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RATIONALE: Severe community-acquired pneumonia (sCAP) is a leading cause of death worldwide. Adjunctive therapies for sCAP are needed to further improve outcome. A systemic inhibitor of coagulation, tifacogin (recombinant human tissue factor pathway inhibitor) seemed to provide mortality benefit in the sCAP subgroup of a previous sepsis trial. OBJECTIVES: Evaluate the impact of adjunctive tifacogin on mortality in patients with sCAP. METHODS: A multicenter, randomized, placebo-controlled, double-blind, three-arm study was conducted from July 2005 to June 2008 at 188 centers in North and South America, Europe, South Africa, Asia, Australia, and New Zealand. Adults with sCAP were randomized to receive a continuous intravenous infusion of tifacogin 0.025 mg/kg/h, tifacogin 0.075 mg/kg/h, or matching placebo over 96 hours. MEASUREMENTS AND MAIN RESULTS: Severity-adjusted 28-day all-cause mortality. Of 2,138 randomized patients, 946, 238, and 918 received tifacogin 0.025 mg/kg/h, tifacogin 0.075 mg/kg/h, and placebo, respectively. Tifacogin 0.075 mg/kg/h was discontinued after the first interim analysis according to prespecified futility criterion. The 28-day all-cause mortality rates were similar between the 0.025 mg/kg/h (18%) and placebo groups (17.9%) (P = 0.56). Greater reduction in prothrombin fragment 1+2 and thrombin antithrombin complexes levels relative to baseline throughout the first 96 hours was found with tifacogin 0.025 mg/kg/h than with placebo. The incidence of adverse events and serious adverse events were comparable between the tifacogin 0.025 mg/kg/h and placebo groups. CONCLUSIONS: Tifacogin showed no mortality benefit in patients with sCAP despite evidence of biologic activity. [ABSTRACT FROM AUTHOR]

