Methylene Blue--a therapeutic dye for all seasons?

Since it was first synthesised in 1876, Methylene Blue (MB) has found uses in many different areas of clinical medicine, ranging from dementia to cancer chemotherapy. In addition, MB formed the basis of antimicrobial chemotherapy--particularly in the area of antimalarials--and eventually led to the discovery of the neuroleptic drug families. More recently, the photosensitising potential of MB and its congeners has been recognised, and these are being applied in various antimicrobial fields, especially that of blood disinfection. The range of activities of MB is due to the combination of its simple chemical structure and facility for oxidation-reduction reactions in situ.

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.

Serum cytokine levels in patients with Alzheimer's disease.

Alzheimer's disease (AD) has been proposed to be an inflammatory disorder. In a recent study, markedly elevated levels of the anti-inflammatory cytokine transforming growth factor beta (TGF-beta) in the serum and cerebrospinal fluid of patients with advanced AD suggested a potential predictive value of this cytokine in patients with AD. In the present prospective study, we tested the hypothesis that the levels of TGF-beta in serum would be increased in patients with AD and could thereby serve as a diagnostic marker. We found that serum TGF-beta levels but not proinflammatory cytokine levels were significantly (P < 0.05) elevated in patients with AD (n = 22) in comparison with the levels in their healthy spousal controls. Also, serum TGF-beta levels were positively correlated (r = 0.45; P < 0.05) with disease severity. Nevertheless, the elevation in serum TGF-beta levels in patients with Ad was modest, and considerable overlap with the control values suggests that the diagnostic usefulness of this cytokine for AD is limited.

Dynamics of coagulase-negative staphylococcal colonization in patients and employees in a surgical intensive care unit.

Because there is little information about the frequency of carriage of various species of coagulase-negative staphylococci (CNS) in hospital staff, we prospectively investigated nasal CNS in patients and personnel in a Surgical Intensive Care Unit (SICU). The majority of CNS from personnel were Staphylococcus epidermiditis. The CNS species from patients on admission were more diverse and included multiply antibiotic-resistant S. haemolyticus. Patients' CNS became more like CNS colonizing personnel after admission with respect to both antimicrobial susceptibility and speciation. Plasmid and antibiotic sensitivity profiles of S. epidermidis resistant to multiple antibiotics from five patients were identified as those from one employee, but there was no evidence that this was of clinical significance. A variety of factors influence nasal colonization by CNS in SICUs. The nasal CNS of patients change after admission and may become more resistant and less diverse. The factors influencing changes in the antibiotic susceptibility and the aetiology of CNS infection require further study.

Amantadine-resistant influenza A in a nursing facility.

Rapid index case treatment and amantadine prophylaxis were implemented in two nursing homes exposed to influenza A. Facility A had no isolation of cases, and 18 of 22 cases occurred after amantadine hydrochloride therapy was initiated. Three patients exhibited amantadine-resistant virus. Facility B had day 1 isolation of the index case. A facility-wide outbreak did not occur. The experience of these facilities suggests that concurrent amantadine treatment and prophylaxis without adequate case isolation may promote further influenza A infection in a nursing facility.

Suboptimal effect of daptomycin in the treatment of bacteremias.

We have reported two cases involving bacteremic patients who failed to respond adequately to the investigational agent daptomycin. Despite apparent sensitivity of the organisms, therapy was unsuccessful in both patients using the recommended dosage. The sponsor of daptomycin is currently reevaluating the recommendation and may be revising their dosage guidelines in the future.

The influence of serum albumin and alpha 1-acid glycoprotein on vancomycin protein binding in patients with burn injuries.

Ten patients with burn injuries (mean total body surface area burn = 29% +/- 16) were studied at various points in the course of their burn therapy. Alpha 1-Acid glycoprotein, albumin, and vancomycin concentrations were determined with either a trough or peak vancomycin quantitative determination. Alpha 1-Acid glycoprotein concentrations ranged from 125 to 333 mg/dl and albumin concentrations ranged from 1.7 to 4.2 gm/dl. Vancomycin protein binding, as determined by ultrafiltration, averaged 29% +/- 6%. There was a strong (r = 0.92) relationship between percent protein-bound vancomycin and albumin. There was a poor statistical relationship between percent protein-bound vancomycin and alpha 1-acid glycoprotein (r = 0.28). Alpha 1-Acid glycoprotein appeared to have virtually no effect on the protein-binding characteristics of vancomycin over the range of concentrations studied.

