Cephalosporin susceptibility of Staphylococcus aureus strains isolated from commercial rabbit and goats farms in Spain.

Antimicrobial drug resistance is an important problem that challenges veterinary clinicians to provide effective treatments without further spreading resistance to other animals and people. The most commonly used pharmacodynamic parameter to define potency of antimicrobial drugs is minimum inhibitory concentration (MIC). The aim of this study was to evaluate the antibiotic susceptibility of thirty-six strains of Staphylococcus aureus isolated from dairy goats with mastitis and rabbits with chronic staphylococcosis. Four cephalosporins were tested: cephalexin, cephalotin, cefonicid and ceftiofur. MIC tests were performed according to the microdilution broth method. The calculated values of sensitivity in goats and rabbits were 66.67% and 72.22% for cephalexin, 72.22 % and 94.44% for cefonicid, 77.78% and 94.44% for cephalotin and 77.78% and 100% for ceftiofur, respectively. For all antibiotics, MIC90 of S. aureus from rabbits were lower than MIC90 from goats. These data suggest that more antibiotics are used in goat milk production than in rabbit farming. According to MIC values obtained in this study, ceftiofur and cephalotin may be the best option for treating S. aureus infections in lactating goats. For rabbits, ceftiofur showed lowest MIC values, therefore, it could be an alternative to treatment the infections caused by S. aureus in this species.

Pharmacokinetics of cefonicid in lactating goats after intravenous, intramuscular and subcutaneous administration, and after a long-acting formulation for subcutaneous administration.

The single-dose disposition kinetics of cefonicid were determined in clinically normal lactating goats (n = 6) after intravenous (IV), intramuscular (IM) and subcutaneous (SC) administration of a conventional formulation, and after subcutaneous administration of a long-acting formulation (SC-LA). Cefonicid concentrations were determined by high performance liquid chromatography with ultraviolet detection. The concentration-time data were analysed by noncompartmental pharmacokinetic methods. Steady-state volume of distribution (Vss ) and clearance (Cl) of cefonicid after IV administration were 0.14 ± 0.03 L/kg and 0.51 ± 0.07 L/h·kg, respectively. Following IM, SC and SC-LA administration, cefonicid achieved maximum plasma concentrations of 14.46 ± 0.82, 11.98 ± 1.92 and 17.17 ± 2.45 mg/L at 0.26 ± 0.13, 0.42 ± 0.13 and 0.83 ± 0.20 hr, respectively. The absolute bioavailabilities after IM, SC and SC-LA routes were 75.34 ± 11.28%, 71.03 ± 19.14% and 102.84 ± 15.155%, respectively. After cefonicid analysis from milk samples, no concentrations were found above LOQ at any sampling time. From these data, cefonicid administered at 20 mg/kg each 12 hr after SC-LA could be effective to treat bacterial infections in lactating animals not affected by mastitis problems.

A successful treatment of necrotizing fasciitis following the surgery of distal radius plate removal: A case report and literature review.

RATIONALE: Necrotizing fasciitis (NF) is defined as a rare, rapidly progressive, and highly lethal skin infection characterized by necrosis of the fascia and subcutaneous tissue. PATIENT CONCERNS: The present study aims to discuss the case of a 35-year-old man who developed NF following a routine sterile right distal radius bone plate removal surgery. DIAGNOSES: The patient was suspected of NF based on his clinical manifestations, laboratory tests, and imaging results. The diagnosis of NF was confirmed by histological examinations. INTERVENTIONS: Serial prompt and extensive debridement was performed during the rapid and aggressive extension of the skin infection, together with antibiotics and supportive treatments. OUTCOMES: The condition of the patient finally improved on the sixth day of disease progression. Skin grafting of his right forearm wound was performed successfully 2 months after the admission. LESSONS: NF can occur during the perioperative period for routine clean radius plate removal operation in patients with no risk factor for NF. The objective is to remind the physicians to stay aware of this disease, especially its early clinical signs and symptoms. Urgent subsequent treatment, including surgical debridement, antibiotic therapy, and supporting management, is the key to ensure the survival and better prognosis of patients.