Background: The treatment of giant cell arteritis with glucocorticoid-sparing agents is an unmet medical need. We evaluated the efficacy and safety of secukinumab, an anti-interleukin-17A monoclonal antibody, in patients with giant cell arteritis., Methods: We conducted a Bayesian randomised, parallel-group, double-blind, placebo-controlled, multicentre, phase 2 study at 11 clinics or hospitals in Germany. Patients aged 50 years or older with new-onset or relapsing giant cell arteritis who were naive to biological therapy and already receiving glucocorticoids with a prednisolone equivalent dose of 25-60 mg/day were eligible for inclusion. Participants were assigned (1:1) to receive 300 mg secukinumab or placebo subcutaneously once a week up to week 4 and every 4 weeks thereafter. In both treatment groups, prednisolone dose was tapered down to 0 mg over a 26-week period. Patients, investigator staff, and clinical trial team were masked to the treatment assignment. The primary endpoint was the median proportion (Bayesian analysis) of patients with sustained remission until week 28 in the full analysis set (ie, all patients who received at least one dose of assigned treatment, analysed according to treatment assigned at randomisation). Sustained remission rate of the placebo group from a previous trial of tocilizumab in patients with giant cell arteritis was used to derive the prior distribution of placebo sustained remission rate for the primary endpoint. The safety of secukinumab was assessed in the safety set (ie, all patients who received at least one dose of study treatment, analysed according to study treatment received). This trial is completed and is registered with ClinicalTrials.gov, NCT03765788., Findings: Of the 65 patients who were assessed for eligibility, 52 patients (median age 75 years [IQR 69-79]; 35 [67%] female and 17 [33%] male, 52 [100%] White) were enrolled between Jan 30, 2019 and March 30, 2020 and were randomly assigned to receive secukinumab (n=27) or placebo (n=25). Four of 27 patients in the secukinumab group and eight of 25 patients in the placebo group discontinued treatment by week 28 of the study. On the basis of the Bayesian analysis, the median proportion of patients in sustained remission until week 28 was 70% (95% credibility interval 52-85) in the secukinumab group versus 20% (12-30) in the placebo group. The incidence of adverse events was similar in the secukinumab (27 [100%] of 27 patients had any adverse event) and placebo groups (24 [96%] of 25 patients had any adverse event); the most common adverse events were hypertension (six [22%] of 27 patients in the secukinumab group and eight [32%] of 25 patients in the placebo group) and nasopharyngitis (five [19%] of 27 patients in the secukinumab group and five [20%] of 25 patients in the placebo group). Two patients (one in each group) died during the study, neither of which was considered to be related to study treatment., Interpretation: Patients with active giant cell arteritis had a higher sustained remission rate in the secukinumab group than in the placebo group at week 28, in combination with glucocorticoid taper regimen. Secukinumab was tolerated well with no new safety concerns. This proof-of-concept phase 2 study further supports the development of secukinumab as a treatment option for people with giant cell arteritis., Funding: Novartis Pharma., Competing Interests: Declaration of interests NV declares speaker honorarium from AbbVie, AstraZeneca, Novartis, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Roche, UCB, GlaxoSmithKline, and Vifor; being an advisory board member for AbbVie, Chugai, Novartis, UCB, and Vifor; consulting fees from Novartis, AbbVie, Chugai, and Vifor; research grants from Bristol Myers Squibb and Novartis; meeting or travel grants from Bristol Myers Squibb, Novartis, AbbVie, and Vifor; and expert testimony for Novartis, Vifor, and AbbVie. WAS is part of speaker bureaus for AbbVie, Chugai, Medac, Novartis, Roche, and Sanofi; is an advisory board member for AbbVie, Chugai, GlaxoSmithKline, Novartis, Roche, and Sanofi; and received research grants from AbbVie, GlaxoSmithKline, Novartis, and Sanofi. RB is part of speaker bureaus for AbbVie, Bristol Myers Squibb, Chugai, Novartis, Roche, Galapagos, and Glaxo Smith Kline; is an advisory board member for Galapagos, GlaxoSmithKline, and Vifor; received research grants from Vifor; and is an unpaid board member for Commission für student education—German Rheumatology Society. JR is part of speaker bureaus for AbbVie, Biogen, Bristol Myers Squibb, Chugai, GlaxoSmithKline, Janssen, Lilly, MSD, Novartis, Roche, Sanofi, Sobi, and UCB and received consulting fees from AbbVie, Biogen, Bristol Myers Squibb, Chugai, GlaxoSmithKline, Janssen, Lilly, MSD, Novartis, Roche, Sanofi, Sobi, and UCB. LU received payments for speeches and seminar presentations from Novartis. H-PT is an advisory board member for AbbVie, Bristol Myers Squibb, Chugai, Gilead, Lilly, Novartis, Roche, and Sanofi. SF received consulting fees from Amgen and Novartis; speaker honorarium from AbbVie, Amgen, Galapagos, Novartis, and UCB; and meeting or travel grants from Novartis, UCB, Galapagos, and Sobi. IA received consulting fees from Amgen, Boehringer Ingelheim, Chugai, Galapagos, Lilly, Novartis, Pfizer, Sobi, Takeda, and UCB; is part of speaker bureaus for AbbVie, Chugai, Gilead, Lilly, MSD, Novartis, Pfizer, Sobi, and UCB; received payments for other services (receipt of equipment, materials, drugs, medical writing, and gifts) from Novartis; and received research grants from Lilly. SMW is an advisory board member for Novartis; received speaker honorarium from AbbVie, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Daiichi-Sankyo, MSD, Novartis, Otsuka, Pfizer, and Roche; received meeting or travel grants from Abbvie, Amgen, Bristol Myers Squibb, Otsuka, Pfizer, and UCB; and is an unpaid board member for Saarländisch-Pfälzische Internistengesellschaft and Arbeitskreis Nephrologie Saar-Pfalz Mosel. PL received speaker honorarium from Bristol Myers Squibb, GlaxoSmithKline, Janssen, UCB, and Vifor; is an advisory board member for GlaxoSmithKline and Vifor; and received research grants from Bundesministerium für Bildung und Forschung, Deutsche Forschungsgemeinschaft, John Grube Foundation, and Vifor. HS-K is part of speaker bureaus for AbbVie, Bristol Myers Squibb, Chugai, GlaxoSmithKline, Janssen, Medac, Novartis, Pfizer, Roche, Sanofi, and UCB; is an advisory board member for AbbVie, Bristol Myers Squibb, Chugai, Janssen, Medac, Pfizer, Novartis, Roche, Sanofi, and UCB; and received research grants from AbbVie and Novartis. CA is an employee of Novartis Pharma. EP is an employee of Novartis Pharma and owns Novartis stock. MHM is an employee and shareholder of Novartis Pharmaceuticals and is named on the patent for secukinumab in the treatment of giant cell arteritis, as an employee of Novartis, the funder. CS is an employee of Novartis Pharma and has Novartis stock options. MM is an employee of Novartis Pharma. JT declares speaker honorarium from Novartis, GlaxoSmithKline, Bristol Myers Squibb, Roche, AstraZeneca, and Vifor; is an advisory board member for Novartis; received consulting fees from Novartis, Janssen, and GlaxoSmithKline; and received research grants from Bristol Myers Squibb and Novartis. DMK declares no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: Data are lacking on the burden of chronic idiopathic urticaria (CIU) versus other dermatologic conditions. This analysis compared the burden of chronic urticaria (CU, proxy for CIU) with psoriasis., Methods: Data from CU (N = 747) and psoriasis patients (N = 5107) came from 2010 to 2012 US National Health and Wellness Surveys. Outcomes included SF-12v2/SF-36v2 mental and physical component summary scores (MCS and PCS, respectively) and other health/activity-related measures., Results: MCS score was 44.7 for CU, and 48.2, 44.7 and 44.3 for mild/moderate/severe psoriasis, respectively (US norm = 50). PCS score was 43.8 for CU, and 46.5, 44.1 and 40.3 for mild/moderate/severe psoriasis. Health utility score was 0.67 for CU, and 0.72, 0.67 and 0.65 for mild/moderate/severe psoriasis. More CU patients reported depression (39%), anxiety (42%) and sleep difficulties (50%) than psoriasis patients (any severity). Overall work impairment was 29% for CU, and 19%, 26% and 31% for mild/moderate/severe psoriasis. Activities impairment was 39% for CU, and 28%, 37% and 43% for mild/moderate/severe psoriasis. CU and psoriasis patients had frequent healthcare visits., Conclusions: Patients with CU had impaired mental/physical health and work/non-work activities, similar to moderate-to-severe psoriasis patients. Results suggest that better disease management of CU is needed. This analysis should also reflect the significant burden of CIU.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of ventilator-associated pneumonia (VAP). This prospective, open-label, multicenter clinical trial compared the early microbiological efficacy of linezolid (LZD) therapy with that of vancomycin (VAN) therapy in patients with MRSA VAP., Methods: A total of 149 patients with suspected MRSA VAP were randomized to receive either LZD, 600 mg, or VAN, 1 g every 12 h. Patients with baseline bronchoscopic BAL (BBAL) fluid quantitative culture findings that were positive for MRSA (>or= 10(4) cfu/mL) comprised the study population. The primary outcome was microbiological response (

