Bioequivalence study of rabeprazole sodium on healthy human volunteers.

The newly developed proton pump inhibitor rabeprazole sodium is expected to have beneficial effects in the treatment of peptic ulcer. The pharmacokinetic parameters (C(max), AUC(o-t), t(max)) of this drug have been evaluated to compare the single dose (20 mg) bioavailability of rabeprazole sodium with the standard reference. High performance liquid chromatography (HPLC) coupled with UV detector set at 280 nm has been used to determine plasma concentration of 12 human volunteers as per Drugs Controller General of India (DCGI) guidelines. The method has been validated over a linear range of 20-480 ng/ml from plasma. The minimum quantifiable concentration was set at 10 ng/ml [co-efficient of variance (CV) < 10%]. By comparing AUC(o-t) the relative bioavailability of test preparation has been found to be 100.88% of that of reference preparation.

A study to determine the pharmacokinetics of gatifloxacin following a single oral dose.

Gatifloxacin is a broad spectrum fluoroquinolone that offers enhanced Gram-positive activity and anaerobic coverage to other fluoroquinolones. The pharmacokinetic parameters (Cmax, AUCo-t, tmax) of this drug have been evaluated to compare the single dose (400mg) bioavailability of gatifloxacin with the reference formulation. High performance liquid chromatography (HPLC) coupled with U-V detector set at 290 nm has been used to determine plasma concentration of 12 human volunteers as per DCGI (Drug Controller General of India) guidelines. The method has been validated over a linear range of 0.25 to 8 microg/ml from plasma. The minimum quantifiable concentration has been set at 0.25 microg/ml (% CV < 10%). The pharmacokinetic parameters are: Cmax = 4.366 +/- 0.44 microg/ml at tmax = 1.83 +/- 0.44 hour, AUCO0-t = 25.26 +/- 2.91 microg hour/ml, AUCo-inf = 33.68 +/- 4.31 microg hour/ml, Kel = 0.094 +/- 0.024/hour and t1/2 = 8.0 +/- 1.92 hour.

Cross-sectional study of consumption, compliance and awareness about antibiotic utilisation amongst the urban community in Kolkata.

A cross-sectional survey was conducted upon 500 respondents, comprising of 250 adults and 250 children who did consume antibiotics in the previous three months. Data were analysed to determine the patterns of utilisation, compliance and awareness regarding antibiotic medication amongst a selected urban population at Kolkata. Antibiotic consumption without prescription was evident amongst 41.2% of adults in comparison to that of 8.4% in children (P < 0.01). Compliance to daily dosage was observed in 40.8% of adults in comparison to 82.8% in children (P < 0.01). Awareness pattern regarding antibiotics were reported to have been more in the children group (16.4%) while compared to the adults (8%). The knowledge regarding antibiotic resistance remained more or less similar in both the groups. The study concludes that high over the counter (OTC) sale and inadequate compliance to antibitotic medication needs further intervention approach towards information, education and communication (IEC) to all concerned.

High performance liquid chromatographic determination of cox-2 inhibitor rofecoxib in human plasma.

A convenient, sensitive and simple method for the determination of rofecoxib in human plasma is presented. The analytical technique is based on reversed phase high performance liquid chromatography coupled with UV detector (Knauer, Germany) set at 272 nm. The retention time of rofecoxib after recovery from plasma, was 8.9 minutes. The method has been validated over a linear range of 50-450 ng/ml from plasma. After validation the method was used to study the pharmacokinetic profile of rofecoxib in 6 healthy volunteers as per DCGI guidelines after administration of a single oral dose (50 mg). The extraction efficiency from plasma varied from 93.95-99.58%. The minimum quantifiable concentration was set at 50 ng/ml (% CV < 10%). The pharmacokinetic parameters were Cmax = 318.58 +/- 30.65 ng/ml at tmax = 2.66 +/- 0.25 hours, AUC0-t = 4007.88 +/- 438.32 ng hour/ml, AUC0-yen = 5454.66 +/- 822.29 ng hour/ml, Kel = 0.0433 +/- 0.0067/hour, and t1/2 = 16.36 +/- 2.89 hours.

