Nosocomial infection and fatality in medical and surgical intensive care unit patients.

We prospectively studied 526 patients admitted to the medical intensive care unit (MICU) and 799 patients admitted to the surgical intensive care unit (SICU) at a municipal hospital over a 20-month period. Rates of nosocomial infection were higher in the SICU patients (31% vs 24%). The SICU patients had more urinary tract infections, bacteremias, and wound infections, and the MICU patients were older, had higher acute physiology scores on admission and were more often admitted with shock or coma. The SICU patients were more likely to have received prior antibiotic therapy and had significantly higher numbers of endotracheal tubes, arterial lines, central venous lines, and indwelling bladder catheters. Of the 23 variables univariately associated with nosocomial infection, only five remained significant after entry into step-wise regression models. The MICU patients had a higher fatality rate in the MICU than did the SICU patients (18% vs 10%), but the relative risk of a death following nosocomial infection was 3.5 for both groups. Thirty variables were significantly associated with hospital fatality; nine remained significant after analysis by stepwise logistic regression.

Seroprevalence of hepatitis B virus and delta agent in parenteral drug abusers. Immunogenicity of hepatitis B vaccine.

The seroprevalence of hepatitis B virus (HBV) markers and antibody to the delta agent (anti-delta) was determined for 112 parenteral drug abusers entering a methadone maintenance program. Markers of HBV infection were found in 87.5 percent of the group, and seropositivity was significantly associated with duration of drug abuse (p = 0.02). Antibody to the hepatitis B core antigen (anti-HBc) was present in all seropositive subjects; three (2.7 percent) were hepatitis B surface antigen-positive, and 16 (14.2 percent) had only anti-HBc. Five (10.6 percent) of 47 subjects with HBV markers had anti-delta. Anti-delta was more common in subjects who reported multiple symptomatic episodes of hepatitis (p = 0.02) and fewer than three daily drug injections (p = 0.05). Ten susceptible subjects received hepatitis B vaccine, and seroconversion rates at one, three, and six months were 20.0, 88.8, and 100 percent, respectively. The data indicate that hepatitis B vaccine is immunogenic in this population, and that anti-HBc is the optimal prevaccination screening test. Recent outbreaks of fulminant HBV and delta co-infection among drug abusers emphasize the need for early immunization in this group.

Hepatitis B exposure in emergency medical personnel. Prevalence of serologic markers and need for immunization.

To assess the occupational risk of hepatitis B infection in emergency medical personnel, a seroepidemiologic survey of 87 emergency medical technicians and paramedics was conducted. Serologic markers indicating exposure to hepatitis B virus were detected in 18 percent. The prevalence of markers was associated with race (p = 0.006), with a relative risk of 3.5 (95 percent confidence interval 1.42 to 8.63) for nonwhites. Seropositivity was not associated with age, sex, previous clinical hepatitis, or blood transfusion. There was a suggestion that duration of employment as an emergency medical technician was related to the prevalence of hepatitis B markers (p = 0.11). Efforts to control the risk of hepatitis B infection in this profession are complicated by unique problems with post-exposure prophylaxis and uncontrolled exposure to blood. Immunization with hepatitis B vaccine would be the optimal strategy to reduce infection in this high-risk occupation.

Two-stage tuberculin testing with control antigens in patients residing in two chronic disease hospitals.

We studied the prevalence of tuberculin reactivity and anergy in 360 elderly patients residing in two municipal chronic disease hospitals. Eighty-five (26%) of the 323 patients tested had a positive reaction to a stage 1 tuberculin test and 12 (6%) of the 207 stage 1 tuberculin-negative patients exhibited a booster response to a stage 2 tuberculin test. Thirty percent of the same 207 patients had no response to an anergy panel of skin test antigens that included candida, mumps, and trichophyton. Nonresponders to tuberculin and the anergy panel had significantly higher one-year mortality rates compared to responders (44 v 20%, P = 0.001). Tuberculin-positivity among the 770 employees working in these facilities was 43%; 12 (4%) had a booster response. A survey of 29 randomly selected long-term care facilities in the Boston area indicated that all had a policy for pre-employment screening of employees, but less than 50% had a policy for patients and only one institution used two-stage testing. Routine tuberculin testing is recommended for long-term care facilities and the two-stage method is preferable in institutions with adequate resources.

