Experimental treatment of vascular graft infection due to Staphylococcus epidermidis by in situ replacement with a rifampin-bonded polyester graft.

In situ prosthetic graft replacement (ISPGR) of an infected prosthesis raises the risk of recurrent infection in the new graft, especially in cases involving drug-resistant microorganisms. The purpose of this animal study was to evaluate in situ replacement of a vascular graft infected by a highly rifampin-resistant strain of Staphylococcus epidermidis with the use of a rifampin-bonded polyester graft. Antibiotic bonding was obtained by soaking grafts in a high dose of rifampin solution (60 mg/mL). The infrarenal abdominal aorta of 20 dogs was replaced using a polyester prosthesis infected with a highly rifampin-resistant strain of Staphylococcus epidermidis. One week later, the 18 surviving animals were randomized into three groups. Group I (n = 6) did not undergo reoperation. Group II (n = 6) underwent ISPGR using a rifampin-bonded prosthesis. Group III (n = 6) underwent ISPGR using an untreated prosthesis. All surviving animals were killed 28 days after the first procedure. Infectious signs were noted and bacteriological study was carried out on explanted prostheses and various tissue samples. The findings of this experimental study show that soaking a polyester prosthesis in a high-dose rifampin solution can prevent reinfection after in situ replacement of a prosthesis infected by a highly rifampin-resistant Staphylococcus epidermidis.

[Phare study. Comparative study of combined cefepime-amikacin versus ceftazidime combined with amikacin in the treatment of nosocomial pneumonias in ventilated patients. Multicenter group study]. / Etude phare. Etude comparative de l'association céfépime-amikacine versus ceftazidime en association avec l'amikacine dans le traitement des pneumonies nosocomiales chez les patients ventilés. Le groupe multicentrique de l'étude.

OBJECTIVE: To compare the associations of cefepime (2 g x 2/day) + amikacin (7.5 mg.kg-1 x 2/day) (= cefe-ami) and ceftazidime (2 g x 3/day) + amikacin (7.5 mg.kg-1 x 2/day) (= cefta-ami) in patients under mechanical ventilation suffering from a nosocomial pneumonia. STUDY DESIGN: Multi-centre, open, comparative, randomised study. PATIENTS: The study included 275 ICU patients enrolled either in the cefe-ami group (n = 141) or in the cefta-ami group (n = 134). METHODS: All cases were reviewed in a blinded fashion by the steering committee. RESULTS: Microbiology laboratory tests were positive in 74% of patients of the cefe-ami group and in 63% of the cefta-ami group respectively; 319 presumed causative strains of bacteria were isolated. The mean duration of treatment was 12 days for cefepime, 11 days for ceftazidime and 8 days for amikacin. In intention to treat, the clinical recovery rate was 48.2% in the cefe-ami group and 44.8% in the cefta-ami group respectively. In the population with a documented pneumonia, the clinical recovery was significantly better in the cefe-ami group (53.3%), than in the cefta-ami group (39.3%) (P = 0.05). In per protocol analysis, these rates reached 67.7% in the cefe-ami group and 68.2% in the cefta-ami group respectively. In the bacteriologically documented cases the eradication rates were 86.5% and 89.3% respectively. CONCLUSION: The efficacy rates of cefe-ami and cefta-ami combinations were similar in ICU patients under mechanical ventilation with a nosocomial pneumonia. However the cefe-ami association was significantly more efficient in the population with a bacteriologically documented pneumonia.

Resistance of antibiotic-bonded gelatin-coated polymer meshes to Staphylococcus aureus in a rabbit subcutaneous pouch model.

