Efficacy of teicoplanin and autoradiographic diffusion pattern of [14C]teicoplanin in experimental Staphylococcus aureus infection of joint prostheses

Prosthesis infections are difficult to cure. Infection with methicillin-resistant staphylococci is becoming more common in patients with orthopedic implants. Using a recently developed model of methicillin-resistant Staphylococcus aureus (MRSA) infection of a knee prosthesis, we compared the efficacies of teicoplanin and vancomycin. [14C]teicoplanin diffusion in this model was also studied by autoradiography. A partial knee replacement was performed with a silicone implant fitting into the intramedullary canal of the tibia, and 10(7) CFU of MRSA was injected into the knee. Treatment with teicoplanin or vancomycin (20 or 60 mg/kg of body weight, respectively, given intramuscularly twice daily) was started 7 days after inoculation and was continued for 7 days. The teicoplanin and vancomycin MICs for MRSA were 1 microg/ml. Mean peak and trough levels in serum were 39.1 and 23.5 microg/ml, respectively, for teicoplanin and 34.4 and 18.5 microg/ml, respectively, for vancomycin. Fifteen days after the end of therapy, the animals were killed and their tibias were removed, pulverized, and quantitatively cultured. Teicoplanin and vancomycin significantly reduced (P < 0. 05) the bacterial density (2.7 +/- 1.3 and 3.3 +/- 1.6 log10 CFU/g of bone, respectively) compared to those for the controls (5.04 +/- 1.4 log10 CFU/g of bone). The bacterial covents of teicoplanin- and vancomycin-treated rabbits were comparable. The [14C]teicoplanin autoradiographic diffusion patterns in rabbits with prostheses, two of which were uninfected and two of which were infected, were studied 15 days after inoculation. Sixty minutes after the end of an infusion of 250 microCi of [14C]teicoplanin, autoradiography showed that in the infected animals, the highest levels of radioactivity were located around the prosthesis and in the periosteum, bone marrow, and trabecular bone. Radioactivity was less intense in epiphyseal disk cartilage, femoral cartilage, articular ligaments, and muscles and was weak in compact bone. A similar distribution pattern was seen in uninfected rabbits. Thus, teicoplanin may represent an effective alternative therapy for the treatment of these infections.     

Activity of fleroxacin alone and in combination with clindamycin or metronidazole in experimental intra-abdominal abscesses

To assess the potential efficacy of fleroxacin in combination with clindamycin or metronidazole in mixed aerobic and anaerobic infections, we used a rat model of intra-abdominal abscesses in which the inoculum consisted of pooled rat feces mixed with BaSO4. Two hours after bacterial challenge, antimicrobial therapy was begun intravenously with regimens designed to stimulate human pharmacokinetics. A combination of clindamycin and gentamicin was included as an established treatment regimen. After 8.5 days of therapy, final bacterial counts in abscesses showed that fleroxacin alone or combined with metronidazole or clindamycin effectively eradicated Escherichia coli, with bacterial densities of < or = 2.84 +/- 0.1, < or = 2.9 +/- 0.1, and < or = 2.9 +/- 0.1 (mean +/- standard error of the mean) log10 CFU/g, respectively. The addition of either clindamycin or metronidazole to fleroxacin substantially enhanced the effectiveness of the regimens against Bacteroides fragilis, with bacterial counts of < or = 3.0 +/- 0.1 or < or = 2.9 +/- 0.1 log10 CFU/g, respectively, versus 9.2 +/- 0.2 log10 CFU/g for fleroxacin alone. The combination of metronidazole and fleroxacin also resulted in a significantly greater reduction of peptostreptococci and Bacteroides thetaiotaomicron than fleroxacin alone (< or = 2.9 +/- 0.1 versus 6.1 +/- 0.9 log10 CFU/g and 3.3 +/- 0.4 versus 8.3 +/- 0.1 log10 CFU/g, respectively). Except for those of B. fragilis, counts of other anaerobes were reduced to a greater extent by metronidazole plus fleroxacin than by clindamycin plus fleroxacin, although differences were not always significant. Metronidazole plus fleroxacin was at least as active a clindamycin plus gentamicin against all species and was significantly more active against Clostridium spp. No regimen effectively eradicated enterococci from the abscesses. These results suggest that the addition of either metronidazole or clindamycin would effectively enhance the spectrum of fleroxacin for treatment of mixed aerobic and anaerobic infections.     

