Identification of key pathways and genes in carotid atherosclerosis through bioinformatics analysis of RNA-seq data.

While acknowledging carotid atherosclerosis (CAS) as a risk factor for ischemic stroke, reports on its pathogenesis are scarce. This study aimed to explore the potential mechanism of CAS through RNA-seq data analysis. Carotid intima tissue samples from CAS patients and healthy subjects were subjected to RNA-seq analysis, which yielded, 1,427 differentially expressed genes (DEGs) related to CAS. Further, enrichment analysis (Gene Ontology, KEGG pathway, and MOCDE analysis) was performed on the DEGs. Hub genes identified via the protein-protein interaction network (PPI) were then analyzed using TRRUST, DisGeNET, PaGenBase, and CMAP databases. Results implicated inflammation and immunity in the pathogenesis of CAS. Also, lung disease was associated with CAS. Hub genes were expressed in multiple diseases, mainly regulated by RELA and NFKB1. Moreover, three small-molecule compounds were found via the CMAP database for management of CAS; hub genes served as potential targets. Collectively, inflammation and immunity are the potential pathological mechanisms of CAS. This study implicates CeForanide, Chenodeoxycholic acid, and 0317956-0000 as potential drug candidates for CAS treatment.

Glyphosate poisoning - a case report.

Glyphosate is the most commonly used broad-spectrum, non-selective herbicide in the world. The toxicity is supposed to be due to uncoupling of oxidative phosphorylation and the surfactant polyoxyethylene amine (POEA)- mediated cardiotoxicity. Clinical features of this herbicide poisoning are varied, ranging from asymptomatic to even death. There is no antidote and aggressive supportive therapy is the mainstay of treatment for glyphosate poisoning. We present a 69-year-old female patient with suicidal consumption of around 500 ml of Glycel®. Initially, gastric lavage was done and intravenous fluids were given. Within two hours of presentation, the patient developed respiratory distress needing intubation, hypotension needing vasopressor support, and severe lactic acidosis. She also developed acute respiratory distress syndrome, hypokalemia, hypernatremia, and aspiration pneumonia. Our patient was critically ill with multiple poor prognostic factors, but with timely aggressive supportive management, the patient gradually recovered.

Risk factors for postoperative pneumonia after cardiac surgery and development of a preoperative risk score*.

OBJECTIVES: The aims of this study were, first, to identify risk factors for microbiology-proven postoperative pneumonia after cardiac surgery and, second, to develop and validate a preoperative scoring system for the risk of postoperative pneumonia. DESIGN AND SETTING: A single-center cohort study. PATIENTS: All consecutive patients undergoing cardiac surgery between January 2006 and July 2011. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Multivariate analysis of risk factors for postoperative pneumonia was performed on data from patients operated between January 2006 and December 2008 (training set). External temporal validation was performed on data from patients operated between January 2009 and July 2011 (validation set). Preoperative variables identified in multivariate analysis of the training set were then used to develop a preoperative scoring system that was validated on the validation set. Postoperative pneumonia occurred in 174 of the 5,582 patients (3.1%; 95% CI, 2.7-3.6). Multivariate analysis identified four risk factors for postoperative pneumonia: age (odds ratio, 1.02; 95% CI, 1.01-1.03), chronic obstructive pulmonary disease (odds ratio, 2.97; 95% CI, 1.8-4.71), preoperative left ventricular ejection fraction (odds ratio, 0.98; 95% CI, 0.96-0.99), and the interaction between RBC transfusion during surgery and duration of cardiopulmonary bypass (odds ratio, 2.98; 95% CI, 1.96-4.54). A 6-point score including the three preoperative variables then defined two risk groups corresponding to postoperative pneumonia rates of 1.8% (score < 3) and 6.5% (score ≥ 3). CONCLUSION: Assessing preoperative risk factors for postoperative pneumonia with the proposed scoring system could help to implement a preventive policy in high-risk patients with a risk of postoperative pneumonia greater than 4% (i.e., patients with a score ≥ 3).

A sewing needle within the right hepatic lobe of an infant.

