RISE-resistant tuberculous meningitis in AIDS patient.
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
S M Opal
Publications and source records attributed to S M Opal.
Spread of methicillin-resistant Staphylococcus aureus in a hospital after exposure to a health care worker with chronic sinusitis.
A dramatic increase in the incidence of methicillin-resistant Staphylococcus aureus at a teaching hospital was documented to be due to three factors: a hospital-wide outbreak of 32 cases caused by an epidemic strain, an increase in the number of nosocomial cases caused by several other strains, and an increase in the number of patients admitted carrying strains acquired at other institutions. Case patients with the epidemic strain were significantly more likely than control patients to have had previous exposure to a respiratory therapist (P = .005) who had chronic sinusitis due to the epidemic strain. The plasmid DNA of isolates from the implicated respiratory therapist and affected patients yielded the same patterns on restriction endonuclease digestion. Implementation of general control measures and eradication of the respiratory therapist's sinusitis and nasal carriage terminated the epidemic. Establishing the importance of the infected health care worker by epidemiological methods led to control of the outbreak without the institution of wide-scale culture of specimens from personnel and the environment or other expensive and labor-intensive measures.
Aged↗
The efficacy of combination immunotherapy in experimental Pseudomonas sepsis.
Immunotherapy has been shown to be an effective adjuvant in the management of septic shock. A neutropenic rat model of septic shock induced by infection with Pseudomonas aeruginosa 12.4.4 (Fisher immunotype 6) was used to determine the relative efficacy of single, double, and triple combination immunotherapy. A Pseudomonas O serotype-specific, opsonophagocytic monoclonal antibody (MAb), polyclonal J5 antiserum, and a MAb directed against tumor necrosis factor-alpha (TNF) were studied as single therapy and in combination. The combination of all three immunotherapeutic agents resulted in a 77% survival rate (33/43 animals). This level of protection was superior to that achieved with any combination of two antibody treatments (50%-60% survival; P = .029) or single antibody therapy (25%-43% survival; P < .001) or compared with a control group (0/25 survivors; P < .0001). Immunotherapy directed against multiple steps of the septic process is more active than single or double antibody regimens and may offer an improved approach to the adjunctive treatment of septic shock.
Animals↗
Efficacy of anti-endotoxin monoclonal antibody E5 alone or in combination with ciprofloxacin in neutropenic rats with Pseudomonas sepsis.
Pathogen-free rats were rendered neutropenic, given oral feedings of Pseudomonas aeruginosa 12.4.4, then monitored for fever. At the onset of fever, rats were given intravenous treatment with either anti-endotoxin monoclonal antibody (MAb) E5 or control MAb B55. Survival was significantly greater in E5- than in B55-treated animals (P < .01). Serum levels of both lipopolysaccharide and tumor necrosis factor-alpha were significantly reduced in E5- versus B55-treated rats 24 h after treatment (P < .01 and < .05, respectively). Rats were also treated with E5 or B55 in combination with a suboptimal dose of ciprofloxacin at fever onset and again 24 h later. Survival was significantly greater in ciprofloxacin-treated animals given E5 than in animals given B55 (P < .005). Posttreatment endotoxin levels were decreased in animals receiving E5 in combination with ciprofloxacin (P < .001) compared with B55-treated animals. These results indicate that therapy with anti-endotoxin MAb E5 alone or in combination with antimicrobial therapy improves survival in this bacteremic infection model of Pseudomonas sepsis.
Animals↗
Influence of an anti-tumor necrosis factor monoclonal antibody on cytokine levels in patients with sepsis. The CB0006 Sepsis Syndrome Study Group.
OBJECTIVES: To determine the safety, pharmacokinetics, and activity of an anti-tumor necrosis factor (TNF)-alpha monoclonal antibody in severe sepsis. DESIGN: Open-label, prospective, phase II multicenter trial with escalating doses of a murine monoclonal antibody (CB0006). SETTING: Twelve academic medical center intensive care units in the United States and Europe. PATIENTS: Eighty patients with severe sepsis or septic shock who received standard supportive care and antimicrobial therapy in addition to the anti-TNF antibody. INTERVENTIONS: Patients were treated intravenously with one of four dosing regimens with CB0006: 0.1 mg/kg, 1.0 mg/kg, 10 mg/kg or two doses of 1 mg/kg 24 hrs apart. MEASUREMENTS AND MAIN RESULTS: The murine monoclonal anti-TNF antibody was well tolerated despite the development of anti-murine antibodies in 98% of patients. No survival benefit was found for the total study population, but patients with increased circulating TNF concentrations at study entry appeared to benefit by the high dose anti-TNF antibody treatment. Increased interleukin (IL)-6 levels predicted a fatal outcome (p = .003), but TNF levels were not found to be a prognostic indicator. TNF levels were higher (206.7 +/- 60.7 vs. 85.9 +/- 26.1 pg/mL; p < .001) and outcome was poor (41% vs. 71% survival; p = .007) in patients who were in shock at study entry when compared with septic patients not in shock. CONCLUSIONS: The murine anti-TNF-alpha monoclonal antibody CB0006 has proven to be safe in this clinical trial and may prove to be useful in septic patients with increased circulating TNF concentrations. Further studies are needed to determine efficacy and the ultimate clinical utility of this immunotherapeutic agent in sepsis.