Legal rights of veterinarians under veterinary Good Samaritan statutes and equine liability statutes

OBJECTIVE: To determine the prevalence and clinical features of Candida species in hospital-acquired urinary tract infections (UTI) in a neonatal intensive care unit. DESIGN: A retrospective study was conducted of hospital-acquired UTI occurring in infants admitted to a neonatal intensive care unit between January 1, 1989, and June 30, 1995. Hospital-acquired infection was defined as one occurring in an infant who was at least 7 days of age and hospitalized since birth. Urinary tract infection was defined by a urine culture yielding a single organism with > 1000 colony-forming units/ml from a suprapubic aspiration or > 10,000 colony-forming units/ml via urethral catheterization. RESULTS: Fifty-seven infants had 60 UTI during the study period. Candida spp. were responsible for 25 of 60 (42%) UTI. The median gestational age of infants with candidal UTI was 26 weeks (range, 23 to 37) which was significantly less than that for infants with bacterial UTI, 28 weeks (range, 23 to 40) (P = 0.04). Candidemia was present in 13 of 25 (52%) candidal UTI which was significantly more often than bacteremia with bacterial UTI, 3 of 35 (8%) (odds ratio, 11.6; 95% confidence interval, 2.8 to 47.8). The median age of infection for candidal UTI was 34 days (range, 9 to 228), which was significantly earlier than for bacterial UTI, 79 days (range, 7 to 247) (P = 0.003). Renal pelvis fungus balls were present in 7 of 20 (35%) infants with candidal UTI who had renal ultrasound studies. CONCLUSIONS: Candida spp. were the pathogens identified in 42% of hospital-acquired urinary tract infections in a neonatal intensive care unit. Candidemia was associated with 52% of candidal UTI and bacteremia with 8% of bacterial UTI. Candidal UTI occurred significantly earlier than bacterial UTI. Renal fungus balls were present in 35% of infants with candidal UTI.     

The risk of infection associated with intra-arterial catheters for cancer chemotherapy

OBJECTIVE: To determine the frequency of, and risk factors for, infections associated with intra-arterial catheters used for cancer chemotherapy. METHODS: Between September 1992 and September 1995, we conducted a surveillance study of all 807 intra-arterial catheters placed for chemotherapy at our center. The insertion site was disinfected with povidone iodine and alcohol, and the arterial catheter was placed using maximal sterile barrier precautions. Upon removal, all intravascular segments were submitted for semi-quantitative culture. RESULTS: No episodes of catheter-related bloodstream infection (95% confidence interval [CI95], 0%-1.6%) were observed. However, the risk of colonization (>15 colony-forming units) of arterial catheters was 15% (CI95, 12%-17%). Retrospective risk-factor analysis conducted on 224 intra-arterial catheters placed for chemotherapy in 1993 showed that colonization was associated significantly with duration of catheterization (median of 1 day for culture-negative catheters vs median of 4 days for culture-positive catheters, P<.001). Age, gender, prior radiotherapy, underlying cancer, neutropenia, and hypoalbuminemia were not associated with catheter colonization. CONCLUSION: Intra-arterial catheters for cancer chemotherapy placed under maximal sterile barrier precautions for a short period of time are associated with a very low risk of bloodstream infection.     