Nursing home-acquired pneumonia.

Pulmonary infection acquired in nursing homes has not been extensively studied. Those data that have been published about the frequency and nature of nursing home-associated pneumonias are reviewed here. It remains unclear whether or not these institutionally-acquired pneumonias differ significantly from those that would occur in an age-matched control group with community-acquired infection. Viral pneumonias are recognized as significant causes of morbidity in the elderly.

Current immunization practices. 1. Polio, diphtheria, tetanus, pertussis, measles, mumps, rubella, and influenza.

When used appropriately, immunization can effectively prevent many infections and diseases. Some vaccines, such as that for polio, are believed to produce lifelong immunity. Others, such as those for tetanus and diphtheria, may require that a booster injection be given upon exposure to assure full immunity. Still others, such as that for influenza, confer immunity for only a limited time. Inoculation is not without risk, particularly in immunosuppressed, allergic, febrile, or pregnant patients. However, in otherwise healthy patients, serious sequelae are so rare that they are far overshadowed by the enormous benefits of immunization.

Simulation of vancomycin peak and trough concentrations using five dosing methods in 37 patients.

Five methods of dosing vancomycin (Matzke, Moellering, Nielsen, Lake-Peterson, and manufacturer's) were simulated in 37 patients. Ten serum samples were obtained after a 1-hour intravenous infusion of 6.2-20 mg/kg total body weight. A preinfusion serum sample was obtained from patients not studied on the first dose. Initial estimates of pharmacokinetic values were made using nonlinear iterative least squares regression and serum concentration-time data. These data were fitted to a two-compartment, open-infusion model. Simulations of the peak and trough serum concentrations at steady state for each patient were determined by multiple-dose simulated pharmacokinetics and each patient's pharmacokinetic values using the regimen suggested by each of the five methods. Steady-state serum concentrations, predicted systemic clearance by each method (except Lake-Peterson), and the daily dose for each patient recommended by each method were determined. All the methods underpredicted actual drug clearance, with the Nielsen method having the lowest prediction. The Matzke method recommended the largest dosage. Using each of the methods, only 3-16% of patients would have achieved recommended peak and trough serum concentrations. In the simulation model used, no method performed satisfactorily in attaining the desired vancomycin peak and trough concentrations. We suggest that the Lake-Peterson method could be used initially, provided that monitoring is also performed to adjust the dosage regimen further.

Vancomycin pharmacokinetics in patients with various degrees of renal function.

The influence of age, protein binding, and renal function on the pharmacokinetics of intravenous vancomycin was evaluated in 37 adult patients with various degrees of renal function. Patients were categorized into three groups based on measured creatinine clearance (CLCR): groups 1, 2, and 3 had 24-h CLCRs of greater than 70, 40 to 70, and 10 to 39 ml/min per 1.73 m2, respectively. After 1 h of intravenous infusion, concentrations of vancomycin in serum declined in a biexponential manner in all patients. Diminished renal function in groups 2 and 3 was accompanied by a lower total body vancomycin clearance (CL) (52.6 and 31.3, respectively, versus 98.4 ml/min per 1.73 m2) and a lower renal vancomycin clearance (CLR) (48.2 and 19.8, respectively, versus 88.0 ml/min per 1.73 m2) than in group 1. No significant differences in apparent distribution volume of the central compartment or apparent distribution volume at steady state were observed. Mean serum protein binding of vancomycin was 30% and was not significantly affected by renal function. Stepwise multiple linear regression analysis revealed that CLCR was the strongest predictor of vancomycin CL (r = 0.77, P less than 0.001) and vancomycin CLR (r = 0.87, P less than 0.001). Age did not significantly improve these correlations once CLCR was included. The relationship of vancomycin CL and CLCR was utilized to develop the following equation to dose vancomycin in the majority of renally impaired patients: dose (milligrams per kilogram per 24 h) = 0.227CLCR + 5.67, where CLCR is standardized to milliliters per minute per 70 kg. The practical dosing intervals that the calculated dose can be divided into and administered include 8, 12, 24, and 48 h based on the CLCR of the patient.