Objective: To assess the prevalence of HIV antiretroviral resistance among source patients for occupational HIV exposures., Design: Blood and data (eg, stage of HIV, previous antiretroviral drug therapy, and HIV RNA viral load) were collected from HIV-infected patients who were source patients for occupational exposures., Setting: Seven tertiary-care medical centers in five U.S. cities (San Diego, California; Miami, Florida; Boston, Massachusetts; Albany, New York; and New York, New York [three sites]) during 1998 to 1999., Participants: Sixty-four HIV-infected patients who were source patients for occupational exposures., Results: Virus from 50 patients was sequenced; virus from 14 patients with an undetectable (ie, < 400 RNA copies/mL) viral load could not be sequenced. Overall, 19 (38%) of the 50 patients had primary genotypic mutations associated with resistance to reverse transcriptase or protease inhibitors. Eighteen of the 19 viruses with primary mutations and 13 wild type viruses were phenotyped by recombinant assays; 19 had phenotypic resistance to at least one antiretroviral agent. Of the 50 source patients studied, 26 had taken antiretroviral agents in the 3 months before the occupational exposure incident. Sixteen (62%) of the 26 drug-treated patients had virus that was phenotypically resistant to at least one drug. Four (17%) of 23 untreated patients had phenotypically resistant virus. No episodes of HIV transmission were observed among the exposed HCWs., Conclusions: There was a high prevalence of drug-resistant HIV among source patients for occupational HIV exposures. Healthcare providers should use the drug treatment information of source patients when making decisions about post-exposure prophylaxis.

Background: The purpose of this study was to determine the prevalence of adenoviral infection in pediatric small bowel transplantation (SBT) recipients, examine risk factors for progression to histologic disease, and examine the impact of adenovirus on outcome., Methods: Beginning in July 2000, all SBT recipients had viral cultures for adenovirus, cytomegalovirus (CMV), and herpes simplex virus (HSV) obtained routinely during graft biopsies. The medical records were retrospectively reviewed for frequency and site of viral culture, types and doses of immunosuppressive drugs, episodes of rejection, histology of allograft biopsies, and other infections. Adenoviral isolates were typed by polymerase chain reaction and type-specific neutralization assays., Results: All 14 SBT recipients who met enrollment criteria had evidence of adenoviral infection (intestinal graft, 13; liver graft, 1). Eight of 14 developed histologic disease with identifiable adenoviral intranuclear inclusions. In contrast, CMV enteritis was identified in only one patient, who subsequently also developed adenoviral disease. No other viruses were detected. Adenoviral cultures were first positive within 30 days of transplant in nine. Patients with histologic disease were more likely than those without to have received intensive corticosteroid therapy (P<0.007), had virus isolated from more than one site (P=0.03), and had persistent positive cultures (P<0.01)., Conclusions: Adenovirus was commonly isolated from children undergoing intestinal transplantation. Progression to disease may be associated with more intensive immunosuppressive therapy and inability to clear virus.

Objective: To compare the percutaneous injury rate associated with a standard versus a safety resheathable winged steel (butterfly) needle., Design: Before-after trial of winged steel needle injuries during a 33-month period (19-month baseline, 3-month training, and 11-month study intervention), followed by a 31-month poststudy period., Setting: A 1,190-bed acute care referral hospital with inpatient and outpatient services in New York City., Participants: All healthcare workers performing intravascular-access procedures with winged steel needles., Intervention: Safety resheathable winged steel needle., Results: The injury rate associated with winged steel needles declined from 13.41 to 6.41 per 100,000 (relative risk [RR], 0.48; 95% confidence interval [CI95], 0.31 to 0.73) following implementation of the safety device. Injuries occurring during or after disposal were reduced most substantially (RR, 0.15; CI95, 0.06 to 0.43). Safety winged steel needle injuries occurred most often before activation of the safety mechanism was appropriate (39%); 32% were due to the user choosing not to activate the device, 21% occurred during activation, and 4% were due to improper activation. Preference for the safety winged steel needle over the standard device was 63%. The safety feature was activated in 83% of the samples examined during audits of disposal containers. Following completion of the study, the safety winged steel needle injury rate (7.29 per 100,000) did not differ significantly from the winged steel needle injury rate during the study period., Conclusion: Implementation of a safety resheathable winged steel needle substantially reduced injuries among healthcare workers performing vascular-access procedures. The residual risk of injury associated with this device can be reduced further with increased compliance with proper activation procedures.

To estimate the incidence of and assess risk factors for occupational Mycobacterium tuberculosis transmission to health care personnel (HCP) in 5 New York City and Boston health care facilities, performance of prospective tuberculin skin tests (TSTs) was conducted from April 1994 through October 1995. Two-step testing was used at the enrollment of 2198 HCP with negative TST results. Follow-up visits were scheduled for every 6 months. Thirty (1.5%) of 1960 HCP with >/=1 follow-up evaluation had TST conversion (that is, an increase in TST induration of >/=10 mm). Independent risk factors for TST conversion were entering the United States after 1991 and inclusion in a tuberculosis-contact investigation in the workplace. These findings suggest that occupational transmission of M. tuberculosis occurred, as well as possible nonoccupational transmission or late boosting among foreign-born HCP who recently entered the United States. These results demonstrate the difficulty in interpreting TST results and estimating conversion rates among HCP, especially when large proportions of foreign-born HCP are included in surveillance.

We report a case of myositis that resulted from disseminated cryptococcosis in a patient with hepatitis C cirrhosis. One year after cessation of treatment, the patient remains symptom free with negative results of serum cryptococcal antigen tests and negative culture results.