Serosurvey of human immunodeficiency virus, hepatitis B virus, and hepatitis C virus infection among hospital-based surgeons. Serosurvey Study Group.

BACKGROUND: Because occupational blood contact places health-care workers at risk for infection with bloodborne pathogens, we wanted to estimate the prevalence of infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) among hospital-based surgeons and correlate the results with occupational and nonoccupational risk factors. STUDY DESIGN: All surgeons in training or in practice in general surgery, obstetrics and gynecology, or orthopedics at 21 hospitals in moderate to high AIDS incidence areas were eligible to participate in a voluntary, anonymous serosurvey. Serum samples were tested for HIV antibody, for HCV antibody, and for markers of HBV infection: hepatitis B surface antigen, total antibody to hepatitis B core antigen, and antibody to hepatitis B surface antigen. RESULTS: Of 2,887 eligible surgeons, 770 (27 percent) participated in the study. One of 740 surgeons not reporting nonoccupational risk factors was HIV seropositive (0.14 percent, upper limit 95 percent confidence interval [CI] equals 0.64 percent). None of 20 participants reporting nonoccupational HIV risk factors and none of ten not responding to the question on nonoccupational risk factors were HIV positive. Of 129 (17 percent) participants with past or current HBV infection, three (0.4 percent) had chronic HBV infection; all were negative for hepatitis B e antigen. Risk factors for HBV infection included not receiving hepatitis B vaccine (odds ratio [OR] 14.7, 95 percent CI 8.3 to 26.0) and practicing surgery at least ten years (OR 2.2, 95 percent CI 1.3 to 3.8). Seven (0.9 percent) participants had anti-HCV. CONCLUSIONS: Although not necessarily generalizable to all surgeons in moderate to high AIDS incidence areas, these results do not indicate a high rate of previously undetected HIV infection among surgeons who trained or practiced in these areas, or both. Hepatitis B virus posed the highest risk of infection with a bloodborne pathogen, followed by HCV and HIV.

Survey of nonoccupational HIV postexposure prophylaxis in hospital emergency departments.

BACKGROUND: Nonoccupational HIV postexposure prophylaxis (nPEP) is being used in community settings, but little is known about practice patterns. This study examined the status of nPEP in Massachusetts emergency departments (EDs), community sites where nPEP is most likely to be practiced. METHODS: In June 1998, a mailed survey was sent to identified medical directors of the 78 hospital EDs statewide; 66 (85%) responded. RESULTS: Overall, 52% reported having patient requests for nPEP within the prior year. 15% (10 of 66) had established written nPEP protocols; 33% (22 of 66) indicated their protocols were informal and not written. Twenty-five EDs could estimate the number of nPEP patients assessed; their mean estimate was 31 for the prior year (standard deviation [SD], 19.9) and 34% of the patients overall had nPEP recommended. Most (81%) of the hospitals with written or unwritten protocols recommended the use of three-drug antiretroviral regimens, which included two nucleoside analogues and a protease inhibitor; 41% approved more than one nPEP regimen. CONCLUSIONS: A demand for nPEP is occurring in hospital EDs. The diversity of practice patterns suggests the need for evidence-based practice guidelines.

Risk factors for pneumonia and fatality in patients receiving continuous mechanical ventilation.