Birds disperse ixodid (Acari: Ixodidae) and Borrelia burgdorferi-infected ticks in Canada.

A total of 152 ixodid ticks (Acari: Ixodidae) consisting of nine species was collected from 82 passerine birds (33 species) in 14 locations in Canada from 1996 to 2000. The Lyme disease spirochete Borrelia burgdorferi Johnson, Schmidt, Hyde, Steigerwaldt & Brenner was cultured from the nymph of a blacklegged tick, Ixodes scapularis Say, that had been removed from a common yellowthroat, Geothlypis trichas L., from Bon Portage Island, Nova Scotia. As a result of bird movement, a nymphal I. scapularis removed from a Swainson's thrush, Catharus ustulatus incanus (Godfrey), at Slave Lake, Alberta, during spring migration becomes the new, most western and northern record of this tick species in Canada. Amblyomma longirostre Koch, Amblyomma sabanerae Stoll, and Ixodes baergi Cooley & Kohls are reported for the first time in Canada. Similarly, Amblyomma americanum L., Arnblyomma maculatum Koch, and ixodes muris Bishopp & Smith are reported for the first time on birds in Canada. After removal of an I. muris gravid female from a song sparrow, Melospiza melodia Wilson, at St. Andrews, New Brunswick, eggs were laid, which developed into larvae, and this new tick-host record demonstrates that birds have the potential to start a new tick population. We conclude that passerine birds disperse several species of ixodid ticks in Canada, and during spring migration translocate ticks from the United States, and Central and South America, some of which are infected with B. burgdorferi.

Serratia marcescens transmission in a pediatric intensive care unit: a multifactorial occurrence.

BACKGROUND: Fourteen patients in the pediatric cardiac intensive care unit (CICU) had > or =1 positive culture for a single strain of Serratia marcescens from April through December 1995 (study period). OBJECTIVES: To identify risk factors for S marcescens infection or colonization in a pediatric CICU. METHODS: Retrospective case-control study. Assessment of CICU infection control practices and patient exposure to CICU health care workers (HCWs). Epidemiologic-directed cultures of the environment and HCWs' hands were obtained. SETTING: Pediatric CICU. PATIENTS: Fourteen patients in the pediatric CICU had > or =1 positive culture for a single strain of S marcescens from April through December 1995 (study period). CICU patients who did not have S marcescens infection or colonization during the study period were randomly selected as controls. RESULTS: A case patient was more likely than a noncase patient to have exposure to a single HCW (odds ratio [OR], 19.5; 95% CI, 2.6-416; P<.003); however, this association was not adequately explained by epidemiologic or microbiologic studies. Interviews suggested that during the outbreak period, handwashing frequency among HCWs might have been reduced because of severe hand dermatitis. CONCLUSIONS: A combination of factors, including breaks in aseptic technique, reduced frequency of handwashing among HCWs before and between caring for patients, decreased attention to infection control practices, and environmental contamination may have indirectly contributed to this S marcescens infections outbreak.

Transfusion-transmitted bacterial infection in the United States, 1998 through 2000.