Objective: To assess the effect on staff- and patient-related complications of a needleless intermittent intravenous access system with a reflux valve for peripheral infusions., Design: A 6-month cross-over clinical trial (phase I, 13 weeks; phase II, 12 weeks) of a needleless intermittent intravenous access system (NL; study device) compared to a conventional heparin-lock system (CHL, control device) was performed during 1991 on 16 medical and surgical units. A random selection of patients was assessed for local intravenous-site complications; all patients were assessed for the development of nosocomial bacteremia and device-related complications. Staff were assessed for percutaneous injuries and participated in completion of product evaluations. A cost analysis of the study compared to the control device was performed., Setting: A 1,100-bed, teaching, referral medical center. PATIENTS AND STAFF PARTICIPANTS: 594 patients during 602 patient admissions, comprising a random sample of all patients with a study or control device inserted within a previous 24-hour period on study and control units, were assessed for local complications. The 16 units included adult inpatient general medicine, surgical, and subspecialty units. Pediatrics, obstetrics-gynecology, and intensive-care units were excluded. All patients on study and control units were assessed for development of nosocomial bacteremia and device-related complications. All staff who utilized, manipulated, or may have been exposed to sharps on study and control units were assessed for percutaneous injuries. Nursing staff completed product evaluations., Intervention: The study device, a needleless intermittent intravenous access system with a reflux valve, was compared to the control device, a conventional heparin lock, for peripheral infusions., Results: During the study, 35 percutaneous injuries were reported. Eight injuries were CHL-related; no NL-related injuries were reported (P=.007). An evaluation of 602 patient admissions, 1,134 intermittent access devices, and 2,268 observed indwelling device days demonstrated more pain at the insertion site for CHL than NL; however, no differences in objective signs of phlebitis were noted. Of 773 episodes of positive blood cultures on study and control units, 6 (0.8%) were device-related (assessed by blinded investigator), with no difference between NL and CHL. Complications, including difficulty with infusion (P<.001) and disconnection of intravenous tubing from device (P<.001), were reported more frequently with CHL than with NL. Of nursing staff responding to a product evaluation survey, 95.2% preferred the study over control device. The projected annual incremental cost to our institution for hospitalwide implementation of NL for intermittent access for peripheral infusions was estimated at $82,845, or $230 per 1,000 patient days., Conclusions: A needleless intermittent intravenous access system with a reflux valve for peripheral infusions is effective in reducing percutaneous injuries to staff and is not associated with an increase in either insertion-site complications or nosocomial bacteremia. Institutions should consider these data, available institutional resources, and institution-specific data regarding the frequency and risk of intermittent access-device-related injuries and other types of sharps injuries in their staff when selecting the above or other safety devices.

A case of spontaneous pneumomediastinum secondary to hyperemesis gravidarum is presented. The pathophysiology, clinical presentation, differential diagnosis, and management of this unusual complication of hyperemesis gravidarum are reviewed.

We report the frequency and type of infectious ocular complications following orthotopic liver transplantation (OLT) and review diagnostic and therapeutic strategies. During the period September 1988 through November 1994, 684 patients underwent OLT at Mount Sinai Hospital (New York). Nine orthotopic liver transplant patients (1.3%) developed ocular infections: Candida albicans endophthalmitis (2), Aspergillus fumigatus endophthalmitis (1), cytomegalovirus retinitis (4), herpes simplex virus keratitis (1), and varicella-zoster virus panophthalmitis (1). The mean time from OLT to ocular symptoms was 42 days for patients with fungal infections and 128 days for patients with viral infections. Blurred vision was the commonest symptom (five of nine cases). The mean duration of follow-up was 2 years (range, 33 days to 5 years). Permanent loss of vision occurred in three patients, five had improvement in visual acuity, and one died of disseminated aspergillosis 33 days after OLT. Infectious ocular complications following OLT may occur as isolated events or with disseminated disease. Fungal infections occur earlier (mean, 42 days after OLT) than viral infections (mean, 4 months after OLT). The clinical presentation may be atypical; aggressive vitreoretinal procedures and serial examinations may be required to establish the diagnosis. Cytomegalovirus retinitis in orthotopic liver transplant patients may not require life-long maintenance therapy with antiviral agents.

The risk factors for acquisition of and mortality due to nosocomial infection with vancomycin-resistant Enterococcus faecium (VREF) in orthotopic liver transplant (OLT) recipients were studied at a tertiary care hospital; 32 VREF-infected OLT patients (cases) were compared with 33 randomly selected OLT recipients (controls). More antibiotics were administered preoperatively to cases (mean, 4 antibiotics per patient for 474 antibiotic-days) than to controls (mean, 1.8 antibiotics per patient for 131 antibiotic-days). Cases were more likely than controls to have received vancomycin therapy preoperatively and to have been hospitalized in the intensive care unit (ICU) preoperatively. Logistic regression revealed that the risk factors for acquisition of VREF infection were surgical reexploration and a prolonged stay in the surgical ICU postoperatively. In the cases, the risk factors for mortality were admission to the ICU preoperatively and hemodialysis. The mortality rate associated with polymicrobial bloodstream infections was 100% despite appropriate therapy. Sixteen and 18 cases received parenteral chloramphenicol and doxycycline, respectively, for treatment of VREF infection. There were no hematologic adverse effects attributed to chloramphenicol treatment. DNA analysis of selected E. faecium isolates suggested that infections were due to multiple clones. In summary, the source of VREF infection in OLT patients is the gastrointestinal tract. Antibiotic selective pressure may contribute to colonization. Infection with VREF is a predictor of morbidity and mortality in OLT patients.

Objective: To study the epidemiology and preventability of blood contact with skin and mucous membranes during surgical procedures., Design: Observers present at 1,382 surgical procedures recorded information about the procedure, the personnel present, and the contacts that occurred., Setting: Four US teaching hospitals during 1990., Participants: Operating room personnel in five surgical specialties., Main Outcome Measures: Numbers and circumstances of contact between the patient's blood (or other infective fluids) and surgical personnel's mucous membranes (mucous membrane contacts) or skin (skin contacts, excluding percutaneous injuries)., Results: A total of 1,069 skin (including 620 hand, 258 body, and 172 face) and 32 mucous membrane (all affecting eyes) contacts were observed. Surgeons sustained most contacts (19% had > or = 1 skin contact and 0.5% had > or = 1 mucous membrane-eye contact). Hand contacts were 72% lower among surgeons who double gloved, and face contacts were prevented reliably by face shields. Mucous membrane-eye contacts were significantly less frequent in surgeons wearing eyeglasses and were absent in surgeons wearing goggles or face shields. Among surgeons, risk factors for skin contact depended on the area of contact: hand contacts were associated most closely with procedure duration (adjusted odds ratio [OR], 9.4; > or = 4 versus < 1 hour); body contacts (arms, legs, and torso) with estimated blood losses (adjusted OR, 8.4; > or = 1,000 versus < 100 mL); and face contacts, with orthopedic service (adjusted OR, 7.5 compared with general surgery)., Conclusion: Skin and mucous membrane contacts are preventable by appropriate barrier precautions, yet occur commonly during surgery. Surgeons who perform procedures similar to those included in this study should strongly consider double gloving, changing gloves routinely during surgery, or both.

