Understanding, predicting and controlling the emergence of drug-resistant tuberculosis: a theoretical framework.

The high prevalence of tuberculosis in developing countries and the recent resurgence of tuberculosis in many developed countries suggests that current control strategies are suboptimal. The increase in drug-resistant cases exacerbates the control problems. Currently employed epidemic control strategies are not devised on the basis of a theoretical understanding of the transmission dynamics of Mycobacterium tuberculosis. We describe and discuss a theoretical framework based upon mathematical transmission models that can be used for understanding, predicting, and controlling tuberculosis epidemics. We illustrate how the theoretical framework can be used to predict the temporal dynamics of the emergence of drug resistance, to predict the epidemiological consequences of epidemic control strategies in developing and developed countries, and to design epidemic control strategies.

HIV risks in the health care organization.

Health-care workers who sustain an accidental parenteral exposure to HIV are at risk of infection. Although only incomplete data are available to assess the risk, these data are reassuring. The most important lesson for health-care workers in the AIDS era is that nearly all risky exposures can and should be prevented. Greater emphasis on needlestick safety, control of infection in high-risk environments and improved devices and procedures can alleviate the vast majority of hazardous exposures.

Does knowledge of human immunodeficiency virus infection decrease the frequency of occupational exposure to blood?

Implementation of universal precautions is advocated to prevent exposure to human immunodeficiency virus (HIV) and other bloodborne pathogens. Critics of this approach argue that additional benefit can be derived by identifying and labeling patients known to be infected. Knowledge of HIV infection status could result in a reduced exposure rate by two mechanisms: (a) by motivating improved compliance with universal precautions, or (b) by allowing changes in procedure or technique not feasible for all patients. Compliance with universal precautions may reduce the frequency of some types of exposure but has not been associated with a reduction in the frequency of needlestick exposures in several studies. Despite the perception by some health care workers that awareness of HIV status will result in improved safety, no objective data have demonstrated a direct benefit from testing or identifying infected patients. Health care workers who recognize the presence of occupational HIV risk are apt to be motivated to practice universal infection control precautions and experience little additional benefit from testing individual patients. Health care workers in low prevalence areas may experience less incentive to comply routinely with universal precautions and selectively may be motivated when HIV infection is diagnosed in individual patients. However, routine testing in areas of low HIV prevalence is not likely to be cost effective. Until further research clarifies the efficacy and costs of universal precautions or HIV testing, infection control standards should maximize local autonomy in developing rational policies consistent with institutional needs.

Efficacy of ciprofloxacin in animal models of infection: endocarditis, meningitis, and pneumonia.

Animal models of infection are very useful tools for identifying those situations in which antibacterial drugs, including the quinolones, may play special roles, i.e., for positioning a drug correctly for its role in the treatment of human disease. Ciprofloxacin has been studied extensively in discriminative animal models of infection, and its efficacy in the treatment of these infections has been compared with that of standard therapy. In a rabbit model of staphylococcal endocarditis, ciprofloxacin was as effective as nafcillin alone, as well as nafcillin and gentamicin in combination, in treating rabbits with methicillin-susceptible Staphylococcus aureus endocarditis. Additionally, its activity was equal to that of vancomycin in reducing vegetation titers in rabbits with methicillin-resistant staphylococcal endocarditis. In a rabbit model of pseudomonal meningitis, ciprofloxacin was as effective as the combination of ceftazidime and tobramycin in lowering bacterial titers. However, in this model, serum levels of ciprofloxacin (6 micrograms/ml) necessary to achieve a bactericidal effect in the cerebrospinal fluid were slightly higher than levels targeted for humans. In a model of pseudomonal pneumonia in neutropenic guinea pigs, the efficacy of ciprofloxacin was compared with that of tobramycin and ceftazidime, both alone and in combination: ciprofloxacin was as effective in lowering bacterial counts as was the combination of ceftazidime plus tobramycin and its activity was superior to that of either drug alone. Thus, data from studies of ciprofloxacin in the treatment of endocarditis, meningitis, and pneumonia in animal models of infection suggest that this quinolone may play an important role in the therapy of these difficult-to-manage infections in humans.

Occupational exposure to HIV: frequency and rates of underreporting of percutaneous and mucocutaneous exposures by medical housestaff.

