Ampicillin and an ester in experimental Hemophilus influenzae meningitis.

A new methoxymethyl ester of hetacillin is highly lipid-soluble, a property which was expected to enhance its penetration into the central nervous system (CNS). We compared the penetration of the ester and ampicillin into the cerebrospinal fluid (CSF) of normal rabbits and those with experimental Hemophilus influenzae meningitis. In normal rabbits treated by constant intravenous infusion, mean per cent penetration (see article) of the ester was four times as great as that of ampicillin (6.6 +/- 3.7% against 1.6 +/- 1.9%), and the difference in CSF drug levels attained was accentuated when bolus IV infusion was used. Drug concentration in brain tissue was three times as great in a rabbit treated with the ester (0.79 mug/gm against 0.26 mug/gm). In rabbits with meningitis, the ester again achieved higher CSF concentrations. Per cent penetration into CSF in infected rabbits was 23% for the ester and 13% for ampicillin. Bactericidal activity of the drugs was comparable; over 8 hr of treatment both drugs significantly reduced the CSF bacterial titers of infected animals. Our data demonstrated that the ester enters the CSF and CNS in higher concentration than ampicillin, with no loss in bactericidal activity.

The burden of infection in long-term care.

Available data, although fragmentary, indicate that infections impose a large burden on long-term-care facilities (LTCFs) in the United States. Endemic infections occur with frequencies estimated to range between 1.64 and 3.83 million per year. These estimates rival or exceed the annual tally for nosocomial infections in acute-care settings. Infections associated with outbreaks caused by respiratory, gastrointestinal, and antimicrobial-resistant pathogens burden LTCFs even further. As judged by antimicrobial use, transfers to hospital, and mortality figures, infections in LTCFs are not trivial. Moreover, annual costs associated with these infections appear to exceed $1 billion. Recognition of the burden associated with infection in LTCFs helps to identify research priorities for this rapidly growing area of healthcare.

Methicillin-resistant Staphylococcus aureus in a nursing home and affiliated hospital: a four-year perspective.

OBJECTIVES: To determine the effect of a methicillin-resistant Staphylococcus aureus (MRSA) outbreak in a nursing home on the subsequent MRSA caseload in a closely affiliated hospital. DESIGN: Observational and descriptive; routine and special MRSA surveillance data for nursing home and hospital were reviewed for a four-year period (1988 to 1991) as were records regarding patient transfers from nursing home to hospital. SETTING: The 120-bed nursing home care unit (NHCU) and the geographically separate 434-bed acute care facility (hospital) of the Portland Veterans' Affairs Medical Center (PVAMC). PATIENTS: Veterans hospitalized in the acute care division of NHCU. RESULTS: Following the introduction of MRSA into the NHCU in December 1987, it quickly disseminated. Two to 32 newly colonized or infected patients were recognized in each quarter of the study period. Facility-wide prevalence surveys on two occasions disclosed MRSA colonization rates of 34% and 10%. During the study period, 15 to 54 (mean: 37.6) patients were transferred each quarter from the NHCU to the hospital of the PVAMC. The number of MRSA cases transferred ranged from 0 to 16 per quarter (mean: 5.4). During the same period, the total number of MRSA cases in the hospital increased, rising from 7 cases in 1987 to 16 in 1988, 48 in 1989, 34 in 1990, and 35 in 1991. The percentage of hospital MRSA cases accounted for by NHCU transfers was 0% in 1988, 38% in 1989, 12% in 1990, and 11% in 1991. CONCLUSIONS: Despite the steady flow of patients between the NHCU and the hospital, the MRSA outbreak in the NHCU was associated with only a modest increase in the MRSA caseload at the affiliated hospital.

Infections caused by Staphylococcus aureus in a Veterans' Affairs nursing home care unit: a 5-year experience.