This study examines the efficacy of the bonding of rifampicin, vancomycin or gentamicin to gelatin-coated knitted polymer meshes to prevent perioperative infection. Antibiotic bonding was obtained by soaking the meshes for 15 min in a solution containing 20 mg ml(-1) of rifampicin or 10 mg ml(-1) of vancomycin or gentamicin. A polymer mesh was implanted in a subcutaneous pouch in 16 rabbits: four received a rifampicin-soaked mesh, four received a vancomycin-soaked mesh, four received a gentamicin-soaked mesh, and four received an untreated mesh (control group). At the time of implantation, all the meshes were contaminated locally with 10(8) colony forming units of Staphylococcus aureus. Meshes were harvested one week later and submitted to bacterial counts. At the time of explantation, none of the antibiotic-soaked meshes were infected, whereas all the untreated meshes were infected. These results show that antibiotic soaking evidently prevents perioperative infection of gelatin-coated knitted polymer meshes in this model.

Treatment of vascular graft infection by in situ replacement with cryopreserved aortic allografts: an experimental study.

PURPOSE: The purposes of this study were to prove the efficacy of cryopreserved aortic allografts to treat an established vascular graft infection by in situ replacement in an animal model and to evaluate the role of the antibiotics normally used to decontaminate the allografts. METHODS: Twenty-three dogs underwent infrarenal aortic replacement with a gelatin-sealed knitted polyester graft contaminated in vitro by Staphylococcus epidermidis RP-62. One week later, the 18 surviving animals underwent reoperation for graft removal and were randomized into three groups for in situ replacement: group I (control, n = 6) received a new gelatin-sealed graft; group II (n = 6) received a non-antibiotic-treated cryopreserved allograft; and group III (n = 6) received an antibiotic-treated cryopreserved allograft. Control grafts and allografts were removed 4 weeks after the initial intervention for quantitative bacteriologic analysis and histologic analysis. Bacteriologic results were expressed as colony-forming units per square centimeter of graft material. Qualitative bacteriologic analysis was also obtained from perigraft fluid and tissue. RESULTS: All of the initially implanted grafts and all of the control grafts (group I) were infected at the time of removal. In group II, three out of six allografts were not totally incorporated, whereas in group III incorporation was always complete, with a significantly decreased inflammatory reaction. All of the antibiotic-treated allografts were sterile, whereas three untreated allografts grew bacteria. CONCLUSIONS: In this model, cryopreserved aortic allografts were more resistant to reinfection than synthetic grafts after in situ replacement of an infected prosthetic graft. However, the antibiotic loading of the cryopreserved aortic allograft appears to be essential to obtain optimal therapeutic effects.

[Thyroid nodules: assay of serum thyrotropin and cytopuncture versus scintigraphy as first-line tests. Prospective study with 150 cases]. / Nodules thyroïdiens: dosage d'hormone thyréotrope sérique et cytoponction versus scintigraphie comme examens de première intention. Etude prospective sur 150 observations.

OBJECTIVE: Fine-needle aspiration (FNA) is now considered as the first-line investigation for the diagnosis of thyroid nodules. We searched for a more accurate and cost-effective methodology as this technique fails to recognized hot nodules, frequent in certain countries. PATIENTS AND METHODS: A prospective study was conducted in 150 patients to compare two diagnostic procedures: scintigraphy first combined with FNA in case of cold nodules versus TSH measurement plus FNA when TSH measurement plus FNA when TSH was not depressed. The results were subjected to cost/benefit analysis. RESULTS: Cystic nodules were found in 28 cases (including 3 hyperfunctionning nodules, with 5 suspicious smears (1 carcinoma). FNA was non-diagnostic in 26 patients; 12 were operated on (1 carcinoma), 14 had further FNA (5 suspicious, 9 benign). Altogether 56 nodules were removed, for toxic adenoma (n = 5), for suspicious (n = 21) or malignant (n = 12) smear, or on personal (n = 18) demand; 16 carcinomas were found (2 medullary, 13 capillary, 1 follicular carcinomas). With scintigraphy first, the cost was 787 French francs (FF) per patient. With TSH measurement and FNA, the cost was 554 FF per patient. In both cases, the same number of carcinomas were removed, and all the hot nodules (11 including 5 toxic adenomas) were detected. CONCLUSION: Serum TSH measurement, with scintigraphy if TSH is low, and FNA in all the other cases, is accurate and more cost-effective than scintigraphy as a first-line investigation for the diagnosis of thyroid nodule.