BACKGROUND: Bacterial contamination of blood components can result in transfusion-transmitted infection, but the risk is not established. STUDY DESIGN AND METHODS: Suspected cases of transfusion-transmitted bacteremia were reported to the CDC by participating blood collection facilities and transfusion services affiliated with the American Red Cross, AABB, or Department of Defense blood programs from 1998 through 2000. A case was defined as any transfusion reaction meeting clinical criteria in which the same organism species was cultured from a blood component and from recipient blood, with the organism pair confirmed as identical by molecular typing. RESULTS: There were 34 cases and 9 deaths. The rate of transfusion-transmitted bacteremia (in events/million units) was 9.98 for single-donor platelets, 10.64 for pooled platelets, and 0.21 for RBC units; for fatal reactions, the rates were 1.94, 2.22, and 0.13, respectively. Patients at greatest risk for death received components containing gram-negative organisms (OR, 7.5; 95% CI, 1.3-64.2; p = 0.009). CONCLUSION: Bacterial contamination of blood is an important cause of transfusion-transmitted infection; infection risk from platelet transfusion is higher compared with that from RBCs, and, overall, the risk of infection from bacterial contamination now may exceed that from viral agents. Recipients of components containing gram-negative organisms are at highest risk for transfusion-related death. The results of this study may help direct efforts to improve transfusion-related patient safety.

One program's experience of OSCE vs. written board certification results: a pilot study.

The objective structured clinical examination (OSCE) has been the focus of a lot debate with respect to reliability and validity. Much of the controversy surrounding these components lies in a lack of comparison with a "gold standard." Further work is needed to improve the evaluation of clinical skills to the point that a gold standard can truly be said to exist.

Risk factors for acquisition of vancomycin-resistant enterococci among patients on a renal ward during a community hospital outbreak.

BACKGROUND: During an outbreak of vancomycin-resistant enterococcal (VRE) infection and colonization at a community hospital in Indianapolis, Indiana, we performed a case-control study of patients on the hospital's renal unit to determine risk factors for acquisition of VRE among this potentially high-risk patient population. METHODS: Twenty-four renal patients with VRE colonization/infection (ie, case-patients) were compared by univariate and multivariate analyses with 29 renal patients with nosocomially acquired vancomycin-susceptible enterococcal infection and colonization (ie, controls). RESULTS: Age and length of hospitalization were similar between the VRE case-patients and the vancomycin-susceptible enterococcal control-patients, but case-patients had higher Acute Physiology and Chronic Health Evaluation II scores and received significantly greater numbers of antimicrobials and significantly more days of antimicrobials during the 60 days preceding the first positive enterococcal culture. In an assessment of the appropriateness of vancomycin use, one third of vancomycin orders were found to be inappropriate in both patient groups. CONCLUSIONS: Our data show that among renal patients, those who are severely ill and receive multiple and prolonged courses of antimicrobials are at greatest risk for acquiring VRE infection or colonization. The Centers for Disease Control and Prevention recommends that hospitals develop a comprehensive plan to prevent and control infection and colonization of patients with VRE. This plan should include prompt identification of affected patients, initiation of isolation precautions to prevent patient-to-patient transmission of VRE, and prudent use of antimicrobials, including vancomycin.

Association between implementation of CDC recommendations and ventilator-associated pneumonia at selected US hospitals.

BACKGROUND: To assess whether selected recommendations in the Centers for Disease Control and Prevention "Guideline for Prevention of Nosocomial Pneumonia" were being implemented and having an impact on the occurrence of ventilator-associated pneumonia (VAP) at US hospitals, we surveyed hospitals participating in the National Nosocomial Infections Surveillance (NNIS) system. METHODS: We mailed a questionnaire to the infection control practitioner of each NNIS hospital in 1995 and used data from the NNIS system to calculate annual rates of VAP. RESULTS: Of the 188 hospitals surveyed, 179 (95%) returned completed questionnaires. Of these, 175 (98%) had implemented the recommended change of mechanical-ventilator breathing circuits at 48-hour or greater intervals. Of 110 hospitals using the hygroscopic condenser-humidifiers or heat-moisture exchangers with ventilators, 102 (93%) changed the hygroscopic condenser-humidifiers or heat-moisture exchangers routinely, and of 98 hospitals using bubbling humidifiers, 96 (98%) used sterile water to fill these humidifiers. Other practices for which the guideline provides no recommendation and their frequency of use by NNIS hospitals include use of hygroscopic condenser-humidifiers or heat-moisture exchangers (110/179 [61%]) and use of bacterial filters in anesthesia machines (128/171 [61%]). There was a significant decrease in the VAP rate from 1987 to 1998. CONCLUSION: Most NNIS hospitals had implemented selected recommendations in the Centers for Disease Control and Prevention "Guideline for Prevention of Nosocomial Pneumonia" before the final publication of the revised guideline. Further studies are needed to assess the impact of these recommendations on the occurrence of VAP.