We studied risk factors for nosocomial pneumonia and fatality in 233 intensive care unit patients requiring continuous mechanical ventilation. Ventilator-associated pneumonia was diagnosed in 49 (21%) of the 233 patients. Of the 8 risk factors univariately associated with the development of pneumonia, only the presence of an intracranial pressure monitor (p less than 0.002), treatment with cimetidine (p less than 0.01), hospitalization during fall-winter seasons (p less than 0.04), and mechanical ventilator circuit changes every 24 h rather than every 48 h (p less than 0.02) remained significant after stepwise logistic regression. The overall fatality rate for the 49 patients who developed ventilator-associated pneumonia was 55%. Ventilator-associated pneumonia was 1 of 18 variables univariately associated with overall patient fatality, but it was not among the 7 variables present after multivariate analysis. The data delineate risk factors associated with the development of nosocomial pneumonia and fatality in patients receiving continuous mechanical ventilation.

Occupational exposure to human immunodeficiency virus (HIV) and hepatitis B virus (HBV) among embalmers: a pilot seroprevalence study.

We performed a serosurvey of 133 embalmers in an urban area where human immunodeficiency virus (HIV) infection is prevalent. Although we found histories of needlesticks to be common, and the seropositivity rate of hepatitis B virus (HBV) (13%) was approximately twice that of a blood donor comparison group, HIV antibody was uniformly absent in 129 embalmers who denied HIV risk factors, and present in one of four with self-described risk behaviors. The risk of HBV infection was higher among embalmers who have worked more than 10 years, relative risk (RR) 16.2 (95% confidence interval 2.1, 126.5), did not routinely wear gloves, RR 9.8 (CI 3.4, 28.5), or are employed in the city of Boston, RR 4.7 (CI 1.8, 12.0).

Tolerability of enteric-coated didanosine capsules compared with didanosine tablets in adults with HIV infection.

BACKGROUND: A new enteric-coated (EC) didanosine (ddI) formulation (Videx EC; Bristol-Myers Squibb, Princeton, NJ, U.S.A.) may be better tolerated than the tablet form because it lacks the buffer component thought to be responsible for diarrhea and other gastrointestinal (GI) side effects. OBJECTIVE: To evaluate the frequency and magnitude of GI side effects (nausea, bloating, GI upset, diarrhea, abdominal cramps, gas [flatus]) before and after switching the formulation of ddI, in study subjects who were experiencing one or more GI symptom(s) of at least moderate severity. METHODS: A 6-week open label crossover study of current didanosine tablet users comparing daily symptom scores (7 point scale, 0 = absent to 6 = very severe) during weeks 1 to 2 (on tablets) to weeks 4 and 6 (on EC capsules). Formulation palatability and preference, lifestyle effects, and use of antidiarrheals or other medications for symptom relief were also assessed. RESULTS: GI symptom scores (7-day means) on tablets were diarrhea 2.11, gas 2.00, bloating 1.23, abdominal cramps 0.74, GI upset 0.69, nausea 0.66. After switching to EC (week 4 and week 6), mean scores decreased for diarrhea (mean scores 0.99 week 4, 0.79 week 6), gas (0.95, 0.79), bloating (0.49, 0.32), abdominal cramps (0.21, 0.05), GI upset (0.16, 0.14), and nausea (0.32, 0.22). Severity of all GI symptoms was significantly reduced after 4 weeks on EC capsules ( p <.01 by paired t- test). Negative impact of side effects on routine activities was significantly reduced (41% on tablet vs. 7% on EC; p <.01). All 42 study subjects preferred the EC form. CONCLUSIONS: According to patients' diary scores, switching to ddI in EC form significantly reduces nausea, bloating, GI upset, diarrhea, abdominal cramps, and gas for individuals who experienced GI side effects while taking the buffered tablet form. The striking tolerability advantages appear to support routine switching to EC for such patients and may suggest that widespread preferential selection of the EC form is appropriate to enhance didanosine tolerability and promote treatment adherence.

Once-daily administration of 2',3'-dideoxyinosine (ddI) in patients with the acquired immunodeficiency syndrome or AIDS-related complex. Results of a Phase I trial.

