Development of minimum criteria for the initiation of antibiotics in residents of long-term-care facilities: results of a consensus conference.

Establishing a clinical diagnosis of infection in residents of long-term-care facilities (LTCFs) is difficult. As a result, deciding when to initiate antibiotics can be particularly challenging. This article describes the establishment of minimum criteria for the initiation of antibiotics in residents of LTCFs. Experts in this area were invited to participate in a consensus conference. Using a modified delphi approach, a questionnaire and selected relevant articles were sent to participants who were asked to rank individual signs and symptoms with respect to their relative importance. Using the results of the weighting by participants, a modification of the nominal group process was used to achieve consensus. Criteria for initiating antibiotics for skin and soft-tissue infections, respiratory infections, urinary infections, and fever where the focus of infection is unknown were developed.

PBMCs from both atopic asthmatic and nonatopic children show a TH2 cytokine response to house dust mite allergen.

BACKGROUND: The hypothesis that in atopic diseases the T-helper response is skewed toward a T(H)2-type cytokine response was based on studies with mitogen stimulation, T-cell clones, or both. OBJECTIVE: Using primary cultures, we investigated (1) whether atopic asthmatic patients have a T(H)2 response and nonatopic subjects have a T(H)1 response to allergen and (2) whether atopic patients have a decreased ability to mount T(H)1 immune responses to mycobacterial antigens. METHODS: The responses of PBMCs to allergen (house dust mite [HDM]) or purified protein derivative of Mycobacterium tuberculosis (PPD) stimulation from 10 severely and 14 moderately asthmatic patients (all allergic to HDM) were compared with those of 17 nonatopic healthy black (Xhosa) children. RESULTS: HDM-stimulated proliferation, IL-5 release, and the IL-5/IFN-gamma ratio were significantly increased in subjects with atopic asthma, whereas IFN-gamma release was not significantly different. IL-4 levels were below the level of detection. PPD-stimulated proliferation, IL-5 release, IFN-gamma release, and the IL-5/IFN-gamma ratio were not significantly different among the groups. Each group had a significantly higher IL-5/IFN-gamma ratio in response to HDM than to PPD (a T(H)1 stimulus). CONCLUSION: Our study, which used primary cultures to investigate the hypothesis that nonatopic subjects have a T(H)1 response to allergens, indicates that HDM stimulates a T(H)2 cytokine response in both atopic and nonatopic subjects but that the response is enhanced in atopic patients. Our results with PPD suggest that normal and atopic asthmatic subjects can have a T(H)1 cytokine response to mycobacteria, but there is a subgroup of atopic subjects that have a T(H)2 response.

Reduced interferon-gamma but normal IL-4 and IL-5 release by peripheral blood mononuclear cells from Xhosa children with atopic asthma.

BACKGROUND: Allergic asthma is increasing in black South Africans, a cohort with inherently high basal IgE levels. Atopy has been linked to an excess of the T helper 2 cytokines IL-4 and IL-5 relative to the T helper 1 cytokine interferon-gamma (IFN-gamma); however, most studies have utilized T cell clones. Studies on peripheral blood mononuclear cells (PBMC) have shown decreased IFN-gamma release in patients with atopic dermatitis. It is uncertain whether this finding extends to atopic asthma. OBJECTIVES: To characterize cytokine release by mitogen-activated PBMC from Xhosa children and to investigate whether reduced IFN-gamma release is a feature of atopic asthma and whether there is a relationship between cytokine profiles and asthma severity. METHODS: Cytokine release and proliferation of phytohemagglutinin-stimulated PBMC from 10 patients with severe asthma and 14 patients with moderate asthma (highly allergic to house dust mites) and 17 healthy controls was assessed. Total serum, allergen-specific, and Ascaris-specific IgE was measured. RESULTS: Proliferation did not differ between the groups. The release of IFN-gamma was progressively decreased (and the IL-4/IFN-gamma ratio increased) in the groups with moderate or severe asthma. Tumor necrosis factor-alpha release was reduced, but IL-4, IL-5, and granulocyte-macrophage-colony stimulating factor release was unchanged. The presence of Ascaris-specific IgE did not influence the cytokine profiles. CONCLUSION: Our study extends the findings observed for other atopic disorders and suggests that defective IFN-gamma release is a generalized feature of atopic diseases. This study-the first to investigate both severe and moderate asthma, with the groups having similar atopic profiles-indicates that the extent of the defect in IFN-gamma release might be related to asthma severity.

Antimicrobial resistance in long-term-care facilities.