Influencia del manguito de isquemia en la profilaxis antibiótica en prótesis total de rodilla / Influence of the ischaemic tourniquet in antibiotic prophylaxis in total knee replacement

Objetivo. Existe evidencia científica grado iv de la importancia que el antibiótico administrado preoperatoriamente tiene en la prevención de la infección protésica. Hay controversia en si la isquemia aplicada en la cirugía de estos pacientes puede afectar a la concentración mínima inhibitoria del antibiótico en los tejidos periprotésicos. Para estudiar este fenómeno hemos diseñado un estudio basado en la determinación de la concentración de antibiótico en el tejido sinovial. Material y método. Estudio clínico prospectivo observacional de 32 pacientes intervenidos de prótesis total de rodilla. Se administró 2 g de cefonicid como profilaxis y se utilizó el manguito de isquemia en todos los pacientes, cuantificándose la concentración antibiótica mediante la cromatografía líquida de alta resolución en muestras de tejido sinovial del inicio y del final de la intervención. Resultados. La concentración media de antibiótico fue de 23,16 μg/g (IC del 95%, 19,19-27,13) en las muestras del inicio de la intervención y de 15,45 μg/g (IC del 95%, 13,20-17,69) en las muestras del final, mostrándose superiores a la concentración mínima inhibitoria del cefonicid, establecida en 8 μg/g, siendo estos resultados estadísticamente significativos para ambas concentraciones (p < 0,00001). Discusión. La concentración de antibiótico a lo largo de una intervención estándar de prótesis total de rodilla realizada con isquemia preventiva varía a lo largo de la intervención sufriendo un descenso paulatino. Aun así, la concentración determinada al final de la intervención no fue inferior a la concentración mínima inhibitoria del antibiótico estudiado. Como conclusión, la utilización del manguito de isquemia no aumenta el riesgo de infección (AU)

Objective. There is level iv evidence that the preoperative administration of antibiotics helps in the prevention of prosthetic infection. There is controversy on whether the ischemia applied during surgery may affect the minimum inhibitory concentration of the antibiotic in the peri-prosthetic tissues. The aim of this study is to review this phenomenon through the determination of antibiotic concentration in the synovial tissue. Material and method. A prospective observational clinical study was conducted on 32 patients undergoing total knee replacement. Cefonicid 2 g was administered as prophylaxis, with a tourniquet used for all patients. The antibiotic concentration was quantified by high performance liquid chromatography in samples of synovial tissue collected at the beginning and at the end of the intervention. Results. The mean concentration of antibiotic was 23.16 μg/g (95% CI 19.19 to 27.13) in the samples at the beginning of the intervention and 15.45 μg/g (95% CI 13.20 to 17.69) in the final samples, being higher than the minimum inhibitory concentration of cefonicid, set at 8 μg/g. These results were statistically significant for both concentrations (P<.00001). Discussion. The antibiotic concentration throughout the standard total knee prosthesis surgery performed with tourniquet gradually decreases throughout the intervention. The concentration determined at the end of the intervention was higher than the minimum inhibitory concentration required for the antibiotic studied. In conclusion, the use of a tourniquet does not increase the risk of infection (AU)

Influence of the ischaemic tourniquet in antibiotic prophylaxis in total knee replacement.

OBJECTIVE: There is level iv evidence that the preoperative administration of antibiotics helps in the prevention of prosthetic infection. There is controversy on whether the ischemia applied during surgery may affect the minimum inhibitory concentration of the antibiotic in the peri-prosthetic tissues. The aim of this study is to review this phenomenon through the determination of antibiotic concentration in the synovial tissue. MATERIAL AND METHOD: A prospective observational clinical study was conducted on 32 patients undergoing total knee replacement. Cefonicid 2g was administered as prophylaxis, with a tourniquet used for all patients. The antibiotic concentration was quantified by high performance liquid chromatography in samples of synovial tissue collected at the beginning and at the end of the intervention. RESULTS: The mean concentration of antibiotic was 23.16 µg/g (95% CI 19.19 to 27.13) in the samples at the beginning of the intervention and 15.45 µg/g (95% CI 13.20 to 17.69) in the final samples, being higher than the minimum inhibitory concentration of cefonicid, set at 8 µg/g. These results were statistically significant for both concentrations (P<.00001). DISCUSSION: The antibiotic concentration throughout the standard total knee prosthesis surgery performed with tourniquet gradually decreases throughout the intervention. The concentration determined at the end of the intervention was higher than the minimum inhibitory concentration required for the antibiotic studied. In conclusion, the use of a tourniquet does not increase the risk of infection.

Substitute technology for reference substances in the analysis of impurities in cefonicid for injection with HPLC using a diode array detector.