Antibodies, Monoclonal↗
Choice of bacteria in animal models of sepsis.
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Animals↗
The impact of converting to a biphasic blood-culture system on the overall cost and the incidence of pseudobacteremia.
After converting from a conventional broth (CB) system to a biphasic (BP) agar-slide blood-culture system (Septi-Chek), our laboratory noted an increase in positive blood cultures in general, and in coagulase-negative staphylococci (CNS) in particular. To investigate these findings, we compared all blood cultures collected over a 21-month period using CB and then BP systems, totaling 28,199 blood cultures. The frequency of positive blood cultures increased from 9.2% to 12.7% (p less than 0.0001), whereas CNS isolation increased from 2.6% to 5.2% (p less than 0.0001). There was no significant change in the incidence of true primary or secondary bacteremia due to CNS (p = 0.9). The isolation of other pathogens, including Staphylococcus aureus, Candida albicans, Bacteroides species, and Gram-negative bacilli increased from 6.5% to 7.1% (p less than 0.05). We estimated the cost of processing 28,000 blood cultures by both CB and BP systems, using positivity rates of 9.2% and 12.7%, respectively, and standards provided by the College of American Pathologists (CAP, 1991) for workload hours of technologist time. We calculated a higher overall cost for the BP system. However, the use of this system eliminated the use of needles and syringes for subculture of bottles showing no growth, thus decreasing the risk of technologist exposure to body fluids. Despite the increased cost and more frequent occurrence of pseudobacteremia, the enhanced sensitivity and increased safety of the BP system justified its use in the prompt identification of patients with true bacteremia.
Bacteremia↗
Emergence and nosocomial transmission of ampicillin-resistant enterococci.
Between 1986 and 1988, the incidence of ampicillin-resistant enterococci increased sevenfold at a university-affiliated hospital. Forty-three patients acquired nosocomial infections with ampicillin-resistant enterococci, most of which were also resistant to mezlocillin, piperacillin, and imipenem. An analysis of plasmid and chromosomal DNAs of isolates revealed that the increase was due to an epidemic of 19 nosocomial infections that yielded closely related strains of Enterococcus faecium and to a significant increase in the incidence of nonepidemic, largely unrelated strains of ampicillin-resistant enterococci. The nonepidemic strains were identified as E. faecium, E. raffinosus, E. durans, and E. gallinarum. A logistic regression analysis revealed that patients with nonepidemic resistant strains were 16 times more likely than controls to have received preceding therapy with imipenem. In our institution, the increase in the incidence of ampicillin-resistant enterococci appears to be due to the selection of various strains of resistant enterococci by the use of imipenem and to the nosocomial transmission of E. faecium and E. raffinosus.
Adult↗
Modulation of blood-brain barrier permeability by tumor necrosis factor and antibody to tumor necrosis factor in the rat.
In an attempt to understand the role of TNF in the central nervous system (CNS) pathophysiologic events associated with bacterial meningitis, we examined the effect of intravenous vs. intracisternal administration of TNF alpha on penetration of circulating 125I-labeled albumin into cerebrospinal fluid (CSF) and CSF white blood cell (WBC) counts in rats. Intracisternal administration of tumor necrosis factor alpha (TNF-alpha) resulted in dose- and time-dependent alterations of the CSF penetration and CSF WBCs, while intravenous administration of TNF-alpha did not induce any changes. These changes by intracisternal TNF were abolished by heat treatment of TNF or coadministration of MAb to TNF-alpha. Mab to TNF-alpha also significantly reduced the CSF penetration of circulating albumin in experimental hematogenous Haemophilus influenzae type b meningitis in infant rats but this salutary effect required both intravenous and intracisternal administration. However, MAb to TNF-alpha failed to affect CSF pleocytosis in experimental hematogenous meningitis. These findings suggest that some of CNS pathophysiologic changes in bacterial meningitis may be a result of the local production of TNF but other host inflammatory responses may also participate in CNS inflammation in hematogenous bacterial meningitis.
Animals↗
Failure of ciprofloxacin to eradicate convalescent fecal excretion after acute salmonellosis: experience during an outbreak in health care workers.