Mechanomyography and oxygen consumption during incremental cycle ergometry

Brucella abortus strain RB51 was recently approved as an official brucellosis calfhood vaccine for cattle by the Animal and Plant Health Inspection Service branch of the United States Department of Agriculture. Currently available serologic surveillance tests for B. abortus do not detect seroconversion following SRB51 vaccination. The purpose of this study was to evaluate a dot-blot assay using gamma-irradiated strain RB51 bacteria for its specificity and sensitivity to detect antibody responses of cattle vaccinated with strain RB51. Dot-blot titers of sera at a recommended dosage (10(10) colony-forming units) were similar to those of sera from cattle vaccinated with similar numbers of B. abortus strain 19 and greater (P < 0.05) than titers of nonvaccinated cattle. In the first 12 weeks after vaccination with 10(10) colony-forming units of strain RB51, the RB51 dot-blot assay had 100% specificity for titers of 80 or less and a 53% sensitivity for titers of 160 or greater. Sensitivity of the RB51 dot-blot assay peaked at 4 weeks after vaccination with 10(10) colony-forming units of strain RB51. Dot-blot responses of sera from cattle vaccinated with a reduced dosage of strain RB51 (10(9) colony-forming units) did not differ (P > 0.05) from titers of sera from nonvaccinated cattle. Following intraconjunctival challenge with B. abortus strain 2308, titers on the RB51 dot-blot assay did not differ (P > 0.05) between nonvaccinated cattle and cattle vaccinated at calfhood with strain 19 or strain RB51.     

Respiratory infection in lipid-fed rabbits enhances sudanophilia and the expression of VCAM-1

The pathogenesis of atherosclerosis has been related to infection of the arterial wall, but it is not clear whether this occurs before or after the development of lipid-containing lesions. Respiratory bacterial infection increases the expression of vascular cell adhesion molecule-1 (VCAM-1). We therefore examined whether a similar infection would enhance atherosclerosis in New Zealand White rabbits fed chow supplemented by 15% (w/w) egg yolk for 50 days. Rabbits with naturally acquired respiratory infection by Pasteurella multocida, pathogen-free (SPF) animals infected by P. multocida in the laboratory, and age-matched SPF rabbits maintained in a disease-free environment were used. Endothelial cells expressing VCAM-1 in the aorta between intercostal arteries 3 and 5 were identified using anti-VCAM-1 (Rb1/9) and an alkaline-phosphatase-linked secondary antibody and quantified in H?utchen preparations. The remainder of the aorta was stained with Sudan IV to show lipid deposition. The expression of VCAM-1 (mean +/- SEM per 10,000 cells) was 22 +/- 8 (n = 5) in the lipid-fed SPF rabbits, significantly different from that in the lipid-fed rabbits with naturally occurring infection (190 +/- 51 (n = 5)) or from rabbits infected in the laboratory (106 +/- 25 (n = 5)). The extent of Sudanophilia was significantly greater in the naturally infected rabbits (8.3 +/- 1.2%) or infected SPF rabbits (10.3 +/- 1.8%) than in the SPF rabbits (2.7 +/- 0.8%; P < 0.05). Antibiotic treatment in naturally infected rabbits reduced the number of cells expressing VCAM-1 and the extent of the Sudanophilia to baseline levels. Thus, Sudanophilia is enhanced by bacterial infection in rabbits fed egg yolk and is associated with a significant increase in VCAM-1.     

In vitro efficacy of antimicrobial-coated bladder catheters in inhibiting bacterial migration along catheter surface

Most cases of catheter-related urinary tract infection are probably caused by organisms that migrate from the urethral meatus-catheter interface along the external surface of the catheter into the bladder. To examine the ability of bladder catheters coated with minocycline and rifampin to inhibit bacterial migration along the external surface of the catheter, a novel in vitro bladder model was used. Compared with uncoated catheters, antimicrobial-coated bladder catheters significantly impeded the migration of Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterococcus faecalis, and Candida albicans (bacteriuria developed at a mean of 2-5 days vs. 9-34 days, respectively, after bacterial contamination of the catheter). Although production of zones of inhibition by coated catheters may provide some protection against infection, there was no correlation between the size of zones of inhibition and level of efficacy in inhibiting bacterial migration in vitro. Examination of the clinical efficacy of these antimicrobial-coated bladder catheters is prudent.     