With HPLC using a diode array detector (DAD), a method of substitution for reference substances in impurity profiling control was developed that combined peak tracking by the correlation of spectra with application of correction factors for determination of each impurity. For qualitative analysis, two-dimensional (2D) standard spectrochromatographic data produced by HPLC-DAD were compared with sample data to develop 2D chromatographic spectral correlative maps so that the three target impurities were recognized without preparation and injection of reference solutions. For quantitative analysis, correction factors among cefonicid and the three impurities were established. The correction factors were 1.06 for 5-mercapto-1,2,3,4-tetrazole 1-methyl sulfonic acid detected at 255 nm, 0.77 for 7-aminocephalosporanic acid detected at 265 nm, and 0.97 for methoxycefonicid detected at 268 nm. The method could be used in analysis of related substances in cefonicid for injection without recourse to chemical reference standards of the three impurities.

Enteropathogenic Bacteria Contamination of Unchlorinated Drinking Water in Korea, 2010

OBJECTIVES: The purpose of this study was to assess the microbiological quality of unchlorinated drinking water in Korea, 2010. One hundred and eighty unchlorinated drinking water samples were collected from various sites in Seoul and Gyeonggi province. METHODS: To investigate bacterial presence, the pour plate method was used with cultures grown on selective media for total bacteria, total coliforms, and Staphylococcus spp., respectively. RESULTS: In the 180 total bacteria investigation, 72 samples from Seoul and 33 samples from Gyeonggi province were of an unacceptable quality (>10(2) CFU/mL). Of all the samples tested, total coliforms were detected in 28 samples (15.6%) and Staphylococcus spp. in 12 samples (6.7%). Most of the coliform isolates exhibited high-level resistance to cefazolin (88.2%), cefonicid (64.7%) and ceftazidime (20.6%). In addition, Staphylococcus spp. isolates exhibited high-level resistance to mupirocin (42%). Species of Pseudomonas, Acinetobacter, Cupriavidus, Hafnia, Rahnella, Serratia, and Yersinia were isolated from the water samples. CONCLUSIONS: The results of this study suggest that consumption of unchlorinated drinking water could represent a notable risk to the health of consumers. As such, there is need for continuous monitoring of these water sources and to establish standards.

Empiric treatment with once-daily cefonicid and gentamicin for febrile non-neutropenic pediatric cancer patients with indwelling central venous catheters.

SUMMARY: The approach to treating febrile non-neutropenic hematooncologic patients with central venous catheters varies. We recently introduced once-daily administration of cefonicid and gentamicin for such children who were in good clinical condition and without focal signs of infection. Our 2-year experience of 125 episodes in 54 children is hereby reported. Absolute neutrophil counts were 550 to 16,700/mm. Bacteremia occurred in 6.4% episodes: only in patients with Hickman/Broviac catheters and not in those with port-a-caths [8/37 (21.6%) vs. 0/17 patients, P=0.046; 8/86 (9.3%) vs. 0/39 episodes, P=0.056]. The pathogens were coagulase-negative staphylococci (3), Streptococcus pneumoniae (2), Pseudomonas aeruginosa and Klebsiella pneumoniae (1), methicillin-sensitive Staphylococcus aureus (1), and Streptococcus milleri (1). All patients remained in stable clinical condition and all, except for 2 who became neutropenic and 1 with S. aureus bacteremia who developed cellulitis, defervesced while on the empiric therapy. Three episodes could not be managed as outpatients. No adverse effects were observed. We conclude that our approach is efficacious and safe and, furthermore, that empiric antibiotic therapy may not be indicated for selected patients with port-a-caths. Future study of children with Hickman/Broviac catheters will evaluate the use of cefonicid alone.

Characteristics of microorganisms cultured from infected wounds post-hysterectomy.

OBJECTIVE: To characterize organisms causing wound infection following abdominal hysterectomy. STUDY DESIGN: All patients who underwent an abdominal hysterectomy (December 2002-January 2006) and developed abdominal wall wound infection proven by a positive culture were included in the study. Patient information was collected from the computerized files. The isolated microorganisms were characterized for antibiotics susceptibility. RESULTS: Sixty-eight (68/620, 10.96%) patients had positive wound cultures. Of 100 isolated microorganisms, 44 were resistant to cefonicid (prophylactic treatment) and 15 were resistant to combined ampicillin, gentamicin and metronidazole (empirical treatment). Major co-morbidities (including diabetes mellitus, hypertension, past malignancies, renal, cardiovascular and pulmonary diseases, hypothyroidism or anemia), were found to be significantly associated with pseudomonal infection (P<.008). CONCLUSION: A significant portion of pathogens causing post-hysterectomy abdominal wall wound infection are resistant to the prophylactic treatment, and some are resistant to the empirical treatment. Further studies are necessary to evaluate the effectiveness of various prophylactic regimens with better coverage of Enterococcus fecalis, as well as the effectiveness of empirical treatment active against the resistant Enterobacteriaceae group.