Comparison of pulsed-field gel electrophoresis and randomly amplified DNA polymorphism analysis for typing extended-spectrum-beta-lactamase-producing Klebsiella pneumoniae.

The incidence and transmission patterns of extended-spectrum-beta-lactamase (ESBL)-producing Klebsiella pneumoniae in patients admitted to the intensive care unit (ICU) of a university hospital were investigated over a 3-year period. K. pneumoniae isolates were characterized by antibiotic susceptibility, capsular serotyping, plasmid profiles, and pulsed-field gel electrophoresis (PFGE) of genome macrorestriction patterns with XbaI, and the results were compared with those obtained by typing with the randomly amplified polymorphic DNA (RAPD) patterns. The discriminatory power of RAPD typing was evaluated for three primers. The incidence of isolation of ESBL-producing K. pneumoniae was 2.5 cases per 1,000 admissions to the ICU versus 0.35 cases per 1,000 admissions to other units (relative risk, 7.03; 95% confidence interval, 3.89 to 12.69). Infection developed in 53% of evaluable patients. Thirty-six percent of the cases were possibly acquired in other institutions. Isolates from ICU patients were subdivided into six capsular serotypes and into four clonal groups based on antibiotype, plasmid content, and PFGE and RAPD patterns. Two clones were associated with clusters of cross-infection, involving 5 and 12 patients, respectively. Following implementation of contact isolation precautions, the incidence of nosocomial acquisition of ESBL-producing K. pneumoniae decreased from 0.55 to 0.26 cases per 1,000 admissions (P = 0.03). PFGE and RAPD analysis showed concordant results and comparable discrimination for differentiation between groups of epidemiologically related strains of ESBL-producing K. pneumoniae. More subclonal variants were determined among epidemic clones by PFGE analysis than by RAPD analysis. Both methods are useful for typing K. pneumoniae strains in epidemiological investigations, although RAPD analysis is more efficient.

Arteries from human beings are less infectible by Staphylococcus aureus than polytetrafluoroethylene in an aortic dog model.

PURPOSE: Treatment of aortoiliac prosthetic graft infections includes the removal of the infected material and repeat revascularization if necessary. The risk of infection of the graft material used for the repeat revascularization has been the drawback of its use in situ except with autografts. Good results were obtained in this setting by use of in situ arterial allografts. The purpose of our study was to compare in vivo the infectibility of arteries used as allografts to the infectibility of commercially available prostheses. METHODS: Twelve dogs underwent thoracoabdominal aortic bypass with use of either an artery from a human being (n=6) or an expanded polytetrafluoroethylene (ePTFE) graft (n=6). One month later, bacteremia was produced with Staphylococcus aureus. One week after bacterial challenge, the animals were killed to recover the grafts. Each graft then underwent bacterial study. RESULTS: None of the arterial grafts grew bacteria, whereas four of the six ePTFE grafts (p < 0.05) did. In addition, none of the fragments of the arterial grafts grew bacteria, whereas 24 of the 60 ePTFE fragments (p < 0.01) did. CONCLUSION: Nonautologous arteries are less infectible than ePTFE in vivo. This decreased infectibility makes the arterial allograft an appealing material when revascularization must be performed in a contaminated field.

Interrelations between sex hormone-binding globulin (SHBG), plasma lipoproteins and cardiovascular risk.

