoxef using agar dilution method and disk diffusion method].

Antimicrobial activities of cefazolin (CEZ) against 251 strains of various clinical isolates obtained during 1989 and 1990 were determined using the Mueller-Hinton agar dilution method at an inoculum level 10(6) CFU/ml. The reliability of the disk susceptility test was also studied using Mueller-Hinton agar and various disks at inoculum levels of 10(3-4) CFU/cm2 in estimating approximate values of MICs. In addition, antimicrobial activities of CEZ and cefmetazole (CMZ) or flomoxef (FMOX) in combination were investigated against methicillin-sensitive and -resistant Staphylococcus aureus (MSSA and MRSA) using the checkerboard agar dilution MIC method and the disk diffusion test either with the disks contained CEZ, CMZ, and FMOX alone, or CEZ, and CMZ or FMOX in combination. In this study, the MICs of CEZ against S. aureus were distributed with the 3 peak values at 0.39 microgram/ml, 3.13 micrograms/ml and > 100 micrograms/ml. MICs against MSSA were 0.39 microgram/ml to 0.78 microgram/ml, whereas those against MRSA were greater than 0.78 microgram/ml. MICs against majority of strains of Enterococcus faecalis were 25 micrograms/ml. Over 90% of strains of Escherichia coli and Klebsiella pneumoniae were inhibited at the level of 3.13 micrograms/ml. About 60% of isolates of indole negative Proteus spp. were inhibited at the levels of less than 3.13 micrograms/ml and 100% at 6.25 micrograms/ml, but MICs against indole positive Proteus spp., Serratia spp. and Pseudomonas aeruginosa were over 100 micrograms/ml. The antimicrobial activities of CEZ against these clinical isolates were not significantly different compared to those reported about 15-20 years ago, except for S. aureus. Highly resistant strains of S. aureus to CEZ were more prevalent in this study. The inhibitory zones obtained with the disk test were compared with MICs. The results of CEZ disk susceptibility test with 30 micrograms disk (Showa) or 10 micrograms disk (prepared in this laboratory) were well correlated with MICs (r = -0.837 and -0.814, respectively), showing the reliavility of the disk method in estimating approximate values of MICs. In the 4 category classification system currently used in Japan, break points in MIC values proposed are () MIC < or = 3 micrograms/ml, (++) > 3-15 micrograms/ml, (+) > 15-60 micrograms/ml, (-) > 60 micrograms/ml. The results obtained with 30 micrograms disks showed false positive in 7.7% and false negative in 6.8% of the samples. The disk results with E. faecalis showed a higher ratio of false positive results.(ABSTRACT TRUNCATED AT 400 WORDS)

Bacteria↗

Photo recall effect in association with cefazolin.

Patients in remission from local dermatitis secondary to external beam radiation treatments occasionally experience recurrence with systemic chemotherapy, a reaction termed radiation recall. Chemotherapy-induced photo recall from a prior exposure to the sun also has been reported. Rare reports describe photo recall effects from more commonly used medications. We report the case of a patient who developed a photo recall reaction after treatment with cefazolin. Results of the shave biopsy were consistent with a mild phototoxic eruption.

Adult↗

Effect of diabetes on disposition and renal handling of cefazolin in rats.

The effects of early-stage diabetes on disposition and renal handling of cefazolin (CEZ) were investigated in streptozotocin-induced diabetic rats. Significant increase in renal clearance was found in the diabetic rats (88%) and a strong correlation was obtained between renal and systemic clearance; however, there was no change in the volume of distribution. The results suggest that systemic clearance was increased as the result of enhancement of urinary excretion rate. Unbound fraction of CEZ in plasma was also increased by 60% in the diabetic rats and the increase may be due to the increase in glycosylated protein and plasma-free fatty acids. The filtration clearance for free drug in diabetic rats, which was estimated as glomerular filtration rate, was increased by about 1.9-fold compared to the normal rats, but the secretion clearance did not change in the two groups. Since kidney hypertrophy was observed in the diabetic rats, filtration and secretion clearance for free drug were normalized by means of kidney weight. After normalization for kidney weight, the two parameters were significantly reduced, indicating that the true kidney functions were impaired under the diabetic state. The parameters for CEZ secretion, maximum velocity and Michaelis-Menten constant, were also reduced in diabetic rats, suggesting that proximal tubule cell functions for secretion were altered in the diabetic rats. These results suggest that systemic and renal clearance was apparently increased in early-stage diabetes, whereas true kidney functions were impaired.

Animals↗

[Susceptibilities of uropathogenic bacteria to ampicillin, cefazolin, cefmetazole and gentamicin. Nine-year survey of changing patterns of susceptibilities].