Filling hemodialysis catheters in the interdialytic period: heparin versus citrate versus polygeline: a prospective randomized study

Heparin and saline are commonly used to fill hemodialysis central venous catheters to prevent their thrombosis during the interdialytic period. The purpose of this prospective clinical study was to evaluate whether replacing heparin with citrate or polygeline could ensure satisfactory catheter function without exposing patients to the risk of systemic heparinization. Thirty end-stage renal disease (ESRD) patients with subclavian or jugular single lumen catheters as temporary vascular access for hemodialysis were enrolled. After the insertion of the catheters, the patients were randomly assigned to one of the following three filling groups: Group A, heparin; Group B, citrate; Group C, polygeline. Before each dialysis, the filling solution was aspirated and clot volume, if present, was measured. The catheter usage time and the clot volume were 23 +/- 24 days and 0.052 +/- 0.035 ml in Group A, 51 +/- 36 days and 0.059 +/- 0.032 ml in Group B, and 32 +/- 10 days and 0.056 +/- 0.038 ml in Group C, respectively. Our results indicate that citrate or polygeline can replace heparin effectively as a filling solution for single lumen temporary hemodialysis catheters.     

Genus-specific biochemical markers for Phytomonas spp

In a newly established murine model of chronic Pseudomonas aeruginosa respiratory infection mimicking diffuse panbronchiolitis (DPB), we investigated the effect of oral administration of clarithromycin on lymphocyte accumulation in the lung. Infection was produced by placement of a plastic tube precoated with P. aeruginosa in the bronchus. The number of bacteria on the tube was 6.25 +/- 0.22 log10 colony-forming units (cfu)/ml. Viable bacteria were constantly isolated at 10(5) to 10(6) cfu/specimen from the lungs for more than 1 yr. The histopathologic features resembled those of DPB consisting of massive accumulation of lymphocytes in the lung. The total number of pulmonary lymphocytes started to increase on Day 7, reaching a peak level within 12 d of intratracheal challenge. The number remained steady at that level for up to 120 d. There was also a steady fall in the CD4+/CD8+ ratio in the lungs, commencing on Day 7 and persisting to Day 120. A 10-d course of oral clarithromycin (10 mg/kg/d) from Day 7 resulted in a reduction of lymphocyte numbers to baseline level, although the dose did not influence the number of bacteria in the lungs. Treatment also increased the CD4+/CD8+ ratio to the baseline level from Day 7 to 17. Our results were similar to those detected in bronchoalveolar lavage fluid of patients with DPB and suggest that the therapeutic benefits of clarithromycin are due to its anti-inflammatory properties rather than antimicrobial effect.     

Correlates of alcohol use among methadone patients

A combination of low-dose penicillin (75,000 IU/kg twice daily [b.i.d.]) vancomycin (30 mg/kg b.i.d.) and gentamicin (6 mg/kg b.i.d.) has been shown to be as effective as a combination of high-dose penicillin (500,000 IU/kg b.i.d.) and gentamicin (6 mg/kg b.i.d.) in the treatment of rabbit endocarditis caused by an Enterococcus faecium strain moderately resistant to beta-lactams and highly resistant to glycopeptides. The same regimens were evaluated against an E. faecium strain highly resistant to both penicillin (MIC, 128 micrograms/mL) and vancomycin (MIC, 512 micrograms/mL). High doses of penicillin-gentamicin and vancomycin-gentamicin had no effect in in vitro killing-curve studies or in rabbits after treatment for 5 days. High doses of penicillin-vancomycin were only bacteriostatic in killing curves and provided a small reduction in the bacterial titers of the vegetations. In contrast, high-dose penicillin-vancomycin-gentamicin was bactericidal in vitro and highly effective in treating rabbits. However, the emergence of a bacterial subpopulation resistant to the synergistic effect of penicillin and vancomycin could reduce the clinical utility of this combination.     