Seasonal variation of Acinetobacter infections: 1987-1996. Nosocomial Infections Surveillance System.

To determine whether nosocomial infections due to Acinetobacter species have increased over the past 10 years and whether infections continue to have a pronounced seasonal variation, we analyzed infections reported by hospitals in the National Nosocomial Infections Surveillance System that performed adult and pediatric intensive care unit surveillance from 1987 through 1996. Overall, 3447 nosocomial acinetobacter infections were reported during 5,596, 156 patient-days. There was a yearly median of 7.2 infections (range, 5.0-10.5) per 10,000 patient-days and a downward trend in the rate of acinetobacter infections overall (P<.05) and of 2 major types of infection (P<.05): bloodstream infections (yearly median, 1.6 per 10, 000 central venous catheter-days; range, 1.3-2.9) and pneumonia (yearly median, 7.6 per 10,000 ventilator-days; range, 6.5-12.0). Throughout this period, average rates were significantly higher during July-October than during November-June for acinetobacter infections overall (8.0 vs. 5.2; P<.01) and for bloodstream infections (2.0 vs. 1.2; P<.01) and pneumonia (9.7 vs. 6.6; P<.01).

Lobular carcinoma-in-situ within a fibroadenoma of the breast.

We present a case of an in-situ lobular carcinoma within an otherwise benign fibroadenoma in a 45-year-old woman.

Regional dissemination of vancomycin-resistant enterococci resulting from interfacility transfer of colonized patients.

During early 1997, the Siouxland District Health Department (SDHD; Sioux City, IA) reported an increased incidence of vancomycin-resistant enterococcal (VRE) isolates at area health care facilities. To determine the prevalence and risk factors for colonization with VRE strains at 32 health care facilities in the SDHD region, a prevalence survey and case-control study were performed. Of 2266 patients and residents, 1934 (85%) participated, and 40 (2.1%) were positive for (gastrointestinal) VRE colonization. The prevalence of VRE isolates was significantly higher in acute care facilities (ACFs) than in long-term care facilities (LTCFs) (10/152 [6.6%] vs. 30/1782 [1.7%]; odds ratio [OR], 4.1; 95% confidence interval [CI], 1.8-9.0). LTCF case patients were significantly more likely than controls to have been inpatients at any ACF (19/30 vs. 12/66; OR, 8.0; 95% CI, 2.7-23.8). Of 40 VRE isolates, 34 (85%) were a related strain. The predominant strain was present in all 12 LTCFs that had at least 1 case patient in each facility. Soon after the introduction of VRE isolates into this region, dissemination to multiple LTCFs resulted from resident transfer from ACFs to LTCFs.

Fever and human immunodeficiency virus infection as sentinels for emerging mycobacterial and fungal bloodstream infections in hospitalized patients >/=15 years old, Bangkok.

To determine the etiology of bloodstream infections (BSIs) in hospitalized patients >/=15 years old in Thailand, prospectively enrolled, consecutive febrile (>/=38 degrees C) patients were admitted to one hospital during February-April 1997. After a patient history was taken and a physical examination was performed, blood was obtained for comprehensive culture and human immunodeficiency virus (HIV) testing. Of 246 study patients, 119 (48%) had BSIs, and 182 (74%) were infected with HIV. The 2 most common pathogens were Cryptococcus neoformans and Mycobacterium tuberculosis (30 and 27 patients, respectively). HIV-positive patients were more likely than HIV-negative patients to have mycobacteremia (57/182 vs. 0/64, P<. 0001), fungemia (38/182 vs. 2/64, P<.001), or polymicrobial BSIs (19/182 vs. 0/64, P<.002). Clinical predictors of BSIs included HIV infection, chronic diarrhea, lymphadenopathy, or splenomegaly. Mortality was higher among patients with than those without BSIs (P<. 001). Cohort-based microbiologic studies are critically important to diagnose emerging pathogens and to develop algorithms for empirical treatment of BSIs in developing countries.