Intrahepatic foreign bodies are extremely rare before 6 months of age. We reported a case of a 5-month-old boy with a needle-like foreign body in the liver. The foreign body was incidentally found in the right hepatic lobe on the x-ray image. He was asymptomatic, with neither a history of swallowing a needle nor an abdominal cutaneous scar. Three-dimensional reconstruction of spiral computed tomographic scan showed an intrahepatic needle, close to the base of the heart, with its proximal end close to the gallbladder fossae. Because of the localization of the needle and subsequent risks of complications, surgical removal was recommended. At laparotomy, a tiny scar was recognized in the upper surface of the right lobe of the liver, confirming the migration route. Postoperative course was uneventful, and the child was discharged on postoperative day 10 and is thriving perfectly 2 months after surgery. We reviewed the clinical issues of intrahepatic foreign bodies and briefly discussed its approach and implications.

Prospective survey of acute osteoarticular infections in a French paediatric orthopedic surgery unit.

The epidemiology of acute paediatric osteoarticular infections (OAI) has recently evolved, mainly due to the improvement of microbiological diagnosis. We conducted a prospective study to analyse the recent epidemiology and the clinical evolution of paediatric OAI in order to validate the adequacy of our probabilistic first-line antibiotic treatment (intraveinous cefamandole + gentamicin). All children suspected of community acquired OAI were included and followed-up for 3 years. The etiologic diagnosis was based on blood cultures, joint aspirations and bone punctures. All osteoarticular (OA) samples were systematically inoculated into blood culture bottles. Real-time universal 16S rRNA and PCR targeted on Staphylococcus aureus, Kingella kingae, Streptococcus pneumoniae and Streptococcus pyogenes were performed twice a week. From 17 March 2007 to 26 February 2009, 98 septic arthritis, 70 osteomyelitis, 23 osteoarthritis and six spondylodiscitis were analysed. A portal of entry was suspected in 44% of cases, including 55% of otorhinolaryngological infections. C reactive protein was the most sensitive inflammatory marker. PCR increased by 54% the performance of bacteriological diagnosis. Among the patients completely investigated (blood culture and OAI samples), there were 63% documented OAI. The main pathogens found were K. kingae (52%), S. aureus (28%), S. pyogenes (7%), S. pneumoniae (3%) and Streptococcus agalactiae (2%). All isolated bacteria were sensitive to the probabilist treatment and outcome was favorable. PCR has significantly improved the performance and the delay of IOA diagnosis in children, for which K. kingae turned out to be the first causative agent. The probabilistic treatment was active against the main bacteria responsible for paediatric OAI.

Prevention of post-coccygectomy infection in a series of 136 coccygectomies.

Postoperative infection is a regular complication in coccygectomy. The authors propose the use of a topical skin adhesive on the postoperative wound as a contribution to the prevention of this complication. It was used on the first 56 patients in this study. The rate of infection was 3.6% compared with the 14% rate of infection in a previous study. The 80 following patients had, in addition to the skin adhesive, two prophylactic antibiotics for 48 hours (cefamandole and ornidazole), a preoperative rectal enema, and closure of the incision in two layers. The rate of infection dropped to 0.0%. Topical skin adhesive constitutes a significant contribution in the prevention of infection after coccygectomy.

[Primary peritonitis in Sub-Saharian Africa: a 15 case series]. / Péritonites primitives en Afrique subsaharienne: à propos de 15 cas.