PURPOSE: To study the frequency of work-related exposures to human immunodeficiency virus (HIV)-infected blood and reporting of exposures among medical housestaff. SETTINGS: Three teaching hospitals where HIV infection is prevalent among patients. SUBJECTS: Internal medicine interns and residents in training in 1988-1989. METHODS: In a cross-sectional survey, house officers were asked to complete anonymously a questionnaire reviewing their past percutaneous and mucocutaneous exposure to blood products. RESULTS: Nineteen percent of the respondents (16 of 86) recalled accidental exposure to HIV-infected blood, and 36% (31 of 86) recalled exposure to blood from patients at high risk for having HIV infection. Of the exposures recalled in the 12 months prior to the survey, 81% (47 of 58) of all needlestick injuries and all (nine of nine) needlestick injuries from HIV-infected blood occurred in postgraduate year 1 or 2 trainees. Only 30% (31 of 103) of the needlestick injuries recalled by subjects were reported. The principal reasons for not reporting were time constraints, perception that the percutaneous injury did not represent a significant exposure, lack of knowledge about the reporting mechanism, and concern about confidentiality and professional discrimination. CONCLUSIONS: Medical housestaff are at substantial risk for occupational infection with HIV. A large proportion of internal medicine housestaff recall accidental exposure to blood during medical school and residency, and the majority of exposures were not reported. Hospitals may be able to increase rates of reporting of percutaneous exposures to HIV by developing programs that are easy to access, efficient, and strictly confidential.

Postexposure prophylaxis for human immunodeficiency virus (HIV) infection following sexual assault.

Although the 1998 Centers for Disease Control and Prevention's guidelines for treatment of sexually transmitted diseases recommend offering postexposure prophylaxis for human immunodeficiency virus (HIV) infection following sexual assault, there are no detailed protocols on how to provide this treatment. Postexposure prophylaxis has been shown to lower the risk of seroconversion following occupational exposure to HIV by 81%, but has not yet been evaluated following sexual exposure. Though scientific data are limited, victims of sexual assault should be given the best information available to make an informed decision regarding postexposure prophylaxis. When the choice is made to take medications to prevent HIV infection, treatment should be initiated as soon as possible, but no later than 72 hours following the assault, and should be continued for 28 days. HIV postexposure prophylaxis should be provided in the context of a comprehensive treatment and counseling program that recognizes the physical and psychosocial trauma experienced by victims of sexual assault.

Current epidemiologic evidence and case reports of occupationally acquired HIV and other bloodborne diseases.

Studies in which noninfected persons shared households with human immunodeficiency virus (HIV)-infected family members and friends, and had substantial though non-sexual contact with them revealed no transmissions of the HIV virus. These results suggest a similar low risk for healthcare workers, particularly those who have little or no contact with blood. However, occupational transmission of HIV, when it does occur, is most commonly caused by needlestick injuries. Nurses make up the largest group--nearly 80%--of hospital workers who contract HIV infection on the job. Generally, the risk ratio following an HIV needlestick is 1 in 250. Improper needle disposal, recapping and other ingrained behavior patterns are typical causes of needlestick accidents. Though the focus today is on HIV/acquired immunodeficiency syndrome (AIDS), it is important to realize that hepatitis B accounts for 200 to 300 deaths a year among healthcare workers. Awareness of the risk of needlestick injuries, and the considerable financial and emotional costs they can impose, should justify preliminary expenditures on needlestick prevention programs.

Nosocomial transmission of opportunistic infections.

Immunocompromised patients are at high risk for opportunistic infections. Traditionally, these infections were thought to arise from endogenous reactivation of previously acquired latent infections, and nosocomial transmission therefore was deemed to be so unlikely that no special infection control interventions were needed to prevent transmission in healthcare settings. However, new data have challenged this view and suggest that some opportunistic pathogens are transmissible from one immunosuppressed patient to another. Epidemiological investigations, molecular genotyping, animal studies, and air-sampling experiments lend support to the hypothesis that reinfection with opportunistic pathogens does occur, that airborne transmission is possible, and that nosocomial spread is a plausible explanation for case clusters. Taken together, these observations support the view that some opportunistic infections are exogenous in origin and that additional epidemiological investigations are needed to define the true risk of nosocomial spread and need for isolation.

Risky business: using necessarily imprecise casualty counts to estimate occupational risks for HIV-1 infection.