OBJECTIVE: To determine the efficacy of ciprofloxacin therapy in eradicating convalescent fecal excretion of salmonellae after acute salmonellosis. DESIGN: Randomized, placebo-controlled, double-blind trial of ciprofloxacin, with prospective follow-up of nonparticipants. SETTING: An acute care community hospital experiencing an outbreak of salmonellosis. PATIENTS: Twenty-eight health care workers developed acute infection with Salmonella java; 15 participated in a placebo-controlled trial of ciprofloxacin, beginning on day 9 after infection. INTERVENTIONS: Eight patients were randomly assigned to receive ciprofloxacin, 750 mg, and 7 patients to receive placebo; both were administered orally twice daily for 14 days. Nonparticipants who received therapy were placed on the same ciprofloxacin regimen. MEASUREMENTS AND MAIN RESULTS: Study participants had follow-up stool cultures every 3 days initially and then weekly for 3 weeks; nonparticipants were followed until three consecutive cultures were negative. All eight ciprofloxacin recipients showed eradication of S. java from stool cultures within 7 days of beginning therapy (compared with 1 of 7 placebo recipients), and their stool cultures remained negative up to 14 days after discontinuing therapy (P less than 0.01). However, 4 of 8 relapsed; their stool cultures became positive between 14 and 21 days after therapy. In addition, 3 of 3 hospitalized patients treated with ciprofloxacin who did not participate in the controlled trial also relapsed. Thus, the total relapse rate was 7 of 11 (64%; 95% CI, 31% to 89%). In 4 of these 7 patients, relapse was associated with a longer duration of fecal excretion of salmonellae than that of the placebo group. Relapse could not be explained on the basis of noncompliance, development of resistance, or presence of biliary disease. CONCLUSIONS: Despite its excellent antimicrobial activity against salmonellae and its favorable pharmacokinetic profile, ciprofloxacin at a dosage of 750 mg orally twice daily had an unacceptably high failure rate in patients with acute salmonellosis and may have prolonged fecal excretion of salmonellae. The late occurrence of relapses indicates the need to obtain stool cultures up to 21 days after therapy to document fecal eradication in acute salmonellosis.
Acute Disease↗
Malaria in travelers in Rhode Island: a review of 26 cases.
PURPOSE: We reviewed our experience with malaria in two community hospitals in Rhode Island from 1986 to 1990. RESULTS: Twenty-six patients with malaria were identified. Fifteen patients were immigrants who had acquired malaria while visiting their country of origin, particularly West Africa. Fever was present in 67% of cases and gastrointestinal complaints were prominent in 26%. Individuals with a past history of malaria could accurately distinguish current malarial infections from other febrile illnesses. Two patients developed cerebral malaria. Plasmodium falciparum was identified in 77% of the cases. CONCLUSIONS: Malaria is an important diagnosis that United States physicians must consider in the medical evaluation of returning travelers. A significant increase in the number of cases of P. falciparum acquired in East Africa has been reported in recent years. P. falciparum infection must be rapidly diagnosed and treated since delays may result in complications of malaria that may lead to death. Mefloquine is currently recommended by the Centers for Disease Control for prevention of malaria in travelers visiting countries endemic for chloroquine-resistant malaria. This change may alter the epidemiology of malaria in the United States in the future.
Adolescent↗
Efficacy of antilipopolysaccharide and anti-tumor necrosis factor monoclonal antibodies in a neutropenic rat model of Pseudomonas sepsis.
Monoclonal antibodies (MAb) directed against bacterial lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF) provide partial protection in experimental models of septic shock. To determine if additional benefit accrues from a combination of anti-TNF and anti-LPS MAb in the treatment of septic shock, a neutropenic rat model was developed to study active infection with Pseudomonas aeruginosa 12.4.4. Animals were treated intravenously with an irrelevant MAb (group 1); anti-TNF MAb (group 2); MAb directed against P. aeruginosa 12.4.4 LPS (group 3); or a combination of anti-TNF and anti-LPS MAb (group 4). None of the control animals in group 1 survived the 7-d period of neutropenia (0/16). In contrast, the survival rate was 44% in group 2 (P less than 0.02); 37% in group 3 (P less than 0.05); and 75% in group 4 (P less than 0.0002). The combination of monoclonal antibodies provided greater protection than either MAb given alone (P less than 0.05). Serum TNF levels during infection were significantly greater in groups 1 and 3 (20.1 +/- 3.3 U, mean +/- SE) than in groups 2 and 4 (0.9 +/- 0.8 U, P less than 0.0001). These results indicate that a combination of monoclonal antibodies to LPS and TNF have additive benefit in experimental Pseudomonas aeruginosa sepsis. This immunotherapeutic approach may be of potential utility in the management of serious, gram-negative bacterial infection in neutropenic patients.
Animals↗
Frequent acquisition of multiple strains of methicillin-resistant Staphylococcus aureus by healthcare workers in an endemic hospital environment.