Primary peritonitis (PP) is an infection of the peritoneal cavity occurring in the absence of a documented intraabdominal source of contamination. It is one of the main infectious complications of cirrhosis but is rare in healthy subjects. The purpose of this retrospective study is to describe a series of 15 cases of PP treated over a 3-year period at the Principal Hospital in Dakar, Senegal. The patient population was young (all but 2 under age of 13 years) and predominantly female (87%) with no predisposing factors. Clinical presentation always involved typical peritonitis. Surgical exploration was performed in all cases by laparotomy (n=13) or laparoscopy (n=2). Intra-operative bacteriologic sampling was performed systematically. Probabilistic antimicrobial therapy was administered in all cases using a triple-drug combination including a cephalosporin or betalactamine, an aminoside and metronidazole. This unconventional combination was designed to allow low-cost wide-spectrum coverage. As in patients with cirrhosis, the most common microbial agents were gram-negative bacteria (47%). Streptococcus pneumoniae was identified in 40% of cases. Infectious ORL and pulmonary sites were suspected in some cases. Although no supporting bacteriologic evidence was obtained, the high frequency of pneumococcal involvement as well as the age and female predominance of the patient population is consistent with contamination via the female genital tract. The cases in this series present unusual epidemiological, clinical and bacteriologic features. In Europe surgical treatment can be avoided thanks to the availability of modern facilities to support further laboratory examinations. In Africa antimicrobial therapy and peritoneal lavage are the mainstay treatments. Use of laparoscopy should be expanded.

IgA pemphigus--occurrence of anti-desmocollin 1 and anti-desmoglein 1 antibody reactivity in an individual patient.

BACKGROUND: IgA pemphigus is a rare pustular autoimmune disease with exclusive IgA anti-keratinocyte cell surface antibody reactivity. Two subtypes have been discerned: in the subcorneal pustular dermatosis type, desmocollin 1 has been identified as a targeted autoantigen, while in few cases of the intraepidermal neutrophilic type, IgA anti-desmoglein 1 or IgA anti-desmoglein 3 reactivity has been demonstrated. PATIENTS AND METHODS: A 48-year-old white male presented with generalized large confluent pustules. Skin pathology was assessed by histology and direct immunofluorescence analysis. IgG/IgA autoantibodies against desmoglein 1/3 and desmocollin 1 were measured by ELISA and indirect immunofluorescence using desmocollin 1 cDNA-transfected COS7 cells, respectively. RESULTS: Histopathology revealed subcorneal pustules and direct immunofluorescence microscopy exclusively showed in vivo bound IgA with an intercellular pattern in the epidermis. Desmocollin 1 was identified as a target of IgA autoantibodies by indirect immunofluorescence microscopy utilizing desmocollin 1 cDNA-transfected COS7 cells. In addition, IgA anti-desmoglein 1 reactivity was demonstrated by ELISA. Neither IgA anti-desmoglein 3 nor IgG anti-desmoglein 1/3 autoantibodies were present. CONCLUSIONS: Both desmocollin 1 and desmoglein 1 were autoantigens in this patient with IgA pemphigus and a distinct clinical presentation. To our knowledge, this is the first IgA pemphigus case with dual autoantibody reactivity.

Penetration of linezolid into bone, fat, muscle and haematoma of patients undergoing routine hip replacement.

Twelve patients undergoing total hip replacement were given 600 mg of linezolid as a 20 min iv infusion along with conventional prophylaxis of 1 g of cefamandole immediately before surgery. Routine total hip arthroplasty was carried out, and at timed intervals during surgery samples of bone, fat, muscle and blood were collected for assay by high-performance liquid chromatography analysis. Samples of the haematoma fluid that formed around the operation site and further blood samples for assay were also collected at timed intervals following the operation. The penetration of linezolid into bone was rapid, with mean concentrations of 9.1 mg/L (95% CI 7.7-10.6 mg/L) achieved at 10 min after the infusion, decreasing to 6.3 mg/L (95% CI 3.9-8.6 mg/L) at 30 min. Correction for the simultaneous blood concentrations gave mean values for bone penetration of 51% at 10 min, 60% at 20 min and 47% at 30 min. Although the penetration of linezolid into fat was also rapid, mean concentrations and degree of penetration were c. 60% of those in bone; at 10 min they were 4.5 mg/L (95% CI 3.0-6.1 mg/L; penetration 27%); at 20 min they were 5.2 mg/L (95% CI 4.0-6.4 mg/L; penetration 37%); and at 30 min, 4.1 mg/L (95% CI 3.3-4.8 mg/L; penetration 31%). For muscle the corresponding values were 10.4 mg/L (95% CI 8.1-12.7 mg/L; penetration 58%) at 10 min, 13.4 mg/L (95% CI 10.2-16.5 mg/L; penetration 94%) at 20 min and 12.0 mg/L (95% CI 9.2-14.8 mg/L; penetration 93%) at 30 min. Mean concentrations of linezolid in the haematoma fluid drained from around the operation site were 8.2 mg/L at 6-8 h and 5.6 mg/L at 10-12 h after the infusion, and 7.0 mg/L at 2-4 h following a second 600 mg infusion given 12 h post-operatively. We conclude that linezolid exhibits rapid penetration into bone, fat and muscle of patients undergoing hip arthroplasty, to achieve levels in excess of its MIC for susceptible organisms (< or=4 mg/L); therapeutic concentrations were maintained in the haematoma fluid that surrounds the operation site for >16 h.