Although the genesis of healthcare worker anxiety regarding occupational risks of HIV-1 infection is clear, the reasons for continued insistence on a meticulous "casualty count" become less clear with time. One could, in fact, argue that the precise number of such infections has become virtually meaningless, because the routes of occupational/nosocomial transmission of HIV-1 and the magnitude of risk for infection following an adverse exposure in the healthcare setting have been well-characterized. Nevertheless, with the substantial limitations of these data clearly in mind, we have summarized the numbers of healthcare workers reported to have HIV-1 infection in each of the above categories in Table 2. The likelihood that an individual case represents true occupational infection decreases as one moves down the table. Having waded through the depths of this literature, we have reached the conclusion that, of the available data, the magnitude of risk for occupational HIV-1 infection remains the single most useful and instructive statistic available. Longitudinal cohort studies of HCWs involved in the day-to-day care of HIV-1-infected patients and in the handling and processing of specimens from such patients provide the best available evidence regarding the magnitude of risk for transmission of this virus in the healthcare setting. Fourteen prospective studies are currently in progress, with approximately 2,000 HCWs enrolled (Table 4). Six HCWs enrolled in these studies have developed serologic evidence of HIV-1 infection following percutaneous exposures, yielding an infection rate per participant of 0.32% and an infection rate per exposure of 0.31%.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical infection control in gene therapy: a multidisciplinary conference.

Gene therapy is being studied for the treatment of a variety of acquired and inherited disorders. Retroviruses, adenoviruses, poxviruses, adeno-associated viruses, herpesviruses, and others are being engineered to transfer genes into humans. Treatment protocols using recombinant viruses are being introduced into clinical settings. Infection control professionals will be involved in reviewing the safety of these agents in their clinics and hospitals. To date, only a limited number of articles have been written on infection control in gene therapy, and no widely available recommendations exist from federal or private organizations to guide infection control professionals. The goals of the conference were to provide a forum where gene therapy experts could share their perspectives and experience with infection control in gene therapy and to provide an opportunity for newcomers to the field to learn about issues specific to infection control in gene therapy. Recommendations for infection control in gene therapy were proposed.

Procedure-specific infection control for preventing intraoperative blood exposures.

Contemporary intraoperative infection control must address the risk of infection transmission to both patients and their providers. The patient must be protected from intraoperative wound contamination and exposure to blood-borne pathogens during procedures. Providers must be protected from injuries and mucocutaneous exposure to the patient's blood. Procedure-specific infection control precautions, or similar strategies that address this bidirectional potential for infection transmission, may prove successful in accomplishing improved safety for all.

Occupational health issues for providers of care to patients with HIV infection.

The perception that HIV is a highly contagious nosocomial pathogen persists despite a great deal of evidence to the contrary. However, health care workers are at a low but finite risk of occupational infection with the virus, particularly through accidental needle-stick inoculations with infected blood. Universal blood and body fluid precautions minimize the risk of nosocomial transmission of a variety of pathogens, including HIV, and should be routinely employed by all health care workers for all patients.

Risks to health care workers from occupational exposure to hepatitis B virus, human immunodeficiency virus, and cytomegalovirus.

Transmission of hepatitis B, HIV-1 and CMV by percutaneous, mucosal, or contact with intact skin is of concern to health care personnel. This article summarizes current information regarding the risks of transmission of these agents and emphasizes infection control measures.

Extended-spectrum beta-lactamase-producing Klebsiella pneumoniae in a neonatal intensive care unit: risk factors for infection and colonization.

An outbreak of extended spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBLKp) infections in a neonatal intensive care unit (NICU) prompted a prospective investigation of colonization and infection with this pathogen. From August 1, 1997 to May 30, 1999, neonates admitted to the NICU for more than 24 h were screened for ESBLKp acquisition. Neonatal gastrointestinal screening was performed by means of faecal sampling within 48 h of admission and then weekly until discharge. Isolates were typed using pulsed-field gel electrophoresis (PFGE). Time-dependent proportional hazard models were used to identify independent effects of invasive procedures and antimicrobials after controlling for duration of stay at the NICU. During the study period, 464 neonates were admitted and 383 were regularly screened. Infections occurred in 13 (3.4%) neonates and 206 (53.8%) became colonized. Independent risk factors for colonization during the first nine days in the NICU were the antimicrobial combination cephalosporin plus aminoglycoside [hazard rate (HR)=4.60; 95% CI: 1.48-14.31], and each NICU-day was associated with a 26% increase in the hazard rate for colonization (HR=1.26; 95% CI: 1.16-1.37). Previous colonization (HR=5.19; 95% CI: 1.58-17.08) and central vascular catheter use (HR=13.89; 95% CI: 2.71-71.3) were independent risk factors for infection. In an outbreak setting the proportion of neonates colonized with ESBLKp was observed to increase with the duration of stay and antimicrobial use, and once colonized, infants exposed to invasive devices may become infected.