We conducted a Phase I open-label trial of 2',3'-dideoxyinosine (ddI) for the treatment of the acquired immunodeficiency syndrome (AIDS) and severe AIDS-related complex. A single daily dose of ddI was administered orally to 34 patients (17 with AIDS and 17 with AIDS-related complex) for a median of 12 weeks (range, 2 to 56). We studied six dose levels from 1.6 to 30.4 mg per kilogram of body weight per day. Of the 17 patients previously treated with zidovudine, 13 had had hematologic side effects. The maximal tolerated dose of oral ddI was estimated to be 20.4 mg per kilogram per day. Pancreatitis and peripheral neuropathy were the major dose-limiting toxic effects. Other toxic effects included elevations in hepatic transaminase levels, abnormalities in cardiac conduction, rash, and asymptomatic elevations in serum urate levels and the creatine kinase fraction from skeletal muscle. Treatment with ddI was associated with an increase in the mean number of CD4 lymphocytes from 125 per cubic millimeter at base line to 182 per cubic millimeter after 10 weeks (P = 0.005). There were also increases after 12 weeks in the mean total lymphocyte count (from 0.8 to 1.2 x 10(9) per liter) and the mean hemoglobin level (from 12.9 to 14.1 g per deciliter) (both P less than 0.01). The amount of human immunodeficiency virus p24 antigen decreased by more than 50 percent in 14 of 19 patients with detectable antigen. No differences in response were observed between patients previously treated with zidovudine and those never treated with the drug. We conclude that ddI has antiretroviral activity in patients with AIDS or AIDS-related complex and that the toxicity of ddI differs from that of zidovudine. However, controlled trials are necessary to evaluate the efficacy of ddI.

Treatment of AIDS and AIDS-related complex with 2',3'-dideoxyinosine given once daily.

In a phase I dosage-finding trial, 2',3'-dideoxyinosine (didanosine; ddI) was administered once daily to 36 patients with AIDS or AIDS-related complex for up to 65 weeks (mean, 32.1 weeks) at six dosage levels. Thirteen of 18 patients previously treated with zidovudine had developed hematologic intolerance. The maximal tolerated dosage of ddI was 12 mg/(kg.d); dose-limiting toxicities were pancreatitis and peripheral neuropathy. Other toxicities included elevation in hepatic transaminase levels, rash, cardiac conduction abnormality, and asymptomatic hyperuricemia. Eighty-six percent of patients who completed 6 weeks of treatment showed improvement in constitutional symptoms and significant weight gain. In patients treated with ddI, the mean number of CD4+ lymphocytes increased from 124/mm3 at baseline to 199/mm3 at 24 weeks (P = .0027) and the mean leukocyte count, total lymphocyte count, and hemoglobin level showed increases (all P less than .01) after 12 weeks. Serum levels of viral p24 antigen decreased greater than or equal to 50% in 14 of 19 assessable patients. No differences between the responses of patients previously treated with zidovudine and those of zidovudine-naive patients were observed. These results indicate that ddI has significant antiretroviral activity in vivo and a toxicity profile different from that of zidovudine.

A randomized study comparing a transparent polyurethane dressing to a dry gauze dressing for peripheral intravenous catheter sites.