Study Objective: To assess the nature and frequency of blood contact (BC) among emergency medical service (EMS) workers., Design: During an 8-month period, we interviewed EMS workers returning from emergency transport calls on a sample of shifts. We simultaneously conducted an HIV seroprevalence survey among EMS-transported patients at receiving hospitals served by these workers., Setting: Three US cities with high AIDS incidence., Participants: EMS workers., Results: During 165 shifts, 2,472 patients were attended. Sixty-two BCs (1 needlestick and 61 skin contacts) were reported. Individual EMS workers had a mean of 1.25 BCs, including .02 percutaneous exposures, per 100 patients attended. The estimated annual frequency of BC for an EMS worker at the study sites was 12.3, including .2 percutaneous exposures. For 93.5% of the BCs, the HIV serostatus of the source patients was unknown to the EMS worker. HIV seroprevalences among EMS-transported patients at the three receiving hospital emergency departments were 8.3, 7.7, and 4.1 per 100 patients; the highest rates were among male patients 15 to 44 years old who presented with pneumonia., Conclusion: EMS personnel regularly experience BCs, most of which are skin contacts. Because the HIV serostatus of the patient is usually unknown, EMS workers should practice universal precautions. Postexposure management should include a mechanism for voluntary HIV counseling and testing of the patient after transport and transmittal of the results to the EMS.

The authors conducted an observational study of the frequency and circumstances of percutaneous injuries among dental residents. Their findings suggest that most percutaneous injuries sustained by these dental residents occurred extraorally and were associated with denture impression procedures. Some injuries may be preventable with changes in techniques or instrument design.

Objective: To characterize disposal-related sharps injuries., Design: A three-part study including (a) descriptive analysis of disposal-related injuries in a 1-year period, (b) 4:1 matched case-control study of nurses injured while using sharps disposal containers, and (c) survey to solicit opinions of users of containers., Setting: An 1,181-bed teaching hospital in New York City., Participants: For epidemiologic analyses, persons with self-reported injuries identified via New York State and Occupational Safety and Health Administration forms and control nurses without self-reported injuries. For survey, convenience sample of hospital nurses, laboratory workers, and maintenance workers., Main Outcome Measures: Circumstances of injuries determined by study questionnaires. Employee opinions obtained by questionnaires and discussions during small group sessions., Results: Three hundred sixty-one persons reported sharps injuries, of whom 72 (20%) had disposal-related injuries. Persons with disposal-related injuries included four hospital visitors and one patient. Of 67 disposal-related injuries among employees, 25 (37%) directly involved use of a sharps disposal container. Significant risk factors for injury included container height greater than 4 ft above the floor, distance less than 5 ft from site of sharp object use to nearest container, and lack of attendance at universal precautions inservice classes. Survey groups involved 69 employees who identified a variety of preferred features for sharps disposal containers., Conclusions: Disposal of sharp objects is an important cause of sharps injuries. Ergonomic factors, worker education, and appropriate container design should be considered in injury prevention strategies. Relevant guidelines and regulations are lacking and are needed.

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.

Tuberculosis has been increasing especially in urban areas and in immunosuppressed patients; however, the incidence and factors associated with tuberculosis in OLT patients are unknown. Five of 550 patients who underwent OLT at the Mount Sinai Medical Center during a 5-year period were noted to have tuberculosis. The mean age of the patients was 49.2 years; there were 3 males and 2 females and 3 were foreign born. One of 5 had a prior history of tuberculosis. Tuberculin skin tests performed before transplant revealed 1 positive and 2 anergic reactions. The preoperative chest x-ray revealed apical fibrosis in 2 patients and bilateral apical disease with a nodule in 1 patient. Tuberculosis developed from 2 to 57 months after surgery in 4/5 patients. One had miliary lesions of the peritoneum discovered at the time of OLT. One patient had recent contact with a patient with pulmonary tuberculosis. At presentation, fever was present in 4 of 5 patients, pulmonary lesions in 3 patients, meningitis in 2; during hospitalization, 1 had a liver abscess and disseminated intravascular coagulation and peripheral gangrene. Lymphocytosis was noted in the pleural (1), peritoneal (1), and cerebrospinal fluid (1). Acid-fast smears were positive in bronchoalveolar lavage fluid (1), peritoneal isolates (1), and liver biopsy (1). All patients had positive cultures for Mycobacterium tuberculosis. These isolates were all sensitive to isoniazid, streptomycin, rifampin, ethambutol, and pyrazinamide. Four of 5 patients were treated with isoniazid and rifampin, 2 received pyrazinamide, 2, amikacin, 2, ofloxacin, and 2, ethambutol. Three of 5 patients are doing well on antituberculous therapy and 2 expired with tuberculosis as the cause of death. In OLT patients with unexplained fever, tuberculosis including extrapulmonary and disseminated disease should be considered since the mortality rate is very high. Liver transplantation can be performed in the presence of active peritoneal tuberculosis with the use of judicious antituberculous therapy. The role of preventive therapy is controversial, though use in certain high risk patients is suggested.