Are universal precautions realistic?

In concluding whether universal precautions are necessary, it certainly appears that we need something to reduce the significant problem of HIV transmission to health-care providers. As occupational risk goes, it exceeds the occupational risk of a number of other high-risk professions. Unfortunately, we do not know if universal precautions are effective. We also do not know the true compliance rate in use of universal precautions, nor whether they have an impact on transmission even if effectively used. What are the alternatives? They are not great, but some have not been adequately explored or implemented. Re-engineering around needle use in the hospital is clearly the most likely area to produce concrete results, because needlesticks are overwhelmingly the greatest source of infection, but this has not been encouraged to the degree it could be, even with systems already developed. Universal testing does not appear to be a viable alternative, for numerous reasons already discussed. Finally, are universal precautions more important for other pathogens than HIV? I would say yes. Hepatitis B, hepatitis C, and nosocomial infections are more important both as public health issues and as health-care provider prevention issues. If universal precautions are effective in reducing any of these, they are worthwhile.

Hand protection.

The traditional purpose of surgical gloves is to prevent transmission of pathogens (usually bacterial) from surgeon to patient. Yet the hand is also the most common site of injury and blood contamination among operating room personnel. Thus, gloves also can protect against transmission of pathogens from patient to surgeon. This article focuses on the value of gloves for hand protection. The current data on such protection derive exclusively from studies that use glove leak and contamination as outcome measures. There are no data that measure protection in terms of actual disease transmission.

The risk for otolaryngologists who treat patients with AIDS and AIDS virus infection: report of an in-process study.

The risk of contracting acquired immune deficiency syndrome (AIDS) is a concern to otolaryngologists and other health care workers. Failure to appreciate this valid concern is dangerous, but overestimating it may be equally injurious to the delivery of good patient care. We review the data on antibody titers and recovery of cultured virus in blood, saliva, middle ear fluid, cerumen, tears, and nasal mucous. We also report the initial findings of a prospective study of otolaryngologists at the San Francisco General Hospital. It appears that the risk of transmission of AIDS is low and can be minimized by sound infection control measures similar to those for hepatitis B.

Post-exposure prophylaxis for HIV.

The advent of preventive treatment for HIV highlights the urgent need for basic, clinical, and epidemiologic research targeting the pathogenesis and prevention of cutaneous and mucosal infection. In addition, the impact of HIV prophylaxis on the frequency of risk behaviors and antiretroviral drug resistance, especially in cities with high HIV prevalence, must be evaluated. In our view, the available data (albeit not definitive) are strong enough to support the provision of post-exposure prophylaxis in select cases of sexual and injection drug use exposure in addition to occupational exposures. However, post-exposure treatment should be used judiciously and only in the context of a comprehensive prevention program. Ultimately, primary exposure prevention, whether in health care facilities or in the community, is the most important strategy to prevent AIDS.

Transmission of HIV in health care workers.

Health care workers may be occupationally exposed to human immunodeficiency virus (HIV). The risk of infection is highest with accidental needlestick and similar percutaneous exposures. Emphasis should be placed on avoiding this type of accident. Strategies to prevent accidents and to manage exposures once they have occurred should be developed in each work environment. It is to be hoped that a combination of better infection control, safer devices and technologies, and postexposure prophylaxis with zidovudine (AZT) or other chemotherapeutic agents will help prevent infection in health care providers caring for HIV-infected patients.

Accidental exposures to blood and body fluids among health care workers in dental teaching clinics: a prospective study.

The authors evaluated accidental exposures to blood and body fluids reported to a hotline or to health officials at four dental teaching clinics. The authors used a standard questionnaire to solicit and record data regarding each exposure. During a 63-month period, 428 parenteral exposures to blood or body fluids were documented. Dental students and dental assistants had the highest rates of exposure. Syringe needle injuries were the most common type of exposure, while giving injections, cleaning instruments after procedures and drilling were the activities most frequently associated with exposures.