Candida endocarditis in the first year of life

Candida is an increasing problem as a causal agent of nosocomial infection in neonates and infants. We report 15 cases of infective endocarditis caused by Candida spp treated at the Hospital Infantil de Mexico between 1980 and 1991. The diagnosis of endocarditis was established by the identification of Candida in at least two blood cultures and echocardiographic assessment. From 110 cases of systemic candidiasis during the eleven years period of study, fifteen patients presented endocarditis (13.6%), all had a central venous catheter. Three had antecedent of congenital heart disease. Candida isolation was obtained an average of 28 days after admission. The major clinical findings were: fever in 13 patients, respiratory distress and cardiac murmurs observed in nine respectively. Thrombocytopenia was present in eight children. The echocardiographic evaluation showed vegetations located in the superior vena cava in six, right atrium in five, tricuspid valve in two, inferior vena cava and right ventricle in one respectively. Three cases were subjected to surgical treatment. Nine patients died for a case fatality rate of 60%. The echocardiographic evaluation practiced in all patients with suspicion of systemic candidiasis is critical for the prognosis. The identification of endocardiac involvement coupled with the opportune administration of antifungal therapy and surgical treatment may improved the survival.     

Central venous catheters in patients with AIDS

Central venous catheters (CVCs) for patients with AIDS are at risk of a number of complications including bacterial infections. A 6-year retrospective review was undertaken of the records of the 33 patients (42% infected by injection drug use (IDU)) who received intravenous therapy both in hospital and at home via CVCs. Twenty-eight per cent of 53 insertions suffered a complication, the commonest of which was a pneumothorax (8%). The post insertion complication rate was 0.98/100 catheter days (cd). Thrombotic occlusion (0.15/100 cd) was the commonest non septic event while sepsis was overall the commonest event (0.69/ 100 cd) of which half were considered serious (0.33/100 cd). The most frequently isolated organisms were Staphylococci spp. (71%). The median time to an exit site infection was 59 days and to serious catheter sepsis 86 days. Infection did not differ significantly with age, gender, transmission risk activity or catheter type although Portacaths had the lowest rate of infection (0.33/100 cd). The median survival of the 53 CVCs was 88 days although if the temporary catheters were excluded it was 118 days. Kaplan-Meier estimates of survival analysis revealed 55%, 32% and 19% of all the CVCs surviving 3, 6 and 12 months respectively. Our experience suggests that home intravenous therapy and previous IDU does not preclude the use of CVCs although further research is needed on reducing the infection-related complications of such therapy.     

Proteolytic processing of ricin A chain is not required for cytotoxicity

PURPOSE: To evaluate prospectively the use of peripherally inserted central catheters in a large pediatric population. MATERIALS AND METHODS: During a 3-year period, data were collected prospectively on 523 consecutive attempts to place peripherally inserted central catheters in children. Patients underwent radiologically guided placement because attempts were unsuccessful on the inpatient units or a patient request was made. Fluoroscopy with use of contrast material and venography were used to place catheters and document the position of the catheter tip. Follow-up data were collected until treatment cessation or catheter removal. RESULTS: Among 523 attempts, 486 (92.9%) catheters were successfully placed. In the 37 (7.1%) unsuccessful cases, more than half of these children were younger than 24 months of age or weighed less than 5 kg. Ages of patients in whom 523 placement attempts were made ranged from 3 weeks to 18 years (mean, 6.9 years). Catheters were in place from 1 to 390 days (mean, 20 days). Frequency of infection was 1.9% (nine cases); incidence of infection was 0.93 per 1,000 catheter-placement days. There were two cases (0.4%) of central venous thrombosis. Most patients were discharged within 2 days of catheter placement. CONCLUSION: Fluoroscopically guided placement of peripherally inserted central catheters is a safe and effective method for establishing intermediate- and long-term central venous access in the pediatric population.     