OBJECTIVES: To describe the frequency and patterns of infection caused by methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S aureus (MRSA) infections in a single nursing home population and to determine the effect of MRSA's entry into the facility on subsequent experience with both MSSA and MRSA infections. DESIGN: Observational and descriptive. Surveillance data on nursing home-acquired infections were reviewed to identify all patients with MSSA and MRSA infections occurring during the 5-year period from 1987 to 1991. The medical records of these patients were reviewed retrospectively to collect additional information about the patients and their infections. SETTING AND PATIENTS: A 120-bed Veterans' Affairs nursing home care unit (NHCU) whose residents predominantly were elderly men with severe underlying diseases and functional impairments. RESULTS: During the 5-year study period, 40 MSSA and 28 MRSA infections were acquired by NHCU residents. Twelve to 19 S aureus infections occurred each year. S aureus accounted for 13% to 17% of all NHCU-acquired infections during the years of study, occurring with a frequency of 0.29 to 0.47 infections per 1,000 resident-care days. MRSA infections, first detected in 1988, accounted for an increasing percentage of S aureus infections in subsequent years, but this increase had little effect on the facility's overall infection rates, the composite S aureus infection rates, or the types of infections observed. MSSA and MRSA infections acquired in the NHCU were comparable. Both affected patients with severe underlying diseases and functional impairments. Pneumonia, urinary tract infections, skin and soft tissue infections, and conjunctivitis were the types of infections observed most frequently, accounting for 28%, 25%, 22%, and 15% of all S aureus infections, respectively. Four bacteremic infections occurred in the MSSA group, and five in the MRSA group (P = .47). Four of the MSSA and three of the MRSA infections resulted in death (P = 1.0). Nine of the MSSA and 12 of the MRSA infections resulted in the patient's transfer to the associated acute care hospital for additional care (P = .13). CONCLUSIONS: In the NHCU setting, MSSA and MRSA infections were similar in terms of the types of residents affected, the sites involved, and the frequency of adverse outcomes. The entry of MRSA into the facility appeared to have no effect on the subsequent experience with NHCU-acquired infections caused by S aureus.

Antimicrobial therapy for methicillin-resistant Staphylococcus aureus colonization in residents and staff of a Veterans Affairs nursing home care unit.

OBJECTIVE: To evaluate the effect of antimicrobial therapy on patients and staff colonized with methicillin-resistant Staphylococcus aureus (MRSA) in a skilled nursing facility and to assess the role of the environment as a potential reservoir for MRSA in the nursing home setting. DESIGN: As part of a comprehensive program to control an MRSA outbreak in a nursing home, patients and staff colonized with MRSA received 1 of 3 antimicrobial decolonization regimens depending upon the site and extent of colonization. Followup cultures were performed during therapy and on days 2, 7, 14, and 30 following the completion of therapy. Cultures of the patients' inanimate environment (pajamas, sheet, and floor) were obtained during and after therapy. Antimicrobial susceptibility tests were performed on 54 MRSA isolates obtained before and 44 MRSA isolates recovered after therapy. SETTING: A 120-bed Veterans Affairs nursing home care unit. PARTICIPANTS: Thirty-six patients and 7 staff nurses colonized with MRSA at 1 or more sites. INTERVENTION: Decolonization therapy with rifampin, trimethoprim-sulfamethoxazole, and clindamycin used alone or in various combinations for 5 or 10 days in conjunction with other infection control measures employed to combat the MRSA outbreak. RESULTS: Twenty (56%) of the 36 NHCU patients were either persistently colonized or became recolonized with MRSA during the 30-day followup period. Positive cultures on day 3 during therapy frequently identified patients who subsequently exhibited persistent or recurrent colonization. Before therapy, 92% of MRSA isolates were susceptible to rifampin, whereas only 43% of the isolates obtained after therapy were susceptible. Sixteen (80%) of 20 patients with persistent or recurrent colonization had rifampin-resistant strains of MRSA isolated after therapy. Twenty-three (18%) of 125 environmental cultures obtained during and after therapy from patients who exhibited persistent or recurrent colonization were positive for MRSA, in contrast to 9 (8%) of 107 from patients who were successfully decolonized. CONCLUSIONS: The decolonization component of the outbreak control program was judged to be ineffective and potentially hazardous because colonization persisted or recurred in more than half of the patients, and substantial antimicrobial resistance was noted in MRSA stains isolated after therapy. Resistance, especially to rifampin, and possibly re-acquisition of MRSA from other human or environmental sources were 2 factors that appeared to impede the decolonization effort.