The incidence of coronary artery disease is significantly higher in men than in women, at least until menopause. This gender difference could be explained by the action of sex steroids on the lipoprotein profile. In prepubertal children, high-density lipoprotein (HDL) cholesterol and triglyceride levels are similar between sexes, while adult men have generally lower HDL cholesterol and higher triglyceride levels than premenopausal adult women. Most cross-sectional studies have reported that sex hormone binding globulin (SHBG) and testosterone levels correlate positively with HDL cholesterol levels between sexes. Thus SHBG by modulating the balance in the biodisposal of testosterone and estradiol, might have a profound effect on the risk of cardiovascular disease. However, adjustment for body weight and body fat distribution weakens the association between SHBG, testosterone and HDL cholesterol. The negative correlation of fasting insulin with SHBG and HDL cholesterol levels in both sexes, and some evidence that insulin is an inhibitor of SHBG production in vitro, has suggested that hyperinsulinism might negatively regulate SHBG and HDL levels. It remains to be determined whether the inverse relationship between SHBG and insulin levels is coincidental or has a causal effect on the increase of atherosclerosis. Decreased SHBG has been shown to be predictive of the incidence of non-insulin-dependent diabetes mellitus in women but not in men, and of subsequent development of cardiovascular disease and overall mortality in postmenopausal women. SHBG is an index of androgenism in women and of insulin-resistance in both sexes, and might be useful in epidemiological studies of cardiovascular risk. However, in men, SHBG is not predictive of the occurrence of cardiovascular disease. Whether SHBG might have an intrinsic protective effect on the arterial wall through SHBG-receptors is still highly speculative.

Comparison of antibiotic combinations against penicillin-resistant pneumococci.

The isolation rate of penicillin resistant pneumococci is increasing in France. To date, cefotaxime and ceftriaxone are the two drugs recommended for the treatment of severe infections and oral third generation cephalosporins are frequently employed for the treatment of non-invasive pneumococcal diseases. In this study, we determined the bacteriostatic activity of 21 antibiotic combinations against 13 clinical isolates of Streptococcus pneumoniae with MICs > or = 0.1 mg/L penicillin and 13 strains that were susceptible.

Extended-spectrum beta-lactamase in Proteus mirabilis.

Over a period of one month, five isolates of Proteus mirabilis resistant to extended-spectrum cephalosporins colonized or infected five patients of the same intensive care unit. The antibiotic resistance phenotype and the metabolic profiles of the five strains were identical. All five produced a plasmid-mediated extended-spectrum beta-lactamase closely related to TEM-3/CTX-1 according to its pI (6.3), to its substrate profile and to the hybridization of the corresponding gene with blaTEM-3 specific oligonucleotide probes. Ability to produce this enzyme transferred by conjugation to Escherichia coli along with aminoglycoside and sulphonamide resistance. These resistance markers were encoded by a plasmid, (pAP1) which was identical in all five isolates but which was different from the TEM-3 beta-lactamase plasmids found in other Enterobacteriaceae. Plasmid pAP1 differed by its smaller size (47 kb), its EcoRI restriction pattern, its resistance co-markers (AAC(6') and sulphonamide only) and its much lower transfer frequency (2 x 10(-8)). Furthermore this plasmid did not belong to any known Enterobacteriaceae incompatibility group.

Use of cefotaxime or ceftazidime susceptibility tests for predicting susceptibility of Enterobacteriaceae and Pseudomonas aeruginosa.

To determine if susceptibility to aztreonam could be predicted from cefotaxime or ceftazidime disc diffusion testing, 919 Enterobacteriaceae and 187 Pseudomonas aeruginosa clinical strains were studied. The correlation coefficient between the diameters of inhibition zones was 0.9 for cefotaxime versus aztreonam and ceftazidime versus aztreonam comparisons in Enterobacteriaceae and 0.75 for ceftazidime versus aztreonam comparison in P. aeruginosa. For 99% of the Enterobacteriaceae, there was no risk in predicting susceptibility to aztreonam on the basis of cefotaxime or ceftazidime susceptibility tests. To minimize the risk of the remaining 1% of the strains being erroneously classified as susceptible to aztreonam, ceftoaxime should be tested in preference to ceftazidime, and the production of extended-spectrum beta-lactamases should be tested for using the cefotaxime-clavulanate disc synergy test. For P. aeruginosa strains, susceptibility to aztreonam could be accurately predicted from ceftazidime susceptibility tests for ticarcillin susceptible strains, but for ticarcillin resistant strains, susceptibility to aztreonam should be tested.

Treatment of vascular graft infection by in situ replacement with a rifampin-bonded gelatin-sealed Dacron graft.