[Infectious complications of mandibular osteotomy]. / Complications infectieuses des ostéotomies mandibulaires.

BACKGROUND: Infection is a rare complication after orthognathic surgery. A rate of 1% to 15% has been reported in the literature. We reviewed our experience. MATERIAL AND METHODS: We reviewed retrospectively 60 mandibular osteotomies performed between 1998 and 1999. There were 41 women and 19 men, mean age 24 years. All were given antibiotic therapy using cefamandol 1500 mg preoperatively then 750 mg every 6 hours peroperatively and cefixime 400 mg/d postoperatively for 7 days. Patients were followed for at least 6 months after surgery. RESULTS: There were 10 infections (16% of the cases) involving a hematoma in 2 cases, adenitis in 1, osteitis on a cortical fragment in 2 and osteitis on implanted material in 5. DISCUSSION: We defined infection following orthognathic surgery as a collection or purulent fistula with either a high polynuclear count in the discharge fluid or a positive culture. Both soft tissue (for example infection of a perimandibular hematoma) or bone infections were equally considered. We found two types of risk factors: patient-related or procedure-related. Patient-related factors included smoking, paradontal status, and dental hygiene. The main procedure-related factor was duration of surgery. Measures of prevention include extraction of the wisdom teeth, interruption of smoking, preoperative scaling and careful dental care, rigorous operative technique, antibiotic therapy.

Quinupristin-dalfopristin combined with beta-lactams for treatment of experimental endocarditis due to Staphylococcus aureus constitutively resistant to macrolide-lincosamide-streptogramin B antibiotics.

Quinupristin-dalfopristin (Q-D) is an injectable streptogramin active against most gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). In experimental endocarditis, however, Q-D was less efficacious against MRSA isolates constitutively resistant to macrolide-lincosamide-streptogram B (C-MLS(B)) than against MLS(B)-susceptible isolates. To circumvent this problem, we used the checkerboard method to screen drug combinations that would increase the efficacy of Q-D against such bacteria. beta-Lactams consistently exhibited additive or synergistic activity with Q-D. Glycopeptides, quinolones, and aminoglycosides were indifferent. No drugs were antagonistic. The positive Q-D-beta-lactam interaction was independent of MLS(B) or beta-lactam resistance. Moreover, addition of Q-D at one-fourth the MIC to flucloxacillin-containing plates decreased the flucloxacillin MIC for MRSA from 500 to 1,000 mg/liter to 30 to 60 mg/liter. Yet, Q-D-beta-lactam combinations were not synergistic in bactericidal tests. Rats with aortic vegetations were infected with two C-MLS(B)-resistant MRSA isolates (isolates AW7 and P8) and were treated for 3 or 5 days with drug dosages simulating the following treatments in humans: (i) Q-D at 7 mg/kg two times a day (b.i.d.) (a relatively low dosage purposely used to help detect positive drug interactions), (ii) cefamandole at constant levels in serum of 30 mg/liter, (iii) cefepime at 2 g b.i.d., (iv) Q-D combined with either cefamandole or cefepime. Any of the drugs used alone resulted in treatment failure. In contrast, Q-D plus either cefamandole or cefepime significantly decreased valve infection compared to the levels of infection for both untreated controls and those that received monotherapy (P < 0.05). Importantly, Q-D prevented the growth of highly beta-lactam-resistant MRSA in vivo. The mechanism of this beneficial drug interaction is unknown. However, Q-D-beta-lactam combinations might be useful for the treatment of complicated infections caused by multiple organisms, including MRSA.