Methicillin-resistant Staphylococcus aureus in extended-care facilities: experiences in a Veterans' Affairs nursing home and a review of the literature.

OBJECTIVES: To delineate the spread of methicillin-resistant Staphylococcus aureus (MRSA) in a nursing home care unit (NHCU), determine its consequences, and discuss this experience in the context of reports from other nursing homes. DESIGN: Observational and descriptive; routine and special surveillance for MRSA, including a facility-wide prevalence survey; characterization of MRSA isolates by disk diffusion and agar dilution susceptibility studies and restriction enzyme analysis of plasmid (REAP) DNA. SETTING AND PATIENTS: A 120-bed skilled nursing facility that is an integral part of the Veterans' Affairs Medical Center (VAMC), Portland, Oregon. The patients are predominantly elderly men with severe underlying diseases and functional impairments. RESULTS: An asymptomatic carrier brought MRSA into the NHCU in December 1987. During the next 15 months, 24 additional MRSA cases were detected. A prevalence survey conducted in March 1989 indicated that 39 (34%) of the 114 patients and 8 (7%) of the 117 employees were colonized or infected with MRSA. All strains were resistant to ciprofloxacin. REAP DNA indicated that 37 of 41 strains recovered in the March survey had identical patterns. Although 16 episodes of MRSA infection occurred in NHCU residents during 1988 through 1989, the outbreak had little effect on overall patterns of infectious morbidity and mortality in the facility. The outbreak, however, did result in an increased MRSA caseload at the medical center's acute-care division. CONCLUSIONS: During the last three years, MRSA colonization and infection have become common in the NHCU at the Portland VAMC; this experience parallels that reported by several nursing homes in other parts of the country.

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.

Vancomycin in Oregon: who's using it and why.

OBJECTIVE: To determine the proportion of vancomycin orders that are appropriate according to national guidelines and to identify targets for educational messages. DESIGN: Population-based study of vancomycin use in Oregon during a 3-week period. Survey of pharmacists, prospective flagging of vancomycin orders, and data abstraction from patient charts using standardized forms. SETTING: Nonpsychiatric hospitals in Oregon. RESULTS: Four (6%) of the 66 Oregon hospitals had pharmacy restrictions on initial vancomycin orders. Sixty-four (97%) of the hospitals participated in the study of indications for use; 293 vancomycin orders were reported; 3.8 courses were initiated per 1,000 patient-days. Indications for use were determined for 266 (91%); of these, 159 (60%) were deemed appropriate. Of uses for prophylaxis, empirical treatment of suspected gram-positive infection, and treatment of documented gram-positive infection, 57%, 56%, and 65%, respectively, were appropriate. Of hospitals with <250, 251-475, and >475 licensed beds, 65%, 58%, and 57% of vancomycin orders were appropriate. No single medical specialty accounted for >16% of inappropriate vancomycin use. CONCLUSIONS: Vancomycin was used inappropriately by physicians of many different specialties, in hospitals of all sizes, and in sundry clinical situations. The problem of inappropriate vancomycin use does not lend itself to solution by educational strategies targeted at specific subgroups; restrictions by hospital pharmacies may be required.

Incidence and impact of infection in a nursing home care unit.

In this study we examined the frequency of infection and its consequences in a Veterans Administration medical center nursing home care unit during its first 9 months of operation. A total of 231 patients were enrolled and were followed up for an average stay of 115 days. Sixty-nine infections occurred in 50 patients and yielded a period prevalence rate of 22% and an infection incidence rate of 2.6 infections per 1000 days of patient care. Symptomatic urinary tract infections, pneumonia, and skin and soft tissue infections accounted for 41%, 32%, and 17% of the infections, respectively. Staphylococci, streptococci, and aerobic gram-negative bacilli were the most common bacterial isolates. Thirty-four episodes of infection (49%) required administration of parenteral antibiotics in the nursing home care unit, and 21 episodes (30%) necessitated transfer to the acute care hospital for management. Infection caused one death and contributed to the death of 4 of the 55 other patients who died during the study period.