Penicillin-resistant Streptococcus pneumoniae. Report of a case and results of a clinical laboratory proficiency survey in Minnesota.

An elderly woman with Streptococcus pneumoniae meningitis relatively resistant (minimum inhibitory concentration, [MIC] = 0.12 micrograms/mL) to penicillin is reported. The occurrence of penicillin-resistant pneumococcal infections is reviewed and management discussed. Because of the importance of recognition of resistant pneumococci, a state-wide clinical laboratory survey was conducted to determine the accuracy of susceptibility testing for this isolate. Of 111 laboratories completing the survey, only 26 performed the 1-microgram oxacillin disk test as recommended by the National Committee for Laboratory Standards (NCCLS). When laboratories were analyzed according to hospital size, the proficiency in performing the proper susceptibility testing was 55% (6 of 11) for hospitals with more than 400 beds versus 3% (2 of 58) for hospitals with fewer than 100 beds (P less than 0.0001 by Fisher's exact test). This contrasts with reported surveys by the College of American Pathologists (CAP), and reasons for this are explored. Guidelines for laboratory testing of S. pneumoniae are reviewed, and additional study of clinical proficiency with attention to laboratory size is recommended.

Vancomycin-induced neutropenia during treatment of osteomyelitis in an outpatient.

A case of vancomycin-associated neutropenia occurring during long-term outpatient therapy with vancomycin is described. Pharmacokinetic studies demonstrated that the patient's vancomycin serum levels were within an acceptable range during treatment. Eighteen other reported cases of vancomycin-associated leukopenia are discussed in brief. An immunologic mechanism has been proposed but a clear understanding is lacking. Patients receiving long-term vancomycin therapy should have their white blood cell counts periodically monitored.

Infection control practices in Minnesota nursing homes.

Because infection is a major cause of hospitalization among nursing home residents, we assessed infection control activities and related employee health policies in Minnesota nursing homes, using a questionnaire. The majority of institutions (378/440, 85.9%) responded. We found traditional isolation techniques were widely used, but blood and urine precautions were employed in less than half of the homes. Infection surveillance tended to focus on chart review. Antibiotic utilization studies were done in 76% of homes. Procedures for urinary catheter care were often at variance with current recommendations. Employee health policies required a physical examination of a new employee in a minority of institutions. Policies required by Minnesota statute (eg, skin testing for tuberculosis and documentation of employee illness) were carried out by most institutions. Infection control policies and procedures in nursing homes should be redefined so that, where appropriate, they are more consistent with practices in acute-care hospitals.

Colonization of hospitalized patients by Staphylococcus aureus, Staphylococcus epidermidis and enterococci.

Patients admitted to a medical intensive care unit (29), a surgical intensive care unit (29) and a general medical ward (34) were studied to determine the frequency of colonization by Staphylococcus aureus, Staph. epidermidis and enterococci. Cultures of anterior nares, pharynx, axilla, periurethral tissues, and rectum were done within 24 h of admission and every 48-72 h thereafter for the duration of hospitalization. We found Staph. aureus colonization of pharynx, axilla, periurethral tissues and rectum to be equally frequent in patients with and without nasal colonization. Staphylococcus epidermidis was commonly recovered from all sites except the pharynx. The 49 strains of this organism acquired in the hospital were significantly more often resistant to nafcillin, cephalothin, chloramphenicol, trimethoprim-sulfamethoxazole and gentamicin than were 199 isolates recovered from patients at the time of admission. Enterococci were commonly isolated from rectal swabs and, less often, from other sites. Acquisition of enterococcal colonization during hospitalization was correlated significantly with antibiotic administration.