Solid-state chemistry and particle engineering with supercritical fluids in pharmaceutics.

The present commentary aims to review the modern and innovative strategies in particle engineering by the supercritical fluid technologies and it is principally concerned with the aspects of solid-state chemistry. Supercritical fluids based processes for particle production have been proved suitable for controlling solid-state, morphology and particle size of pharmaceuticals, in some cases on an industrial scale. Supercritical fluids should be considered in a prominent position in the development processes of drug products for the 21st century. In this respect, this innovative technology will help in meeting the more and more stringent requirements of regulatory authorities in terms of solid-state characterisation and purity, and environmental acceptability.

Determination of cefonicid in human urine by adsorptive square-wave stripping voltammetry.

The adsorption behavior of cefonicid on the hanging mercury drop electrode (HMDE) has been examined using cyclic voltammetry and square-wave voltammetry techniques in Britton-Robinson (B-R) buffers in the pH range of 2.0-11.0. The effect of different parameters on the accumulation behavior of the adsorbed species has been evaluated. Sensitive measurements can be achieved after controlled adsorption on the surface of HMDE followed by square-wave voltammetry. Under optimal conditions, a detection limit of 4.0 x 10(-8) M and a linear calibration graph in the range 1.0 x 10(-7)-1.0 x 10(-6) M were obtained. Direct simple determination of cefonicid in urine was established with no manipulation of urine sample other than dilution and subsequent adsorptive stripping voltammetric determination. The detection limit of the method was 1.0 microg x ml(-1) of cefonicid in urine.

Comparative clinical study of cefonicid, chloramphenicol, and penicillin in community-acquired pneumonia.

Community-acquired pneumonia is one of the most common infectious conditions that require hospitalization. When intravenous treatment is indicated, cefonicid is usually the drug of choice. The aim of this study was to find out if chloramphenicol, which is superior to the standard drugs from a financial point of view, could serve as an equally efficient treatment, especially in the elderly. The outcomes of 3 pneumonia patient groups who were either treated with cefonicid, chloramphenicol or penicillin-G (n = 59, 17, 24, respectively) were retrospectively compared. Data about demographic characteristics of the patients, clinical outcomes, rehospitalization rates, duration of improvement/treatment/ hospitalization and clinical laboratory tests were obtained from each patient's medical records. Only minor differences (even though occasionally significant) were found with respect to rehospitalization and improvement rates, duration of hospitalization, treatment and improvement, death rates and clinical laboratory tests. However, chloramphenicol patients were found to be significantly older than cefonicid patients. Moreover, no bone-marrow suppression was associated with chloramphenicol treatment. All 3 drugs tested seem to have the same efficacy. We conclude that since chloramphenicol is as safe as, and much cheaper than cefonicid, this antibiotic agent is not inferior to the others, its usage in older patients with pneumonia should be considered.

Prospective, randomized, double-blind study of prophylactic antibiotics in axillary lymph node dissection.

BACKGROUND: Antibiotic prophylaxis is controversial in patients undergoing axillary lymph node dissection (ALND). We determined whether preoperative antibiotics decreased incidence or treatment cost of infectious complications following ALND. METHODS: Two hundred patients entered this prospective, randomized, double-blind trial. Patients received either placebo or cefonicid preoperatively. Loco-regional signs of infection were monitored for 4 weeks postoperatively. RESULTS: There was a trend toward fewer infections in the prophylactic group (placebo 13% versus cefonicid 6%; P = 0.080). Cefonicid significantly decreased severe infections requiring hospitalization (placebo 8% versus cefonicid 1%; P = 0.033). Cefonicid also decreased the treatment cost of infection per patient ($49.80 versus $364.87). CONCLUSIONS: We demonstrated a trend toward fewer overall infections and significantly fewer severe infections in patients given prophylactic antibiotics, which translated into a decrease in the cost of treatment for infectious complications. These findings support antibiotic prophylaxis for patients undergoing ALND.

Cefonicid 'restores' the depressed activities of polymorphonuclear cells from chronic haemodialysis patients and renal transplant recipients in vitro.