Renal amyloidosis with nephrotic syndrome in two patients with schistosomiasis mansoni and chronic salmonellosis.

This report describes two Egyptian patients who presented with the nephrotic syndrome and concurrent infections with Schistosoma mansoni and Salmonella paratyphi A. Unlike similar cases previously reported from this unit, these patients did not respond to antimicrobial and antischistosomal therapy, and their renal biopsies demonstrated amyloidosis. These two case reports and several experimental observations suggest that chronic schistosomiasis and salmonellosis may lead to secondary amyloidosis in susceptible individuals.

Vertebral osteomyelitis and native valve endocarditis caused by Staphylococcus warneri.

Coagulase-negative staphylococci almost invariably cause significant clinical infections in the setting of prosthetic devices or severely compromised host defenses. Hematogenous osteomyelitis and native valve endocarditis due to these pathogens in any setting is rare. We report a case of community-acquired vertebral osteomyelitis and native valve endocarditis due to Staphylococcus warneri in a patient with none of the usual risk factors.

Staphylococcus epidermidis arthritis following catheter-induced bacteremia in a neutropenic patient.

Sepsis due to methicillin-resistant Staphylococcus epidermidis occurred in a neutropenic man during management with a Hickman-Broviac catheter. Despite catheter removal and 10 days of i.v. cefazolin therapy, he developed septic arthritis 6 weeks later in a nonprosthetic hip joint. S. epidermidis was isolated from the joint and found to have plasmid and phage susceptibility patterns identical to the previous blood isolate. This case is the first to document a metastatic infection from catheter-associated S. epidermidis bacteremia. It suggests that cephalosporins may not be optimal in such infections despite in vitro sensitivity. Vancomycin appears to be the drug of choice for S. epidermidis bacteremia in the neutropenic population.

Sensitivity of surveillance cultures for the detection of methicillin-resistant Staphylococcus aureus in a nursing-home-care unit.

This study compared the sensitivity of nasal culture alone versus multiple-site cultures and single versus duplicate sampling for the detection of methicillin-resistant Staphylococcus aureus (MRSA)-colonized individuals in a nursing-home population. Repeat culture of 68 specimens collected from 35 colonized subjects yielded identical results for 57 specimens, (84%), and 89% of the colonized residents (31 of 35) were identified by the first culture of multiple sites. A single nares culture detected 27 (77%) of 35 (first screen) and 29 (83%) of 35 (second screen) residents colonized with MRSA at any site. The most cost-effective screening would consist of a nasal culture only or combined with a gastrostomy tube site, if applicable. To identify all colonized individuals, however, it would be necessary to culture more than one specimen from multiple sites on each resident.

An unusual complication of cardiac transplantation--infected aortic pseudoaneurysm.

Infections after cardiac transplantation are a frequent cause of early morbidity and mortality. An unusual site for such a complication is at the aortic anastomotic suture line. We report a case of an infected aortic pseudoaneurysm, seen as recurrent septicemia, during the first 6 months after cardiac transplantation.

Intracarotid infusions of protamine sulfate disrupt the blood-brain barrier of rabbits.

This study examined the effect of intracarotid infusions of protamine sulfate on the blood-brain barrier of the rabbit. Evans blue, which binds tightly to serum albumin, served as the marker for blood-brain barrier disruption. Brains from 12 of 14 rabbits receiving 30-50 mg of protamine sulfate in an intracarotid infusion over 3 min demonstrated intense Evans blue-albumin staining in the distribution of the infused internal carotid artery. In contrast, brains from 5 animals receiving 0.9% saline and from 5 animals receiving 50 mg of protamine sulfate by the intravenous route showed no evidence of blood-brain barrier disruption. Premixing protamine sulfate with heparin prior to intracarotid administration greatly reduced or abolished Evans blue staining of the brain as did delayed administration of the marker dye. Thus, the interaction of the positively charged protamine molecule with the vascular endothelium of cerebral capillaries transiently alters the permeability of the blood-brain barrier in the rabbit.