[Alpha-1-antitrypsin in early infections after hip prosthesis surgery]. / L'alpha-1-antitrypsine dans les infections précoces après prothèse de hanche.

PURPOSE OF THE STUDY: The aim of this work was to determine whether erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and alpha-1-antitrypsin (A1AT) levels are correlated significantly with early postoperative infectious complications after hip prosthetic surgery. MATERIALS AND METHODS: This prospective study was conducted on 100 total hip replacements performed between 1994 and 1995. ESR, CRP and A1AT were obtained before surgery then at 1, 2 and 6 weeks after surgery. RESULTS: Seven bacteriologically proven cases of infection were reported. Infection was considered to be superficial if it did not extend deeper than the muscles fascia. There was a strong statistical correlation between A1AT level and infection for all postoperative times (p<0.0001). A1AT was highly sensitive (87.5 p. 100) and specific (85.8 p. 100) for infection compared with ESR (sensibility 70 p. 100 and specificity 65.9 p. 100) and CRP (sensitivity 63.6 p. 100 and specificity 80.1 p. 100). DISCUSSION AND CONCLUSION: In our hands, A1AT can be a most useful diagnostic tool for infection after prosthesis hip surgery. Although not totally specific, it is highly sensitive for infection compared with other tools such as ESR and CRP more frequently used. These findings suggest an avenue of research on the role of A1AT in infectious complications after prosthetic joint surgery.

[Antibiotic prophylaxis for high risk patients undergoing cholecystectomy]. / Fokozott kockázatú epemútétek antibiotikum profilaxisa.

An open, randomised clinical trial was performed on 435 high risk patients who underwent open cholecystectomy between 1 = January 1993. and 31. December 1995. The patients were divided into three groups. Group 1 (AMOX/CLAV, N = 179) was treated with 1.2 g i.v. amoxicillin/clavulanic acid, the patients in Group 2 (COMPARATOR, N = 164) were given other antibiotics commonly used for prophylaxis in biliary surgery (cefamandole, cefuroxime, cefotaxim). Group 3 (CONTROL, N = 92) contained patients without any risk factors for infectious complication. In this group we did not use antibiotic prophylaxis. The results were analysed with Student t, and x2 methods. The wound infection rate in Group 1 was 2.76% versus 5.48% in Group 2. The difference was significant if the patients were older than 65 years or the preoperative hospitalisation was longer than 5 days. The concentration of amoxycillin/calavulanic acid was measured in the serum, in the wall of the gall bladder, in the bile obtained both from the gall bladder and the major bile duct. The observed levels were higher than the therapeutic concentration in the serum and in the bile gained from the major bile duct, whereas lower in the gall bladder wall, and in the bile gained from the gall bladder. Systemic antibiotic prophylaxis is required for open cholecystectomy in high risk patients.

The impact of penicillinase on cefamandole treatment and prophylaxis of experimental endocarditis due to methicillin-resistant Staphylococcus aureus.

Beta-lactams active against methicillin-resistant Staphylococcus aureus (MRSA) must resist penicillinase hydrolysis and bind penicillin-binding protein 2A (PBP 2A). Cefamandole might share these properties. When tested against 2 isogenic pairs of MRSA that produced or did not produce penicillinase, MICs of cefamandole (8-32 mg/L) were not affected by penicillinase, and cefamandole had a > or =40 times greater PBP 2A affinity than did methicillin. In rats, constant serum levels of 100 mg/L cefamandole successfully treated experimental endocarditis due to penicillinase-negative isolates but failed against penicillinase-producing organisms. This suggested that penicillinase produced in infected vegetations might hydrolyze the drug. Indeed, cefamandole was slowly degraded by penicillinase in vitro. Moreover, its efficacy was restored by combination with sulbactam in vivo. Cefamandole also uniformly prevented MRSA endocarditis in prophylaxis experiments, a setting in which bacteria were not yet clustered in the vegetations. Thus, while cefamandole treatment was limited by penicillinase, the drug was still successful for prophylaxis of experimental MRSA endocarditis.