PURPOSE: The purpose of this study was to treat an established prosthetic vascular graft infection by in situ replacement with a rifampin-bonded gelatin-sealed Dacron graft in an animal model. METHODS: The infrarenal aorta of 18 dogs was replaced with a gelatin-sealed graft contaminated in vitro by soaking it in a solution with Staphylococcus epidermidis. One week later, animals were randomized into three groups. In group I (control, (n = 6), the dogs did not undergo repeat operations. The dogs in groups II and III underwent repeat operation. In these animals the infected grafts were removed for bacteriologic analysis and replaced in situ with one of two types of grafts: group II (n = 6) received an untreated, gelatin-sealed graft; group III (n = 6) received a rifampin-bonded, gelatin-sealed graft. Antibiotic bonding was obtained by soaking grafts for 15 minutes in a 60 mg/ml saline solution of rifampin at 37 degrees C. All 18 dogs received no systemic adjunct antibiotic therapy. Control grafts and replacement grafts were removed 4 weeks after the initial implantation for bacteriologic analysis. When harvested, all the grafts were cut into two fragments, and quantitative bacterial cultures were obtained from all the fragments. Results were expressed as colony-forming units (CFU)/cm2 of graft material. RESULTS: All 18 initially implanted grafts and all the untreated replacement grafts were grossly infected at the time of removal, whereas all the rifampin-bonded replacement grafts had normal incorporation. None of the rifampin-bonded grafts grew bacteria, whereas all the initially implanted and all the untreated replacement grafts were infected (p < 0.01). Bacterial counts from the infected fragments were similar in control grafts (2.6 +/- 1.9 x 10(6) CFU/cm2), in initially implanted grafts of groups II (9 +/- 1.1 x 10(5) CFU/cm2) and III (1.3 +/- 1.5 x 10(6) CFU/cm2), and in untreated replacement grafts of group II (1.7 +/- 2.5 x 10(6) CFU/cm2). Blood culture results and culture results of liver, spleen, kidney, and lung specimens at the time of sacrifice were negative. CONCLUSION: This study demonstrates that rifampin-bonded gelatin-sealed Dacron grafts are resistant to infection when used for in situ replacement of an infected graft in the dog.

Prevention of gram negative nosocomial bronchopneumonia by intratracheal colistin in critically ill patients. Histologic and bacteriologic study.

OBJECTIVE: To evaluate the efficiency of intratracheal colistin in preventing nosocomial bronchopneumonia (BPN) in the critically ill. DESIGN: Study evaluating the clinical incidence of nosocomial BPN in 2 groups of critically ill patients who receive or did not receive intratracheal colistin. BPN was assessed clinically in survivors and histologically in non-survivors. SETTING: A 14-bed surgical intensive care unit. PATIENTS: 598 consecutive critically ill patients were studied during a prospective non-randomized study over a 40-month period. INTERVENTIONS: 251 patients--31 non-survivors and 220 survivors--did not receive intratracheal colistin and 347-42 non-survivors and 305 survivors--received intratracheal colistin for a 2-week period (1,600,000 units per 24 h). MEASUREMENTS AND RESULTS: The incidence of nosocomial BPN was evaluated clinically in survivors, using repeated protected minibronchoalveolar lavages, and histologically in non-survivors via an immediate postmortem pneumonectomy (histologic and semi-quantitative bacteriologic analysis of one lung). The clinical incidence of nosocomial BPN was of 37% in coli (-) survivors and of 27% in coli (+) survivors (p < 0.01). This result was histologically confirmed in non-survivors, where the incidence of histologic BPN was of 61% in coli (-) patients and of 36% in coli (+) patients (p < 0.001). Emergence of BPN due to colistin-resistant micro-organisms was not observed. Because colistin was successful in preventing Gram-negative BPN and did not change the absolute number of Gram-positive BPN, the proportion of BPN caused by staphylococcus species was higher in group coli (+) patients (33% vs 16%). Mortality was not significantly influenced by the administration of colistin. CONCLUSION: This study suggests that the administration of intratracheal colistin during a 2-week period significantly reduces the incidence of Gram-negative BPN without creating an increasing number of BPN due to colistin-resistant micro-organisms.