BACKGROUND: Chronic haemodialysis patients and renal transplant recipients are highly susceptible to infection characterized by high morbidity and mortality and related to an impairment of the phagocytic response. SUBJECTS AND METHODS: In order to elucidate how cefonicid, a cephalosporin with a broad spectrum of activity and once-daily dosage, influences this phagocytic response, the effects of the drug upon the functions of human PMNs from both healthy individuals and immunocompromised patients were investigated. RESULTS: In vitro, PMNs from haemodialysed patients and renal transplant recipients showed a diminished phagocytic efficiency with reduced phagocytosis and bactericidal activity towards intracellular Klebsiella pneumoniae when compared with that seen in PMNs from healthy subjects. Cefonicid significantly affected the activity of PMNs from healthy volunteers, resulting in either an increased percentage of ingested klebsiellae or a reduced intracellular bacterial load when compared with the control, drug-free system. When cefonicid was added to PMNs from uraemic patients a pattern similar to that observed with phagocytes from healthy subjects was detected: the antibiotic was able to 'restore' the depressed primary functions of PMNs, resulting in a significant increase in both phagocytosis and killing activity. CONCLUSIONS: Cefonicid, with its several immunoproperties observed in this study, possesses interesting beneficial properties which make it suitable for the treatment of infections in patients with impaired components of the immune system.

Treatment of staphylococcal septic arthritis in rabbits by systemic antibiotics and intra-articular corticosteroids.

OBJECTIVE: To assess the effect of intra-articular corticosteroids added to systemic antibiotics in experimental septic arthritis. METHODS: Rabbits were injected intra-articularly by Staphylococcus epidermidis. Rabbits received no additional treatment and served as control (group 1), were treated with systemic antibiotics (group 2), or treated with systemic antibiotics and intra-articular corticosteroids (group 3). After 15 days animals were killed and joint histopathological-histochemical parameters were assessed. RESULTS: All rabbits survived the experiment. The treated groups (2-3) had lower histological-histochemical scores in comparison with the untreated group (1). Group 3 had significantly lower scores in joint sections in comparison with group 2: (mean (SD) 6.5 (1.4) v 4.0 (1.0), p = 0.001 and 7.4 (2.6) v 4.2 (2.2), p = 0.01), because of lower damage expressed in clustering of chondrocytes, pannus formation, proteoglycan depletion, and synovitis. CONCLUSION: Addition of local corticosteroids to systemic antibiotics in septic arthritis seems to be harmless, and improves joint histological-histochemical parameters in this experimental setting.

Antibiotic prophylaxis in umbilical and incisional hernia repair: a prospective randomised study.

OBJECTIVE: To find out if preoperative prophylaxis would reduce infection rates after umbilical and incisional hernia repair. DESIGN: Randomised controlled trial. SETTING: Teaching hospital, Israel. SUBJECTS: 35 Patients who presented with umbilical (n = 19) or incisional (n = 16) hernias during a period of 8 months. INTERVENTIONS: Cefonicid 1 g was given by intravenous infusion to alternate patients 30 minutes before the operation. MAIN OUTCOME MEASURES: Wound infection. RESULTS: The groups were comparable for age, body mass index, grade of surgeon, operating time, and size of hernial ring. The wound infection rates were 0/8 compared with 4/8 for incisional hernia repairs (p = 0.08) and 1/9 compared with 4/10 for umbilical hernia repairs (p = 0.3). The overall rate was 1/17 compared with 8/18 (p = 0.02). CONCLUSIONS: Single dose antibiotic puphylaxis seems to exert a beneficial effect on the wound infection rate after umbilical and incisional hernia repair.

Acute bacterial peritonitis: permeability of cephalosporins in the peritoneal cavity.

Acute bacterial peritonitis is a common surgical disease treated with fluid resuscitation, surgery and antibiotics. The choice and use of antibiotics is an important supplement of therapy. Cephalosporins are among the most frequently used drugs for this condition. Although there is evidence that these agents reach the peritoneal cavity under normal conditions, no data are available regarding their delivery and concentration during acute secondary bacterial peritonitis. In order to determine the effectiveness of these agents in such cases, we studied the diffusion of three generations of cephalosporins--cefazolin, cefonicid and cefotaxime--into the peritoneal cavity during controlled bacterial peritonitis in rats. Our results show that all three drugs reached therapeutic concentrations in the peritoneal fluid; the highest concentration was obtained by the third-generation cefotaxime.