Influence of antibiotics on infection in spinal surgery: a prospective study of 110 patients.

The purpose of this prospective study was to evaluate the effect of prophylactic antibiotic treatment on postoperative antibiotic spinal wound infection after spinal surgery with instrumentation. Subjects consisted of 110 successive patients that underwent instrumented fusion with Cotrel-Dubousset (CD) or Miami Moss instrumentation. In 56 cases, the indication for surgery was painful spondylolisthesis. The remaining 54 patients were treated for idiopathic scoliosis. In total, 172 spinal procedures were performed and included in the study. Preoperative infection prophylaxis consisting of 2 g cefamandole was administered to all patients. Patients received three doses of 2 g/day cefamandole after surgery for 3 days. Follow-up ranged from 1 to 4 years. The study revealed an early infection in one (0.6%) of the 172 procedures in a patient with spondylolisthesis. A late infection occurred in one (0.6%) patient with the diagnosis of idiopathic scoliosis. In both cases, cultures were positive for Staphylococcus aureus.

[Antibiotic prophylaxis of infectious complications in gynecologic surgery]. / Antibiotická profylaxe infekcních komplikací v gynekologické operative.

Infections are still the most frequent postoperative complications and one of the limiting factors of successful gynaecological surgery. In recent years information on successful anti-microbial chemoprophylaxis is increasing and is associated with reduced postoperative inflammations, febrile morbidity and early complications. Views differ above all as regards indications for the use of antibiotic prophylaxis and the selection of a suitable antibiotic. Data in the literature differ also as regards achieved results. The submitted work had the objective to test on a representative group the success and rationality of medicamentous prophylaxis in gynaecological surgery and to contribute to a clearer view on controversial points. 203 women admitted to the Second Gynaecological and Obstetric Department of the First Medical Faculty Charles University and General Faculty Hospital Prague for elective abdominal or vaginal hysterectomy on account of a benign indication were divided into three groups which did not differ from the demographic or medical aspect. In group A (53 women) for prophylaxis two doses of Augmentin were used (combination of amoxycillin with clavulanic acid) i.v., patients in group M (50 women) had three doses of Mandol (Cefamandol) i.m., and in control group K (100 patients) no antibiotics were administered prophylactically. The authors investigated the postoperative course and evaluated some parameters in relation to possible postoperative infectious complications. The results proved unequivocally that prophylaxis with Augmentin reduces significantly the postoperative infectious morbidity (11.5%), febrile morbidity (5.6%) and the incidence of early infectious complications (3.8%) after abdominal or vaginal hysterectomy, as compared with the control group (35%, 31% and 11% resp.). Prophylaxis with Cefamandol reduced only in few parameters postoperative complications, but in general did not lead to a significant improvement of the postoperative course nor to a reduction of postoperative inflammatory complications. Similar results were obtained when only complications after abdominal hysterectomy were evaluated. The results of bacteriological examination confirmed the expected differences in the spectrum of efficacy of the two antibiotics on the most common microbial flora in the given area, i.e. a high sensitivity of Augmention to enterococci and bacterioids and resistance of these bacteria to Mandol. These results can be considered one of the reasons of different results of the two antibiotics. Prophylaxis with amoxycillin/clavulanic acid was found to be safe, very effective and financially feasible prevention of postoperative infectious complications after abdominal and vaginal hysterectomy. It led to a significant increase in the number of cases without any complications, when compared with the control group.

A comparison of the penetration of cefuroxime and cephamandole into bone, fat and haematoma fluid in patients undergoing total hip replacement.