Twenty-seven episodes of Pseudomonas aeruginosa bacteremia in 21 patients with AIDS were evaluated at the Mount Sinai Medical Center in 1987-1992. Of 21 primary episodes, 12 were acquired in the community, 8 were nosocomial, and one was acquired in a nursing home. Sources of bacteremia (i.e., sites of infection; n = 30) included the lungs (12 cases) an indwelling vascular catheter (9), and the upper respiratory tract (5, including 2 cases of sinusitis, 2 cases of malignant external otitis, and 1 case of epiglottis/pharyngeal cellulitis); in 4 cases the source was unknown. White blood cell counts ranged from 0.1 to 26.2 (mean, 4.32) x 10(3)/mm3; in 19 of 26 cases, the absolute neutrophil count was > 1 x 10(3)/mm3. With the exclusion of primary episodes of bacteremia that resulted in death, the rate of relapse was 33.3% (5 of 15 cases). Mortality for the 25 evaluable episodes of bacteremia was 40% (32% for primary infection and 80% for relapse; P = .06); 52.6% of evaluable patients (10 of 19) ultimately died of P. aeruginosa bacteremia. The institution of appropriate therapy at presentation did not positively affect outcome. Rates of response were higher among episodes treated with a drug combination (an antipseudomonal beta-lactam or monobactam antibiotic plus an aminoglycoside) than among those treated with a single agent (P = .036).

Aztreonam is a monobactam exhibiting an antibacterial spectrum similar to that of the aminoglycosides, with activity against aerobic gram-negative bacilli, and is the only related drug that may be given to patients hypersensitive to beta-lactams. The pharmacokinetics of aztreonam were compared in two groups of healthy volunteers. The young group comprised 10 adults between the ages of 18 and 30 years, and the elderly group included 10 adults older than 65 years of age. The two groups each received two doses (1 and 2 g) aztreonam, separated by 1 week. Although the mean peak serum concentrations of aztreonam for the two groups were similar, there were differences in other pharmacokinetic parameters. For example, for the 2-g dose the mean half-life (1.8 +/- .51 versus 3.1 +/- .9 hour), and area under the curve (AUC) (294.42 +/- 64.08 versus 469.01 +/- 144.02 micrograms x hour/mL per 1.73 m2) were less for the younger group compared with the elderly group. The mean total body clearance of aztreonam was greater for the younger than the elderly group. The results were similar to the pharmacokinetic parameters derived from the 1-g dose. These results mirror the lower creatinine clearances and higher serum creatinine levels found in the elderly group. The data suggest that lower doses of aztreonam given at less frequent intervals may be appropriate in the elderly population.

Purpose: To estimate (1) the prevalence of human immunodeficiency virus (HIV) infection in emergency department (ED) patients, (2) the frequency of blood contact (BC) in ED workers (EDWs), (3) the efficacy of gloves in preventing BC, and (4) the risk of HIV infection in EDWs due to BC., Patients and Methods: We conducted an 8-month study in three pairs of inner-city and suburban hospital EDs in high AIDS incidence areas in the United States. At each hospital, blood specimens from approximately 3,400 ED patients were tested for HIV antibody. Observers monitored BC and glove use by EDWs., Results: HIV seroprevalence was 4.1 to 8.9 per 100 patient visits in the 3 inner-city EDs, 6.1 in 1 suburban ED, and 0.2 and 0.7 in the other 2 suburban EDs. The HIV infection status of 69% of the infected patients was unknown to ED staff. Seroprevalence rates were highest among patients aged 15 to 44 years, males, blacks and Hispanics, and patients with pneumonia. BC was observed in 379 (3.9%) of 9,793 procedures; 362 (95%) of the BCs were on skin, 11 (3%) were on mucous membranes, and 6 (2%) were percutaneous. Overall procedure-adjusted skin BC rates were 11.2 BCs per 100 procedures for ungloved workers and 1.3 for gloved EDWs (relative risk = 8.8; 95% confidence interval = 7.3 to 10.3). In the high HIV seroprevalence EDs studied, 1 in every 40 full-time ED physicians or nurses can expect an HIV-positive percutaneous BC annually; in the low HIV seroprevalence EDs studied, 1 in every 575. The annual occupational risk of HIV infection for an individual ED physician or nurse from performing procedures observed in this study is estimated as 0.008% to 0.026% (1 in 13,100 to 1 in 3,800) in a high HIV seroprevalence area and 0.0005% to 0.002% (1 in 187,000 to 1 in 55,000) in a low HIV seroprevalence area., Conclusions: In both inner-city and suburban EDs, patient HIV seroprevalence varies with patient demographics and clinical presentation; the infection status of most HIV-positive patients is unknown to ED staff. The risk to an EDW of occupationally acquiring HIV infection varies by ED location and the nature and frequency of BC; this risk can be reduced by adherence to universal precautions.

Objective: To study the numbers and circumstances of percutaneous injuries (eg, needle sticks, cuts) that occur during surgical procedures. Surgical personnel risk infection with blood-borne pathogens from percutaneous injuries; some injuries might also place patients at risk by exposing them to a health care worker's blood., Design: Observers present at 1382 surgical procedures recorded information about the procedure, the personnel present, and percutaneous injuries that occurred., Setting: Four US teaching hospitals during 1990., Participants: Operating room personnel in five surgical specialties., Main Outcome Measures: Numbers and circumstances of percutaneous injuries among surgical personnel and instances in which surgical instruments that had injured a worker recontacted the patient's surgical wound., Results: Ninety-nine injuries occurred during 95 (6.9%) of the 1382 procedures. Seventy-six injuries (77%) were caused by suture needles and affected the nondominant hand (62 injuries [63%]), especially the distal forefinger. The risk of injury adjusted for confounding variables by logistic regression was higher during vaginal hysterectomy (odds ratio [OR], 3.5; 95% confidence interval [CI], 1.6 to 7.5) and lower during certain orthopedic procedures (OR, 0.2; CI, 0.1 to 0.7) than during 11 other types of procedures (reference group; OR, 1.0). Use of fingers rather than an instrument to hold the tissue being sutured was associated with 35 injuries (35%). Eighty-eight injuries (89%) were sustained by resident or attending surgeons; in 28 (32%) of the 88 injuries in surgeons, the sharp object that caused the injury recontacted the patient., Conclusion: Percutaneous injuries occur regularly during surgery, placing surgical personnel and, to a lesser extent, patients at risk for infection with blood-borne pathogens. Many such injuries may be preventable with changes in devices, techniques, or protective equipment; all such measures require careful evaluation to determine their efficacy in reducing injury and their effect on patient care.