We analyzed antibiotic susceptibilities of urinary isolates of Escherichia coli, Klebsiella spp., Proteus mirabilis, and Indole (+) Proteus group to ampicillin (ABPC), cefazolin (CEZ), cefmetazole (CMZ) and gentamicin (GM) in 69 laboratories in 1988 and also studied changing patterns of susceptibilities from 1980 to 1988. Minimal inhibitory concentrations were determined using the agar dilution method (MUELLER-HINTON agar, BBL) with inoculation of 10(6) cfu/ml of bacteria. Ninety to 99% of the strains of E. coli, Klebsiella spp. and P. mirabilis were inhibited at a concentration of 6.25 micrograms/ml of CEZ and CMZ and of 1.56 micrograms/ml of GM. Approximately 80% of the strains of Indole (+) Proteus group were inhibited at concentrations of 6.25 micrograms/ml of CMZ and of 1.56 micrograms/ml of GM. However, resistance to ABPC and CEZ was high, with 83% and 81% of the strains being not inhibited at a concentration of 50 micrograms/ml of ABPC and CEZ, respectively. No significant changes in susceptibilities of the 4 bacteria to the above 4 antibiotics were observed over the 9 year period. No increase was found in the incidence of the resistant strains of the 4 bacteria to CMZ and GM, nor of E. coli and Klebsiella spp. to CEZ.

Ampicillin↗

[Ceftriaxone or combined cefazolin-gentamicin for complicated urinary tract infections].

40 seriously ill patients with complicated urinary tract infections were randomly assigned to receive either a single daily dose of ceftriaxone or combined therapy with cefazolin and gentamicin administered every 8 hours. The groups were of equal size, similar in age (both averaged 75 years) and the sex ratio was about 1:1 in each group. 32.5% had proven bacteremia and the overall mortality was 17.5%. Both regimens were similarly effective in terms of mortality, duration of fever (3.0-3.1 days), and sterilization of the urine prior to discharge from hospital. However, the single daily dose of ceftriaxone was much more convenient to administer.

Aged↗

Photo recall-like phenomenon following the use of cefazolin and gentamicin sulfate.

A twenty-one-year-old woman being treated as an inpatient for a urinary tract infection with cefazolin and gentamicin showed a photodistributed eruption five days into her hospitalization. Photo recall phenomena are well known to occur in patients receiving chemotherapeutic agents after sustaining prior skin damage from radiation therapy or the sun. Similar reports with more commonly used agents are sparse. We report a photo recall-like phenomenon comprised of a similar entity with a different reaction pattern. After reviewing the literature on photo recall phenomena, we compare and contrast our case with those previously reported.

Adult↗

[Prophylactic antibiotherapy in biliary surgery, cefazolin versus cefoperazone. Randomized comparative open study in a population at risk for infection].

Sixty patients having to undergo a biliary operation with high risk of infection (Keighley's criterions) received at random either cefazolin (CFZ) or cefoperazone (CFP) as a prophylactic antibiotherapy. Postoperative courses were fairly normal: a peak of temperature on day 5 for one case and a digestive bleeding due to hypoprothrombinemia for another case. No further complication occurred. Patient discharge was two days shorter with cefoperazone and biliary positive cultures were in favour of cefoperazone (21% with CFZ, 11% with CFP) but without statistically significant level. Consequently, this trial should be carried out on a larger scale.

Adolescent↗

[Data averaging in pharmacokinetic analysis: the population pharmacokinetics of cephalothin and cefazolin].

Cephalothin and cefazolin pharmacokinetics was studied in cats after intravenous administration in doses of 20 and 75 mg/kg. The antibiotic serum concentrations were determined microbiologically. It was shown that the antibiotic pharmacokinetics within the above dose ranges was linear. The data on the antibiotic pharmacokinetics were described by bioexponential equations. Various methods for estimating population pharmacokinetic parameters were compared. Two approaches were used in estimating the population parameters: (1) averaging of individual concentrations followed by determining a single set of the parameters (naive pooled data approach) and (2) calculating of the parameters for an individual concentration/time set followed by the parameter averaging (two-stage approach). With the use of every approach the geometric mean of the parameters was calculated along with the arithmetic one. When the two-stage approach was used the population parameters were estimated with two procedures: averaging of the hybrid parameters (macroconstants) and averaging of the microconstants. Estimation of the population parameters as a geometric mean of the individual parameters, proved to be the most preferable approach.

Animals↗

[A study of cephem antibiotics, cefazolin and ceftizoxime, for prophylaxis against infections following obstetric and gynecologic procedures].