Selective decontamination of the digestive tract in neurosurgical intensive care unit patients: a double-blind, randomized, placebo-controlled study.

OBJECTIVES: The aim of this study was to assess, in a selected population, the effects of selective decontamination of the digestive tract on colonization of the oropharynx, trachea, stomach and rectum, and on the infection rate. An economical assessment was also performed. DESIGN: A prospective, double-blind, randomized, placebo-controlled, dual-center trial. SETTING: Two neurosurgical intensive care units. PATIENTS: A total of 191 comatose patients admitted emergently and intubated within < 24 hrs were enrolled. Of these patients, 68 were excluded because they either died, got an early infection, or were extubated within the first 5 days. A total of 123 patients were analyzed: 63 treated and 60 placebo patients. INTERVENTIONS: Topical antibiotics (tobramycin, polymyxin E, amphotericin B) were applied in the oropharynx and in the stomach. Vancomycin was added in the oropharyngeal paste. Placebo patients received the same regimen (i.e., a suspension of fluid and a paste) but without antibiotics. No parenteral antibiotics were given during the study period. MEASUREMENTS AND MAIN RESULTS: Bronchopneumonia episodes were diagnosed with protected specimen brush or plugged telescoping catheter and other infections were diagnosed according to the Center for Disease Control of Atlanta criteria. Antibiotic costs and cost per survivor were calculated. Selective decontamination of the digestive tract significantly reduced Gram-negative bacilli colonization as well as the number of episodes of bronchopneumonia, urinary tract infections, and sinusitis. Despite the addition of vancomycin, Staphylococcus aureus remained the main potential pathogen causing tracheal colonization and subsequent bronchopneumonia. The reduction in bronchopneumonia rate was observed in head-trauma patients only. We were able to show that: a) the trachea was the main reservoir of microorganisms responsible for pneumonia; b) pneumonia developed after tracheal colonization. Total charges for antibiotics were 2.8 times higher in the treated group than in the placebo group; in calculating the cost per survivor, selective decontamination of the digestive tract might be beneficial due to the reduced length of stay. CONCLUSIONS: Selective decontamination of the digestive tract is an effective technique in reducing infectious morbidity in comatose neurosurgical patients. Because of its cost, this technique should be used only in selected populations.

Penicillin-binding proteins of Rhodococcus equi: potential role in resistance to imipenem.

Rhodococcus equi is a gram-positive coccobacillus which, like other members of the order Actinomycetales, is increasingly reported as an opportunistic pathogen in patients with AIDS. The use of combinations of antibiotics that include imipenem (IMP) has been suggested for the treatment of patients infected with R. equi. An antagonism between IMP, meropenem, cefoxitin, ceftriaxone, moxalactam, and oxacillin and other beta-lactams, such as penicillin, amoxicillin, cephalothin, and ticarcillin, was detected in vitro both on Mueller-Hinton agar and in broth for all 10 IMP-susceptible R. equi strains examined. To study the mechanism of the antagonism between beta-lactams, a mutant with decreased susceptibility to IMP (isolate IpR) was selected in vitro from a susceptible clinical isolate of R. equi (isolate IpS). IpR exhibited decreased susceptibility to IMP, meropenem, cefoxitin, ceftriaxone, moxalactam, and oxacillin but not to penicillin, amoxicillin, cephalothin, or ticarcillin. No beta-lactamase was found in IpS, IpS cultured with antagonistic beta-lactams, or IpR strains. Labeling of penicillin-binding proteins (PBPs) revealed four PBPs with molecular masses of ca. 59, 56, 43, and 26 kDa in IpS. In IpR, PBP 3 disappeared and was replaced by PBP 3a of 40 kDa. The 50% saturation of PBP 3 and PBP 3a by the carbapenems correlated with the MICs of these antibiotics, respectively, for IpS and IpR strains. However, PBP 3a was not detected in IpS when IpS was cultured in the presence of beta-lactams, with which antagonism was observed. The present work describes the PBPs of R. equi and reports that IMP resistance in R. equi is related to an altered PBP pattern.