The pharmacokinetics of ampicillin-sulbactam in elderly subjects (65 to 85 years; group 3, n = 8), compared with those in middle-aged (41 to 64 years; group 2, n = 8) and younger (20 to 40 years; group 1, n = 8) subjects, were investigated. A single 2-g dose of ampicillin combined with 1 g of sulbactam in 60 ml of intravenous solution was administered to each subject over a 30-min period. Blood and urine samples were taken at baseline and serially over an 8.5-h period following the infusion. Ampicillin and sulbactam concentrations were assayed by high-performance liquid chromatography on a reversed-phase C-8 column. The mean levels in serum of both ampicillin and sulbactam were significantly higher for samples from group 3: for ampicillin from 1 through 8.5 h, and for sulbactam for the same time interval except at 5.5 h (P less than or equal to 0.05). The mean urinary excretion of both ampicillin and sulbactam was lowest, and urinary concentrations were highest in group 3. The areas under the serum drug concentration-time curve, the half-lives, and the maximum concentrations in serum were greatest, while the total clearance was lowest, for group 3 for both ampicillin and sulbactam. These results are consistent with a prolongation of antimicrobial activity of ampicillin-sulbactam in the elderly compared with that in younger subjects.

Patients with HIV infection pose a minimal but real risk to healthcare providers who sustain an exposure to such patients' blood or body fluids. Using data from large prospective studies, the estimated risk following parenteral exposure to HIV-positive blood is 0.4%. When a healthcare worker sustains an exposure, Mount Sinai Infection Control recommends immediate referral of the worker to an employee health service or emergency room for evaluation of the incident. Appropriate prophylaxis for hepatitis should be administered in a timely fashion. Counseling should be provided to exposed healthcare workers on the risk for HIV infection and precautions to take in the followup period. Zidovudine should be offered in a timely fashion as well; however, the ultimate decision on that treatment rests with the person exposed.

Twenty patients with adult-onset diabetes mellitus and malignant external otitis (MEO) were treated at the Mount Sinai Medical Center, New York, over a seven-year period (August 1976 to October 1983). A retrospective analysis compared patients who received an antipseudomonal cephalosporin as monotherapy (group A) with those who received conventional antipseudomonal therapy (group B). Pseudomonas aeruginosa was isolated in all patients. Differences (group B less than group A) included insulin dependence, underlying vascular disease, total number of cranial nerve palsies or paresis, and surgical procedures. The overall clinical outcome was similar in both groups; 64% of patients in group A (7/11) and 70% in group B (7/10) were cured at a follow-up period of five to 57 months. A more favorable outcome was found in patients with less extensive infection in both groups. Monotherapy compared favorably with conventional antipseudomonal therapy for the treatment of patients with MEO and moderate infection.

To determine the infectious complications associated with transhepatic biliary drainage devices, an analysis of the records of 38 patients who underwent placement of a pigtail catheter (n = 11), a Ring catheter/feeding tube (n = 13), or a Carey-Coons endoprosthesis (n = 15) was carried out. Nineteen infectious events occurred in 38 patients with 39 biliary devices. Infections consisted of bacteremia, cholangitis with and without documented bacteribilia, and intrahepatic abscesses and were frequently associated with obstruction (66.7 percent of infectious episodes). The most frequent organisms isolated from blood were Escherichia coli and Pseudomonas aeruginosa, and the most frequent organisms isolated from bile were P. aeruginosa, Klebsiella pneumoniae and Streptococcus faecalis. Trends for more frequent occurrence of neoplasms involving the gallbladder or biliary tract, recent surgical procedures and catheter manipulations in infected as compared with noninfected patients, and a delayed time to infection were noted in patients with an endoprosthesis.

Review of records of patients aged 65 years and older admitted to The Mount Sinai Hospital, New York, NY, during the period from 1970 through 1985 revealed 57 episodes of central nervous system infections, including 50 meningitides, 5 brain abscesses, 1 subdural empyema, and 1 epidural abscess. Predisposing conditions were present in 17 patients with meningitis, and concurrent infections occurred in 19 patients. Streptococcus pneumoniae accounted for 43% of all isolates; 25% were gram-negative organisms. Of the patients in this sample, fever was present in 100%, meningismus was present in 58%, and change in mental status was present in 86%. Sixty-five percent of patients with meningitis survived; increased mortality was associated with altered mental status, inappropriate initial antibiotic therapy, and hypoglycorrhachia. Delay in diagnosis, underlying disease, and bacteremia did not significantly alter outcome. All patients with focal infections presented with localizing signs and all survived.

Nine patients with malignant external otitis (MEO) were evaluated with Tc-99m bone scans, Ga-67 citrate scans, pluridirectional tomography, and computed tomographic (CT) scans in order to assess the role of each in the diagnosis and management of MEO. The Tc-99m and Ga-67 citrate scans were the most accurate studies in the initial identification of disease activity, while the return to normal or improvement of the Ga-67 citrate scan has been shown to correlate best with clinical resolution of MEO. CT demonstrated soft-tissue disease and central skull base osteomyelitis better than pluridirectional tomography. CT is excellent for localizing and following the progression of bone disease; however, because reossification of the skull base is a very slow process, CT cannot be used to follow accurately regression or inactivity of MEO affecting this area. CT is the best modality for following soft-tissue extension of MEO.