Comparative experience of a simple technique for laparoscopic chronic ambulatory peritoneal dialysis catheter placement

BACKGROUND: Chronic ambulatory peritoneal dialysis (CAPD) is now an established technique for renal dialysis. Patients with renal failure cope poorly with major surgery and it is vital that the dialysis catheter tip is sited accurately in the pelvis if long-term catheter function is to be achieved. Laparoscopic placement of CAPD catheters may have potential advantages for renal patients by avoiding the morbidity of a laparotomy. METHODS: A retrospective audit was performed of all CAPD catheters inserted at the John Hunter Hospital over a 2-year period. Results of laparoscopically inserted catheters and those placed at laparotomy were compared. RESULTS: Sixty catheters were inserted, 30 laparoscopically and 30 at laparotomy. The mean operative time was 41 min in the laparoscopic patients and 57 min in the laparotomy patients (P = 0.0001). The mean total dose of narcotic administered postoperatively was significantly less in the laparoscopic group (5 mg vs 65 mg, P = 0.00002). There were three minor peri-operative complications in the laparoscopic group and seven peri-operative complications in the laparotomy group, three required reoperation and one resulted in the patient's death. There were no significant differences in the incidence of exit-site infection, catheter blockage, peritonitis, and overall catheter survival, although the laparoscopically placed catheters had been followed up for a shorter period (10 vs 16 months). CONCLUSIONS: This laparoscopic technique is safe and effective. Postoperative pain was less than for open placement. Laparoscopically placed catheters had a low incidence of peri-operative complications. Medium-term patency is similar to conventionally placed catheters. This procedure requires no additional equipment to that available for laparoscopic cholecystectomy and takes less time than the open operation.     

In vivo efficacies of quinolones and clindamycin for treatment of infections with Bacteroides fragilis and/or Escherichia coli in mice: correlation with in vitro susceptibilities

Therapy with ofloxacin, ciprofloxacin, and lomefloxacin (alone or in combination with clindamycin) and therapy with sparfloxacin, clinafloxacin, and temafloxacin alone were given to mice with subcutaneous abscesses. The abscesses were caused by two Bacteroides fragilis isolates, one of which was susceptible and one of which was resistant to ofloxacin, ciprofloxacin, and lomefloxacin, alone or in combination with Escherichia coli. The abscesses were examined 5 days after inoculation. Numbers of B. fragilis organisms reached log10 10.2 to 11.8 per abscess, and numbers of E. coli organisms reached log10 10.6 to 11.8 per abscess. All of the quinolones reduced the number of susceptible B. fragilis isolates (log10 3.6 to 6.9) and E. coli isolates (log10 5.7 to 6.8). However, ciprofloxacin and lomefloxacin failed to reduce the number of resistant B. fragilis organisms in single-organism or mixed infections. The addition of clindamycin to either ofloxacin, ciprofloxacin, or lomefloxacin reduced the numbers of both susceptible and resistant B. fragilis organisms (log10 3.8 to 7.8). In contrast, sparfloxacin, clinafloxacin, and temafloxacin were effective as single therapy in eradicating B. fragilis resistant to ofloxacin, ciprofloxacin, and lomefloxacin. These in vivo data confirm the in vitro activity of these quinolones and suggest that although ofloxacin, ciprofloxacin, and lomefloxacin are occasionally effective as single agents in eradicating mixed infection by susceptible strains of B. fragilis and E. coli, addition of an agent with activity against anaerobic organisms will ensure their efficacy. Quinolones with good efficacy against B. fragilis may be effective as single-agent therapy of mixed infections.     