We studied rates of peripheral intravenous (IV) catheter tip and insertion site colonization after randomly assigning patients to transparent polyurethane (TP) dressings (N = 316) or dry gauze (DG) dressings (N = 421). The study was conducted during both summer and fall seasons, in a facility which lacked air conditioning. All patients had a teflon plastic catheter inserted, maintained and cultured by a member of the IV therapy team; no antibiotic or antiseptic ointments were used. Colonization rates were higher in the summer than in the fall for both catheter tips (9.0% vs 3.5%, p = 0.005) and sites (21.6% vs 7.0%, p = 0.001). During the summer season, the rate of catheter tip colonization with TP dressings was nearly twice that of DG dressings (12.4% vs 6.8%, p = 0.04). Logistic regression analysis indicated that catheter tip colonization was associated with the summer season (odds ratio = 3.0, 95% CI 1.4-6.2) and TP dressings (odds ratio = 1.8, 95% CI 1.1-3.2), and that site colonization was associated with both summer (odds ratio = 4.0, 95% CI 2.2-7.1) and receipt of antibiotics (odds ratio = 1.9, 95% CI 1.1-3.2). Coagulase-negative staphylococci were isolated from 55.5% of the colonized catheter tips and insertion sites. The data suggest that bacterial colonization of peripheral IV catheters is increased in summer, and that use of TP dressings may increase both tip colonization and cost nearly twofold.

Nonresponsiveness to hepatitis B vaccine in health care workers. Results of revaccination and genetic typings.

Twenty-eight health care workers who had a poor antibody response when initially vaccinated with hepatitis B vaccine were revaccinated with three additional 20-microgram doses. Eight of the twenty nonresponders, who had levels of antibody to hepatitis B surface antigen (anti-HBs) of less than 8 estimated radioimmunoassay (RIA) units, and all 8 of the hyporesponders, who had anti-HBs levels of 8 or 16 RIA units, attained anti-HBs levels of 36 RIA units or more after revaccination. Tests for HLA-A, B, C, and DR; for complement proteins C2, C4A, C4B, and BF; and for the erythrocyte enzyme glyoxalase I were done in 17 nonresponders and 3 hyporesponders. Nine (45%) had HLA-DR7 and 8 (40%) had HLA-DR3, compared with an expected rate of 23% in the general population. At least one of two extended haplotypes (B44, DR7, FC31 or B8, DR3, SCO1) were detected in 6 of the 9 who did not respond to revaccination, compared with 2 of 11 who responded to a second course of vaccine. Poor responders to vaccine may benefit from revaccination, and genetic factors may modulate the immune response to vaccination.

Nosocomial pneumonia in intubated patients given sucralfate as compared with antacids or histamine type 2 blockers. The role of gastric colonization.

Gram-negative nosocomial pneumonia may result from retrograde colonization of the pharynx from the stomach, and this may be more likely when the gastric pH is relatively high. We studied the rate of nosocomial pneumonia among 130 patients given mechanical ventilation in an intensive care unit who were receiving as prophylaxis for stress ulcer either sucralfate (n = 61), which does not raise gastric pH, or conventional treatment with antacids, histamine type 2 (H2) blockers, or both (n = 69). At the time of randomization to treatment, the two groups were similar in age, underlying diseases, and severity of acute illness. Patients in the sucralfate group had a higher proportion of gastric aspirates with a pH less than or equal to 4 (P less than 0.001) and significantly lower concentrations of gram-negative bacilli (P less than 0.05) in gastric aspirates, pharyngeal swabs, and tracheal aspirates than did patients in the antacid-H2-blocker group. The rate of pneumonia was twice as high in the antacid-H2 group as in the sucralfate group (95 percent confidence interval, 0.89 to 4.58; P = 0.11). Gram-negative bacilli were isolated more frequently from the tracheal aspirates of patients with pneumonia who were receiving antacids or H2 blockers. Mortality rates were 1.6 times higher in the antacid-H2 group than in the sucralfate group (95 percent confidence interval, 0.99 to 2.50; P = 0.07). Although our results fell just short of statistical significance when they were analyzed according to intention to treat, they suggest that agents that elevate gastric pH increase the risk of nosocomial pneumonia in patients receiving ventilation by favoring gastric colonization with gram-negative bacilli. We conclude that in patients receiving mechanical ventilation, the use of a prophylactic agent against stress-ulcer bleeding that preserves the natural gastric acid barrier against bacterial overgrowth may be preferable to antacids and H2 blockers.