During the last quarter century, numerous reports have indicated that antimicrobial resistance commonly is encountered in long-term-care facilities (LTCFs). Gram-negative uropathogens resistant to penicillin, cephalosporin, aminoglycoside, or fluoroquinolone antibiotics and methicillin-resistant Staphylococcus aureus have received the greatest attention, but other reports have described the occurrence of multiply-resistant strains of Haemophilus influenzae and vancomycin-resistant enterococci (VRE) in this setting. Antimicrobial-resistant bacteria may enter LTCFs with colonized patients transferred from the hospital, or they may arise in the facility as a result of mutation or gene transfer. Once present, resistant strains tend to persist and become endemic. Rapid dissemination also has been documented in some facilities. Person-to-person transmission via the hands of healthcare workers appears to be the most important means of spread. The LTCF patients most commonly affected are those with serious underlying disease, poor functional status, wounds such as pressure sores, invasive devices such as urinary catheters, and prior antimicrobial therapy. The presence of antimicrobial-resistant pathogens in LTCFs has serious consequences not only for residents but also for LTCFs and hospitals. Experience with control strategies for antimicrobial-resistant pathogens in LTCFs is limited; however, strategies used in hospitals often are inapplicable. Six recommendations for controlling antimicrobial resistance in LTCFs are offered, and four priorities for future research are identified.

Implications of methicillin-resistant Staphylococcus aureus on nursing home practice.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is being isolated with increasingly frequency from nursing home patients. There is a limited choice of antibiotics available to treat infections caused by the organism. Control measures for nursing homes have not been well established. METHODS: Using the key words "methicillin," "homes for the aged," and "long-term care," and also using the text term "MRSA," the MEDLINE files were searched from 1966 to 1989 using a CD ROM system. Articles occurring subsequent to this search, until the manuscript was submitted, were accessed using a monthly update from the MEDLINE database using the same key words. RESULTS: MRSA prevalence rates as high as 34 percent have been reported from long-term care settings. Risk factors for developing MRSA include being sick, debilitated, and functionally impaired. Frequent use of antibiotics and invasive devices, such as catheters, are also identified risk factors. The implication of MRSA colonization on patient outcomes is not clear. Vancomycin remains the drug of choice for treating MRSA infections. Control measures include surveillance of new and established cases and the introduction of isolation procedures. Patients colonized with MRSA should not be refused admission to a nursing home because of their MRSA status. CONCLUSIONS: MRSA in nursing homes will continue to increase. There are resulting implications for patient care, health care costs, and admission and discharge policies. Research should first establish what effect MRSA colonization has on clinical outcomes in this setting and, if necessary, go on to develop clinical and cost effective methods of prevention and control.

Bacillus species isolates from cerebrospinal fluid in patients without shunts.

Of 849 CSF cultures done at Hartford Hospital, nine were positive for nonanthrax Bacillus species. Differentiation of true nonanthrax Bacillus species infection from contamination requires careful consideration of the clinical findings, the clinical course, and the laboratory data. In seven patients the nonanthrax Bacillus species represented contamination. In two patients the nonanthrax Bacillus species represented true infection. In one of these infected patients, nonanthrax Bacillus species complicated a cranial gun shot wound. Bacillus cereus meningitis developed in the second patient, a premature infant, following sepsis from a contaminated IV catheter. Nonanthrax Bacillus species, especially B cereus, can be resistant to penicillins and cephalosporins when nonanthrax Bacillus species infections are being treated, susceptibility testing should always be performed.

Characterization of the effects of serotonin on the release of [3H]dopamine from rat nucleus accumbens and striatal slices.

The effect of serotonin agonists on the depolarization (K+)-induced, calcium-dependent, release of [3H]dopamine (DA) from rat nucleus accumbens and striatal slices was investigated. Serotonin enhanced basal 3H overflow and reduced K+-induced release of [3H]DA from nucleus accumbens slices. The effect of serotonin on basal 3H overflow was not altered by the serotonin antagonist, methysergide, or the serotonin re-uptake blocker, chlorimipramine, but was reversed by the DA re-uptake carrier inhibitors nomifensine and benztropine. With the effect on basal overflow blocked, serotonin did not modulate K+-induced release of [3H]DA in the nucleus accumbens or striatum. The serotonin agonists, quipazine (in the presence of nomifensine) and 5-methoxytryptamine, did not significantly affect K+-induced release of [3H]DA in the nucleus accumbens. This study does not support suggestions that serotonin receptors inhibit the depolarization-induced release of dopamine in the nucleus accumbens or striatum of the rat brain. The present results do not preclude the possibility that serotonin may affect the mesolimbic reward system at a site which is post-synaptic to dopaminergic terminals in the nucleus accumbens.