Specific features of nosocomial infections in the elderly at a general hospital center. 5 surveys of annual prevalence

Specific features of nosocomial infections in patients aged 70 years or older admitted to a short-term care medical department in a 400-bed general hospital were studied to assist in designing nosocomial infection control programs for this population. Data from five annual prevalence surveys were evaluated retrospectively. The 517 patients aged 70 years or older were compared to the 1093 patients younger than 70 years. The older patients were more likely to have risk factors for nosocomial infections including severe disease (36.2% vs 19.1%; P < 10(-6)), referral from another department (24.6% vs 17.5%; P < 0.01), a long hospital stay duration (8.5 days vs 3.5 days), mechanical ventilation (4.3% vs 1.6%; P < 0.01), an indwelling urinary catheter (12.0% vs 4.0%; P < 10(-7)), and a long median duration of urinary catheterization (6 days vs 2 days). The prevalence of nosocomial infections was increased nearly two-fold in the older patients (10.3% vs 5.6%; P < 0.01), although the difference was statistically significant only for urinary tract infections (5.4% vs 1.4%; P < 10(-5)), particularly in patients without urinary catheters. After exclusion of all patients with urinary tract infections, the prevalence of nosocomial infections was similar in the older and younger patients (4.3% vs 3.7%) despite a persistently higher frequency of risk factors for nosocomial infection in the older group. These results indicate that urinary tract infection should be the main target of programs aimed at minimizing nosocomial infection in elderly patients admitted to short-term care facilities. Faultless technique is essential during urinary catheter insertion. High-quality nursing care contributes substantially to the prevention of urinary tract infection in noncatheterized patients with urinary incontinence or neurologic disorders.     

Imaging experimental infective endocarditis with indium-111-labeled blood cellular components

The capability of radionuclide imaging to detect experimental aortic valve infective endocarditis was assessed with indium-111 (111In)-labeled blood cells. Sequential cardiac imaging and tissue distribution studies were obtained in 17 rabbits with infective endocarditis after administration of 111In-platelets and in five after 111In-polymorphonuclear leukocytes. Forty-eight to 72 hours after platelet administration, in vivo imaging demonstrated abnormal 111In uptake in all animals in the region of the aortic valve in an anatomically distinct pattern. Images of the excised heart showed discrete cardiac uptake conforming to the in vivo image and gross pathological examination. 111In platelet uptake in vegetations from the 17 animals averaged 240 +/- 41 times greater than that in normal myocardium and 99 +/- 15 times greater uptake in blood. In contrast, 111In-leukocyte cardiac imaging showed no abnormal aortic valve uptake 24 hours after tracer administration and the lesion myocardium activity ratio was only 5 +/- 2 (3 +/- 1 for lesion/blood activity). Four normal rabbits demonstrated neither positive 111In platelet scintigraphs nor abnormal cardiac tissue uptake. Likewise, noncellular 111In was not concentrated to any significant extent in three animals with infective endocarditis. This study demonstrates that 111In platelet, but not leukocyte cardiac imaging, is a sensitive technique for detecting experimental infective endocarditis. The imaging data conform to the cellular pathology of the infective endocarditis vegetation.     

Characteristics of murine model of genital infection with Chlamydia trachomatis and effects of therapy with tetracyclines, amoxicillin-clavulanic acid, or azithromycin