Cefazolin (CEZ) and ceftizoxime (CZX) were administered prophylactically to prevent postoperative infections after cesarean section and abdominal simple panhysterectomy, common obstetrical/gynecological procedures. The results were summarized as follows. Total fever indices in cesarean sections for the 2 drug groups were examined and CEZ (n = 8) and CZX (n = 10) indices were found to be 6.0 +/- 3.67 degree hours and 3.6 +/- 1.16 degree hours, respectively. In abdominal simple panhysterectomies, CEZ (n = 11) and CZX (n = 11) indices were 8.15 +/- 5.17 degree hours and 4.26 +/- 2.24 degree hours, respectively. Further, there was a lower daily fever index with CZX than with CEZ in both operation groups. Counts of WBC in both procedure groups were lowest on the 5th postoperative day in the CZX group, so was for the CRP. As for the ESR, the CEZ group was much higher than the CZX group especially in abdominal simple panhysterectomies. Neither subjective/objective side effects nor abnormal laboratory findings were observed in either CEZ or CZX group of patients.

Adult↗

[Treatment of acute perforated appendicitis with intraperitoneal cefazolin].

Until recently intra-abdominal sepsis following surgery for perforated appendicitis has remained a frequent occurrence. In 1975 Fowler reported an incidence of one intra-abdominal abscess in 36 perforated appendicitis treated with a protocol consisting of saline irrigation at surgery, followed by intraperitoneal administration of cephaloridine q. 6 hours for 48 hours. The same antibiotic was then given i.v. for 72 hours. He concluded that this method was an effective way to minimize post-op intra-abdominal abscess, and that the intraperitoneal route was more effective, for this purpose, than systemic administration. More recently, with better knowledge of the role of anaerobes, improved results have also been obtained by adding clindamycin or metronidazole to the antibiotic regimen. A prospective study based on two groups of patients randomly assigned to two protocols was undertaken. The study group consisted of 45 children operated for perforated appendicitis with abscess or generalized peritonitis. These patients were treated with Fowler's protocol. Because it is less nephrotoxic and is active against the same organisms, cefazolin was used instead of cephaloridine. The control group consisted of 43 patients, also operated for perforated appendicitis, treated with saline irrigation at surgery, with either i.v. gentamycin or tobramycin and clindamycin or metronidazole for an average of 7.8 +/- 3.1 days. Both groups were fairly well matched in terms of age, sex, severity of disease, and bacterial flora. They showed an identical 6% post-op intra-abdominal sepsis rate. Days before afebrile, days under gastric suction, complications and average hospital stay were comparable in both groups. The wound infection rate was 20% in the study group and 9% in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Abscess↗

[Pharmacokinetics of cefazolin during hemosorption and hemodialysis].

The influence of hemosorption and hemodialysis on the pharmacokinetics of cefazolin was studied in 20 patients with chronic and acute renal insufficiency. The integral mean value of the antibiotic extraction coefficient in hemosorption was approximately 2 times higher than that in hemodialysis. In the first case the value of this parameter systematically lowered with time (the constant of the process rate amounted to 0.89 h-1), while in the second case it was constant.

Cefazolin↗

A comparative trial of cefazolin and moxalactam as prophylaxis for preventing infection after abdominal hysterectomy.

In a randomized, double-blind clinical trial, 208 women who underwent abdominal hysterectomy received either cefazolin (N = 108) or moxalactam (N = 100) as perioperative antimicrobial prophylaxis. There were no differences between the two groups in rates of serious infection, minor wound infection, standard febrile morbidity, duration of hospitalization, proportion receiving other postoperative antibiotics, or rates of rehospitalization. Women who received moxalactam had significantly more urinary tract infections, 87% of which were caused by the enterococcus. It is concluded that perioperative prophylaxis with third-generation cephalosporins is not justified at this time.

Adult↗

Investigations on the potential nephrotoxicity of cefazedone and gentamicin and of their combination, in comparison with the combination of cefazolin and cephalothin with gentamicin.

The nephrotoxicity of (6R,7R)-7-(2-[3,5-Dichloro-4-oxo-1(4H)-pyridyl]-acetamido)-3-([(5-methyl-1,3,4-thiadiazol-2-yl)-thio]methyl)-8-oxo-5-thia-1-azabicyclo[4,2,0]oct-2-ene-2-carboxylic acid (cefazedone, Refosporen), cephalothin, cefazolin and gentamicin was investigated by the determination of alanine-amino-peptidase (AAP) in urine of healthy volunteers. The results were compared with those obtained by application of the respective combination. The beta-lactam antibiotics showed no effect on the elimination of the characteristic tubule enzyme, while gentamicin, as is known, induced a marked increase of the enzyme elimination. The results with cefazedone + gentamicin show that the determining component on the extent of AAP elimination is the aminoglycoside exclusively, where high and low responders can be observed. When the experiments with gentamicin and with the combination gentamicin and cefazedone were carried out with the same volunteers, no additive effects could be observed.

Adolescent↗