Hematologic manifestations of bacterial and fungal infections.

Bacterial and fungal infections have a varied and often profound effect on the cellular elements of the blood and the hemostatic system. These infections may increase or decrease numbers of circulating erythrocytes, leukocytes, and platelets or may induce qualitative changes in these elements, some of which affect their function. Bacterial and fungal infections may also produce thrombosis or hemorrhage. They exert these effects through mechanisms that involve specific microbial virulence factors or host defenses mobilized against the infectious agents. This article focuses on the diverse hematologic manifestations of bacterial and fungal infections in the context of these mechanistic considerations.

Chronic cutaneous infection caused by Mycobacterium intracellulare.

A 53-year-old woman had multiple ulcerative skin lesions caused by Mycobacterium intracellulare. The original lesions had appeared on her face and upper part of her chest at least 11 years earlier and had progressed slowly to involve large areas of her head and trunk. This unusual skin infection demonstrates chronicity and destructiveness.

Antimicrobial activity, pharmacokinetics, adverse reactions, and therapeutic indications of cefoperazone.

Cefoperazone is a parenteral cephalosporin antibiotic that is pending approval by the U. S. Food and Drug Administration. Compared to most other cephalosporins cefoperazone has a greatly expanded spectrum of bactericidal activity that encompasses most aerobic gram-positive bacteria except enterococci, most aerobic gram-negative bacteria, including a majority of Pseudomonas aeruginosa strains, and a number of pathogenic anaerobic bacteria. Its long serum half-life, approximately two hours, permits a twelve hourly dosing schedule. No dosage modification is required in patients with renal insufficiency, and only minor modification is needed in patients with hepatic insufficiency or biliary obstruction. Clinical trials have established cefoperazone's efficacy in lower respiratory tract infections, urinary tract infections, and a variety of other bacterial infections. Adverse reactions have been infrequent, and few serious reactions have been identified. Cefoperazone is a promising new agent for the treatment of gram-negative bacillary and polymicrobial infections, especially in settings that require empiric therapy.

Antimicrobial agents and the central nervous system.

There is an ever-expanding number of antimicrobial agents available for the clinician to use to combat infections. We review the majority of such agents that are currently available relative to their theoretical or proven efficacy in the treatment of CNS infections. Due to the unique ability of the CNS to exclude many agents delivered via the blood stream, easily administered and efficacious therapy remains a problem. Based on the pharmacokinetics of anti-infective drugs and their antimicrobial spectrum, at present a penicillin derivative or chloramphenicol should be used whenever possible because parenteral therapy will usually achieve the desired results. In many neurosurgery-associated infections, intrathecal or intraventricular antibiotics may be required to supplement parenteral treatment and/or surgical intervention. Some of the more promising agents (such as rifampin, trimethoprim-sulfamethoxazole, and metronidazole) await further clinical trials to establish their place in the therapeutic armamentarium. Careful, randomized, prospective studies of prophylactic antibiotics must be performed in the neurosurgical setting. A group of tables are included that summarize the expected spinal fluid levels, the sensitivities of organisms commonly causing neurosurgical infections, doses of drugs given intrathecally or intraventricularly, and recommended regimens for certain infections.

Toxic shock syndrome. Are you recognizing its changing presentations?

Nonmenstrual cases of toxic shock syndrome now occur at least as often as the classic menstrual cases. The syndrome has been reported in every conceivable clinical setting involving colonization or infection with Staphylococcus aureus and as a complication of surgical procedures, traumatic injuries, and local infections. Unusual clinical manifestations have been observed in patients with AIDS. Cases of toxic shock syndrome also have been linked to infection with toxin-producing strains of coagulase-negative staphylococci and group A streptococci. Knowledge of the expanding spectrum of toxic shock syndrome and early consideration of the disease in patients with fever, hypotension, rash, and/or multisystem disease are essential for timely diagnosis and optimum management.