Following intravaginal inoculation of progesterone-treated outbred mice with Chlamydia trachomatis MoPn, 4 to 6 log10 inclusion-forming units were recovered in vaginal swabs for 21 days but all animals were culture negative after 28 days. Serum antibody titers were elevated and remained high for at least 70 days. Between 28 and 70 days, upper tract infection (inflammation and distension of the uterine horns, occlusion of oviducts with inflammatory exudate, pyosalpinx, and hydrosalpinx) was seen in > 80% of the animals. Mice were dosed orally, commencing at 7 days after infection, with minocycline, doxycycline, or amoxicillin-clavulanate. Further groups received azithromycin either as a single high dose or as lower once-daily doses. In addition, minocycline and amoxicillin-clavulanate were administered at 24 h after infection, and this early treatment prevented elevation of antibody titers whereas delayed therapy did not. Vaginal swabs from mice in all treatment regimens were culture negative except for 25% of mice receiving either early amoxicillin-clavulanate or low-dose azithromycin, which yielded low numbers (20 to 70 inclusion-forming units) of chlamydiae. Numbers of fertile mice in the early treatment regimens and their litter sizes were similar to those of noninfected controls, although 25% of amoxicillin-clavulanate-treated mice had unilateral hydrosalpinges. In comparison, 88% of untreated mice developed hydrosalpinges and only 25% conceived. Delayed dosing did not affect the outcome of amoxicillin-clavulanate therapy but did diminish the protective efficacy of minocycline such that 50% of treated mice had either unilateral hydrosalpinges or ovarian abscesses. Doxycycline and azithromycin were highly effective in restoring fertility. This model makes possible the study of both short- and long-term outcomes of chlamydial infection.     

In vitro and in vivo efficacy of a rifampin-loaded silicone catheter for the prevention of CSF shunt infections

Infection of cerebrospinal fluid (CSF) shunts is one of the major complications associated with their use and is usually managed by shunt removal, temporary insertion of an external drainage and implantation of a new shunt system. We have evaluated the efficacy of a rifampin-loaded silicone ventricular catheter to prevent bacterial colonization and infection in vitro and in an animal model. On the basis of an incorporation process a rifampin-loaded catheter was developed which is capable of releasing rifampin in bacteriocidal concentrations for 60 days and more. In a stationary bacterial adherence assay using S. epidermidis as test strain, the colonization resistance of the device was demonstrated. To assess the capability of the catheter to prevent CSF shunt infections, a rabbit model was developed which allowed the establishment of a reliable and reproducible CSF infection by implantation of silicone catheters into the ventricle and inoculating S. epidermidis (minimal dose 10(6) cfu) or S. aureus (minimal dose 10(3) cfu). Rifampin-loaded catheters (12 animals inoculated with S. epidermidis, 8 animals inoculated with S. aureus) were compared with non-loaded (14 animals inoculated with S. epidermidis, 19 animals inoculated with S. aureus) control catheters, and infection was documented by clinical, microbiological and histological methods. In contrast to the control group, none of the animals with rifampin-loaded catheters showed clinical signs of infection. Furthermore, in none of the materials obtained after sacrifice of the animals (catheter, brain tissue, CSF, blood) could the infecting bacteria be cultured, whereas in materials from animals with the unloaded catheter the infecting strains could always be cultured from the catheter and from surrounding brain tissue. The histological examination of catheter-adjacent tissue supported these findings. We conclude that a rifampin-loaded silicone ventricular catheter is capable of completely preventing bacterial colonization and infection by staphylococci as the main causative organisms in CSF shunt infections and should be further evaluated in clinical trials.     

Catheter infection in intensive care: influence of systematic replacement of central venous catheters on a guide wire every 4 days

OBJECTIVES: Determine whether systematic replacement of central venous catheters on a guide wire every 4 days leads to a lower rate of catheter infection. METHODS: We conducted a prospective randomized study comparing systematic catheter replacement with the standard procedure where one-way catheters are left in situ as needed. RESULTS: The study included 150 patients and 170 catheters. Catheter replacement on a guide wire was performed 169 times. The rate of infection was not significantly different between the group of patients with replacement (3.7 for 1000 catheter days) and the group with systematic replacement (5.4 for 1000 catheter days). No mechanical complications occurred during the replacement procedures on guide wires. CONCLUSION: We do not recommend systematically replacing catheters on a guide wire for the prevention of catheter infection. This procedure may however be indicated in case of suspected catheter infection as no mechanical of infectious complications occurred.