Twelve patients undergoing total hip anthroplasty received, at the induction of anaesthesia, cephamandole (1 g) and cefuroxime (1.5 g); further doses of cephamandole (1 g) and cefuroxime (750 mg) were given at 8 and 16 h after the operation. Routine total hip arthroplasty was performed and at timed intervals during operation samples of bone, fat and blood were collected for assay for HPLC analysis. Samples of the haematoma fluid that formed around the operation site and further blood samples were also collected at 7 and 15 h after the operation. Although considerable variation was observed in the bone and fat concentrations of both agents, the cefuroxime levels were substantially higher than those of cephamandole, with mean values for bone of cefuroxime 36.0 mg/L (95% CI 29.0-43.0 mg/L) and cephamandole 18.3 mg/L (95% CI 14.2-22.4 mg/L) and for fat of cefuroxime 15.0 mg/L (95% CI 11.1-18.9 mg/L) and cephamandole 11.2 mg/L (95% CI 7.2-15.2 mg/L). When corrected for blood concentrations the penetration of both agents was similar (bone, 43.6% cefuroxime and 37.8% cephamandole; fat, 16.0% cefuroxime and 19.2% cephamandole). Cefuroxime concentrations in haematoma drain fluid were higher than those of cephamandole 6-8 h after the operation (17.8 versus 8.3 mg/L) but lower at 14-16 h (7.7 versus 9.6 mg/L). We conclude that there are no significant differences between the bone, fat or haematoma penetration of cefuroxime and cephamandole and that any differences in the absolute levels of the two agents are due to differences in the total drug administered rather than their ability to penetrate into these sites. Time-kill curves for cefuroxime and cephamandole against five clinical isolates of Staphylococcus aureus failed to identify any significant differences between the rates of kill for the two agents at the concentrations seen in bone, fat or haematoma fluid. For both prophylaxis regimens antibiotic concentrations exceeded the MICs for potential pathogens for the duration of the operation and also in the haematoma which surrounds the operation site for up to 24 h after the operation.

[Cefamandole for perioperative prophylaxis in total hip alloplasty]. / Cefamandol w profilaktyce okolooperacyjnej alloplastyki totalnej stawu biodrowego.

The aim of this paper was to present the use of Cefamandole as one of the elements in perioperative prophylactics in total hip replacement. One hundred patients operated between 1993 and 1995 were followed-up for mean 13.5 months. There were 33 males and 67 females, mean age was 61.4 years. Cefamandole was administered according to fixed protocol for three days (first dose along with premedication). Mono-antibiotic therapy was sufficient in most cases. No septic complication occurred, no side-effects of Cefamandole were recorded. The patients are still being followed-up. Results achieved resemble these from the literature so conclusion can be made, that Cefamandole is safe and efficient drug for peri-operative prophylactics in total hip replacement.

Synergistic effect of a recombinant N-terminal fragment of bactericidal/permeability-increasing protein and cefamandole in treatment of rabbit gram-negative sepsis.

As a consequence of their bactericidal actions, many antibiotics cause the release of endotoxin, a primary mediator of gram-negative sepsis. Bactericidal/permeability-increasing protein (BPI) has bactericidal activity and neutralizes endotoxin in vitro and in vivo. We sought to examine the effect of a recombinant N-terminal fragment of BPI (rBPI21) in conjunction with cefamandole, a cephalosporin antibiotic, in the treatment of Escherichia coli bacteremia and septic shock in rabbits. Cefamandole (100 mg/kg of body weight) was injected intravenously. This was followed by simultaneous 10-min infusions of E. coli O7:K1 (9 x 10(9) CFU/kg) and rBPI21 (10 mg/kg). rBPI21 was continuously infused for an additional 110 min at 10 mg/kg/h. The administration of rBPI21 in conjunction with the administration of cefamandole prevented the cefamandole-induced increase of free endotoxin in plasma, accelerated bacterial clearance, ameliorated cardiopulmonary dysfunction, and thereby, prevented death, whereas neither agent alone was protective in this animal model. The efficacy of the combined treatment with rBPI21 and cefamandole suggests a synergistic interaction between the two agents. The data indicate that rBPI21 may be useful in conjunction with traditional antibiotic therapy.