Bloodstream infection associated with needleless device use and the importance of infection-control practices in the home health care setting.

The influence of infection-control practices on bloodstream infection (BSI) risk was examined in a home health care setting in which three needleless devices were used consecutively. A case-control study and a retrospective cohort study were conducted. Risk factors for BSI included lower education level, younger age, having a central venous catheter (CVC) with multiple ports, or having a tunneled CVC. Among patients with a tunneled CVC, those at greatest risk had been allowed to shower rather than bathe and to get their exit site wet (P<.01). A high proportion (49%) of isolates were hydrophilic gram-negative bacteria, suggesting water sources of infection. In the cohort study, the BSI rate decreased as the frequency of changing the needleless device end cap increased from once weekly up to every 2 days, suggesting that the mechanism for BSI may involve contamination from the end cap. These findings may help to develop infection-control measures specific to home health care.

Line-associated bloodstream infections in pediatric intensive-care-unit patients associated with a needleless device and intermittent intravenous therapy.

OBJECTIVES: To determine risk factors for an increase in line-associated bloodstream infections (BSIs) in three pediatric intensive-care units at one hospital that recently had changed brands of needleless access device. DESIGN: Retrospective case-control studies; review of the units' infection control policies and procedures for accessing and replacing components of needleless access devices. SETTING: A community tertiary-care hospital's three pediatric intensive-care units. PATIENTS: Children in one of the three intensive-care units with a central venous catheter in place during January 1, 1995, through May 15, 1996, who developed laboratory-confirmed primary BSI. Children who had central venous catheters in place for >48 hours and who did not develop BSI were chosen randomly as controls. RESULTS: Eight patients met the case definition; they had 11 episodes of BSI. Multivariate analysis identified duration of catheterization and exposure to the IVAC first-generation needleless device as independent risk factors for BSI. Compared with patients from another pediatric intensive-care unit in which the IVAC device also was used but in which an increased BSI rate did not occur, patients from the unit with an increased BSI rate were more likely to receive intermittent (vs continuous) intravenous therapy through one or more lumens. In both units, the IVAC device valve component was replaced every 6 days, and the endcap used to cover the valve (when connected to an unused lumen) was replaced every 24 hours or after each access. The BSI rate returned to baseline after institution of a policy to replace the entire IVAC device, valve, and endcap every 24 hours. CONCLUSIONS: An increased risk of BSI was associated with use of the IVAC first-generation needleless device when replaced every 6 days. This increased risk may have been more pronounced in one pediatric intensive-care unit, because patients were more likely to receive intermittent intravenous therapy. Intermittent intravenous therapy or central venous catheter flushing practices may be important determinants of BSI risk.

Tick-borne relapsing fever in British Columbia, Canada: first isolation of Borrelia hermsii.

The spirochete that causes tick-borne relapsing fever, Borrelia hermsii, was isolated in pure culture during 1995 and 1996 from three acutely ill human patients infected in southern British Columbia, Canada. The geographic area of exposure is a known focus of this disease dating back to 1930 when the first case was recognized in a human. Analyses of plasmid DNA, protein profiles, and reactivity with a species-specific monoclonal antibody identified the new isolates of spirochetes as B. hermsii, all of which were most similar to an isolate of this spirochete from northern California described previously. These are the first reported isolates of B. hermsii from Canada.