Effect of chronic antidepressant treatment on noradrenergic modulation of [3H]dopamine release from rat nucleus accumbens and striatal slices.

Unlike desipramine, a potent blocker of noradrenaline uptake, the antidepressant drugs, mianserin and citalopram did not, after chronic administration (28 days), attenuate the clonidine-induced inhibition of [3H]dopamine (DA) release from rat nucleus accumbens slices. Mianserin, like desipramine, failed to alter the isoproterenol-induced enhancement of [3H]DA release from rat nucleus accumbens and striatal slices. These findings suggest that antidepressant action does not necessarily involve desensitization of central alpha 2- or beta-adrenoceptors which influence neuronal transmission.

Infections in the elderly.

Elderly patients appear to be predisposed to serious infections because of coexisting chronic or acute diseases that disrupt integumental barriers, impair clearance mechanisms, or compromise cellular responses to infection. The severely disabled elderly are particularly at high risk, because they are often unable to care for their personal hygiene and are malnourished, immobile, incontinent, or institutionalized. Senescence of the immune system per se does not appear to be a major predisposing factor for infection in this population. Infections in the elderly frequently present with non-specific signs and symptoms. Clues of focal infection are often absent or obscured by underlying chronic conditions. Once a site of infection is identified, clinicians should initiate therapy with broad-spectrum antibiotics to treat the array of most likely potential pathogens. Strategies to prevent infection include programs to help the elderly maintain active, non-institutionalized life-styles and the appropriate use of available vaccines.

Effect of chronic desipramine treatment on adrenoceptor modulation of [3H]dopamine release from rat nucleus accumbens slices.

The effects of alpha 2- and beta-adrenoceptor agonists on the 25 mM K+-induced release of [3H]dopamine [( 3H]DA) from the nucleus accumbens slices of chronic desipramine (DMI)- and saline-treated rats were investigated using a superfusion technique. The K+-induced release of [3H]DA from nucleus accumbens slices was shown to be Ca2+ dependent and to be enhanced by ascorbic acid. In experiments with isoproterenol, ascorbic acid was added to the superfusion media in order to prevent the otherwise rapid oxidation of the drug. The K+-induced release of [3H]DA from nucleus accumbens slices of saline-treated rats was significantly decreased by the alpha 2-adrenoceptor agonist, clonidine (10 microM; 89 +/- 2.4% of control values; P less than 0.002), and significantly enhanced by the beta-adrenoceptor agonist, isoproterenol (1 and 10 microM; 122 +/- 4.3 and 171 +/- 2.9% of control values, P less than 0.002 and P less than 0.001, respectively). The basal release of [3H]DA was strongly enhanced by 10 microM but not 1 microM isoproterenol. Chronic DMI pretreatment (10 mg/kg i.p. for 28 days) did not significantly alter the K+-induced release of [3H]DA. Chronic DMI treatment attenuated the alpha 2-adrenoceptor-mediated inhibition of [3H]DA release, while the beta-adrenoceptor-mediated stimulation remained unchanged. The net effect of chronic DMI treatment therefore would appear to be a facilitation of dopaminergic neurotransmission in the mesolimbic system. This is consistent with behavioural evidence which suggests that the function of the mesolimbic dopaminergic reward system is facilitated by chronic treatment with antidepressant drugs.

Alpha 2 and beta-adrenoceptor agonists modulate [3H]dopamine release from rat nucleus accumbens slices: implications for research into depression.

The modulatory effects of noradrenergic agonists on the 25 mM K+-induced release of [3H]dopamine (3H-DA) from rat brain nucleus accumbens slices was investigated, using a superfusion technique. The K+-induced release of 3H-DA was Ca2+ dependent, significantly enhanced (25-32%; p less than 0.02) by the beta-adrenoceptor agonist isoproterenol (10 microM), and significantly decreased (13-25%; p less than 0.05) by the alpha 2-adrenoceptor agonist clonidine (10 microM). At these concentrations neither drug affected basal release of 3H-DA. Clonidine (100 microM) increased the basal release of 3H-DA, while decreasing the K+-induced release by 19% (p less than 0.01). The inclusion of desipramine in the incubation medium, to prevent accumulation of 3H-DA into noradrenergic neurons, did not alter the inhibitory effect of clonidine (10 microM) on 3H-DA release. This study provides direct evidence that noradrenergic neurons can modulate dopaminergic neurotransmission in the mesolimbic system.