Methicillin-resistant Staphylococcus aureus (MRSA) has been an endemic nosocomial pathogen at the VA medical center (VAMC) in Providence, Rhode Island since 1981. From 1985 to 1987, more than 30% of all unique S aureus isolates were methicillin resistant. To evaluate the frequency of acquisition of MRSA isolates by healthcare workers, we compared the antimicrobial susceptibility patterns, multilocus enzyme genotypes and plasmid profiles of isolates recovered from nasal and hand cultures from VAMC nurses and house staff on rotation at the VAMC with those of clinical isolates from patients at the VAMC and four other affiliated hospitals. Fifty-six percent of ward nurses cultured (n = 112) were colonized with S aureus, of which 65% was methicillin resistant. Six isolates of MRSA were identified on the initial culturing of house staff (n = 65); 16 MRSA isolates were recovered at the end of a four-week rotation (p less than .02). Phenotypic and genotypic analyses demonstrated that numerous distinct MRSA strains were recovered in the study period. The incidence of MRSA among clinical isolates at the VAMC and affiliated institutions was remarkably constant throughout the three-year study period. Moreover, despite regularly sharing resident physicians, interns and medical students, MRSA isolates were commonly recovered at the other university-affiliated hospitals. Our study failed to reveal evidence of significant interhospital transmission of MRSA isolates by healthcare workers. While healthcare workers may contribute to the dissemination of MRSA within institutions, they appear to be less important in spreading MRSA between institutions.
DNA, Bacterial↗
A common-source outbreak of Staphylococcus epidermidis infections among patients undergoing cardiac surgery.
A single strain of Staphylococcus epidermidis caused an outbreak of postoperative wound infections and endocarditis during a 6-month period. Infections caused by the epidemic strain developed more frequently in valve surgery patients than in those undergoing coronary artery bypass graft surgery (P = .03) and occurred only in patients operated on by surgeon A. None of 17 members of the cardiac surgery team carried the epidemic strain in their anterior nares, axillae, or inguinal folds. Hand cultures were performed on 8 surgical personnel, and only surgeon A carried the epidemic strain on his hands. Isolates from cardiac surgery patients, bypass pump blood cultures, and the hands of the implicated surgeon all had identical antimicrobial susceptibility patterns, plasmid profiles, and EcoRI restriction endonuclease digest patterns. In the 24 months after control measures were implemented, no infections caused by the epidemic strain occurred among open heart surgery patients. The findings suggest that the common-source outbreak of infections among cardiac surgery patients was due to carriage of a strain S. epidermidis on the hands of a cardiac surgeon.
Adult↗
Aerobactin and alpha-hemolysin as virulence determinants in Escherichia coli isolated from human blood, urine, and stool.
Because iron acquisition is essential to the survival of invasive strains of Escherichia coli, the frequency of two potential iron acquisition systems, aerobactin and hemolysin production, were compared in E. coli isolated from human blood (n = 95), urine (n = 100), and stool (n = 50). By phenotypic and genotypic methods, the prevalence of hemolysin production was 22% in bacteremic, 38% in urinary, and 22% in fecal isolates of E. coli. Aerobactin production was detected in 76% of blood and in 73% of urinary isolates but in only 52% of fecal isolates (P less than .01). A reciprocal relationship was found in blood isolates between aerobactin and hemolysin; the majority of blood isolates (55%) that lacked aerobactin were hemolytic, whereas only 14% of blood isolates that expressed aerobactin were hemolytic (P less than .0001). Aerobactin may be the principal mechanism of iron acquisition in extraintestinal isolates of E. coli, and hemolysin may serve as an alternative mechanism in the absence of aerobactin genes.
Bacterial Proteins↗
Efficacy of a monoclonal antibody directed against tumor necrosis factor in protecting neutropenic rats from lethal infection with Pseudomonas aeruginosa.
A monoclonal antibody directed against murine tumor necrosis factor-alpha (TNF) was studied in a neutropenic rat model to determine its efficacy in protecting animals from lethal infection with Pseudomonas aeruginosa. Anti-TNF monoclonal antibody at a dose of 20 mg/kg given intravenously at 0 and 120 h resulted in a 53% survival rate (8/15) compared with no survival in control animals (0/15) (P less than .005). The combination of anti-TNF monoclonal antibody and oral ciprofloxacin at a suboptimal dose of 2.5 mg/kg/day resulted in a 100% survival rate in neutropenic animals (16/16), while ciprofloxacin alone produced only a 67% survival rate (10/15) during the 7-day period of neutropenia (P less than .05). Thus anti-TNF monoclonal antibody alone or in addition to antimicrobial agents improved survival in neutropenic animals after infection with P. aeruginosa.
Agranulocytosis↗
Recent advances in infectious diseases.
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Acquired Immunodeficiency Syndrome↗