Twelve healthy ambulatory elderly subjects (mean age, 73-78 years) randomly received either a 4-g or 5-g dose of mezlocillin intravenously. One week later the regimen was repeated and patients crossed over to the other dose. Peak serum concentrations were 165 mg/L and 281 mg/L for the 4-g and 5-g doses, respectively. For both doses, differences in t1/2 beta (1.32 hr vs 1.13 hr), AUC (275 mg.hr/L vs 403 mg.hr/L), CL (207 mL/min vs 174 mL/min), CLR (59 mL/min vs 45 mL/min), CLNR (152 mL/min vs 130 mL/min) were not statistically significant. The differences in Varea (22.4L vs 168.8L, P less than or equal to .01) and Cmax (216.6 mg/L vs 317 mg/L, P less than or equal to .05) were statistically significant. Comparison with pharmacokinetic parameters obtained in younger subjects following the 5-g dose reveals that in the elderly the AUC, Varea, and CLNR are higher whereas the CL and CLR are lower. The elderly demonstrated an increase in nonrenal clearance compared with young subjects that is not fully compensatory. The increased AUC in the elderly group suggests that clinical studies examining mezlocillin doses and dose intervals in the treatment of serious infections are warranted in infected elderly patients.

Purpose: Bacteremia in the elderly is associated with a different clinical course and a higher mortality rate when compared with that in younger age groups. In order to examine these issues in the aged, we reviewed the clinical course and factors involved in the outcome of 100 episodes of bloodstream infections in patients over 65 years of age., Patients and Methods: The hospital records of all patients over 65 years of age at The Mount Sinai Hospital with a positive blood culture result during the period October 1984 to October 1986 were reviewed. Place of residence before hospital admission, site of acquisition of infection, source of bloodstream infection, and microorganism were analyzed. Antimicrobial therapy was defined as appropriate if initial therapy included one agent to which the isolate was sensitive, or inappropriate if the isolate was resistant. The following factors affecting survival were analyzed: age, sex, underlying diseases, clinical parameters on admission, white blood cell count, mental status, source of infection, microorganism isolated, antibiotic toxicity, and appropriate versus inappropriate antibiotic therapy., Results: Most patients were female (63 percent), were febrile (90 percent), had an altered mental status (52 percent), and had a neutrophilic response (61 percent). Eighty-three percent of patients were admitted from the community (home), 14 percent were from long-term-care facilities, and 3 percent were transferred from other hospitals. Fifty percent of infections were nosocomial, and 44 percent were community (home and nursing home)-acquired. Gram-negative organisms accounted for 60 percent of isolates, with Escherichia coli (22 percent) and Klebsiella species (11 percent) predominating; 30 percent were gram-positive organisms, with Staphylococcus aureus (13 percent) and Streptococcus faecalis (10 percent) the most common. The overall survival was 60 percent; the survival rate was 65.8 percent for community-acquired (home) bacteremia, 75 percent for nursing home-acquired bacteremia, and 52.8 percent for hospital-acquired bacteremia. Survival for gram-negative isolates was 65 percent, versus 51.7 percent for gram-positive isolates. Survival was greatest in patients whose source of bacteremia was either the genitourinary tract (70 percent) or an intravascular device (78 percent) and poorest in patients with lower respiratory tract source (42 percent); all three patients with endocarditis died. Increased survival was observed in patients treated with appropriate antimicrobial agents regardless of age, source of infection, or bloodstream isolates.(ABSTRACT TRUNCATED AT 400 WORDS)

Two groups of 10 healthy ambulatory subjects, i.e., a group of 10 persons less than or equal to 30 years of age (mean age, 27.6 years) and a group of 10 persons greater than or equal to 65 years of age (mean age, 70 years), were randomized in a single-trial crossover design to receive 1 and 2 g of cefoperazone with a 1-week washout between doses. The elderly subjects had both decreased estimated creatinine clearances and decreased albumin concentrations in serum. Cefoperazone concentrations in serum of elderly persons were significantly higher at each interval from 30 min to 6 h for the 2-g dose. Compared with that in younger persons, the total clearance in elderly subjects was significantly lower for both the 1- and 2-g doses, the renal clearance was significantly lower for the 2-g dose, and the area under the curve was significantly higher for the 2-g dose in the elderly persons. The half-life at beta phase was higher in the elderly persons at both the 1- and 2-g doses but not significantly so. Changes in total clearance and area under the curve and higher levels in serum in the elderly persons suggest a longer duration of antimicrobial activity in this age group.

In contrast to toxoplasmosis in non-AIDS immunocompromised hosts, AIDS patients rarely have been reported to be infected at extra-CNS sites. We report the case of a 45-year-old homosexual male with AIDS who presented with pneumonitis caused by Toxoplasma gondii following a previous illness consistent with CNS toxoplasmosis.

Thirteen patients with invasive infections of the external ear were treated with cefsulodin sodium. Eleven were elderly diabetic patients with malignant external otitis, and two were nondiabetic adults with cellulitis or chondritis of the external ear. Four of 11 patients with malignant external otitis had extensive disease, with progression of infection to the petrous apex, medial base of the skull, or parapharyngeal soft tissue. Eleven patients had granulation tissue in the external auditory canal, and three presented with cranial nerve palsies (V, VII, IX, X). Pseudomonas aeruginosa was isolated from all patients. Minimal inhibitory concentrations of cefsulodin for the strains isolated were 1.56-6.25 micrograms/ml (mean, 3.37 microliter/ml) and minimal bactericidal concentrations were 1.56-25 micrograms/ml (mean, 5.59 micrograms/ml). Duration of therapy was from one to 12 weeks. Nine patients had a positive clinical response, three had recurrent disease after initial improvement, and one was lost to follow-up. A positive response was correlated with a longer duration of therapy and less extensive disease; complications were minor. Cefsulodin appears to be an effective agent for the treatment of selected patients with invasive external otitis.