Vancomycin-resistant enterococcal bacteremia: natural history and attributable mortality.

Previous studies have shown that bacteremia due to vancomycin-resistant Enterococcus species (VRE) is associated with mortality of 17%-100%, but comorbid conditions may have confounded the estimates. We designed a historical cohort study to determine the mortality attributable to VRE bacteremia. Twenty-seven patients with VRE bacteremia were identified as cases. Within 7 days of the onset of bacteremia, severe sepsis developed in 12 patients (44%) and septic shock developed in 10 (37%). Case patients were closely matched to control patients without VRE bacteremia (1:1) by time of hospitalization, duration of exposure, underlying disease, age, gender, and surgical procedure. The mortality was 67% among cases and 30% among matched controls (P = 0.1). Thus, the mortality attributable to VRE bacteremia was 37% (95% confidence interval [CI], 10%-64%) and the risk ratio for death was 2.3 [CI, 1.2-4.1). We conclude that VRE bacteremia is associated with high rates of severe sepsis and septic shock. The attributable mortality approaches 40%, and patients who have VRE bacteremia are twice as likely to die than closely matched controls.

Clinically unsuspected epiglottitis detected by indium-111-white blood cell scintigraphy.

A 62-yr-old woman with a history of mental retardation, paranoid psychosis and agitated depression presented with deterioration in her baseline mental status and fever. No obvious source of fever was found on clinical exam or on initial laboratory studies. An 111In-white blood cell (111In-WBC) study was performed 1 wk after hospital admission, which revealed increased uptake in the anterior neck and oral cavity. Subsequent laryngoscopy revealed a red, swollen epiglottis compatible with epiglottitis. While not advocating 111In-WBC scintigraphy as part of the workup of epiglottitis, this case is presented to emphasize the possible milder presentation of epiglottitis in adults compared to children.

Late graft failure due to dual bone marrow infection with variants A and B of human herpesvirus-6.

Hematopoietic effects of human Herpesvirus-6 (HHV-6) infection following bone marrow transplantation (BMT) include delayed engraftment and early myelosuppression. Variant A has not been isolated after BMT. A case of graft failure is reported following an HLA-identical BMT for chronic myelogenous leukemia (CML) in chronic phase. Evaluation of bone marrow during the period of graft failure revealed variants A and B of HHV-6 by culture, immunofluorescence, polymerase chain reaction (PCR), and immunohistochemistry. Evidence for other cases of graft failure, including cytomegalovirus (CMV), could not be found. A hypothesis is proposed that late graft failure in this case was due to variant A of HHV-6.

Vancomycin-resistant Enterococcus faecium bacteremia: risk factors for infection.

We describe an outbreak of vancomycin-resistant Enterococcus faecium (vanA phenotype) bacteremia on the oncology ward of a tertiary care community hospital. In 10 of the 11 cases the patients had leukemia and were neutropenic (median duration of neutropenia, 21 days) at the time of bacteremia. On average, patients received six antibiotic agents for a total of 61 agent-days prior to development of vancomycin-resistant E. faecium bacteremia. The mortality rate was 73%. Molecular typing of 22 isolates revealed that the majority (83%) represented a common strain, indicating nosocomial spread. When the 11 cases were compared to 22 matched control patients, gastrointestinal colonization with vancomycin-resistant E. faecium (odds ratio [denominator, 0] infinity, P = .005) and the use of antimicrobial agents with significant activity against anaerobes (metronidazole, clindamycin, and imipenem; odds ratio infinity, P = .02) were found to be risk factors for the development of vancomycin-resistant E. faecium bacteremia. Since no proven therapy for such infection exists, there is an urgent need to identify effective measures to prevent and control the development of vancomycin-resistant E. faecium bacteremia.

Long-term survival after allogeneic bone marrow transplantation complicated by trichosporosis.

We report a case of sepsis due to Trichosporon cutaneum in a 20-year-old patient with acute promyelocytic leukemia. Neutropenia with a hypocellular marrow persisted for 90 days after two courses of induction chemotherapy with mitoxantrone and ara-C. Amphotericin B, fluconazole, and granulocyte-macrophage colony-stimulating factors were administered. Neutropenia (ANC < 1,000/microL) resolved 14 days after HLA-identical bone marrow transplantation. The patient is in remission, with a performance status of 100%, more than 1 year after transplantation.

Some factors that influence dropping out from outpatient alcoholism treatment facilities.

Even though clients treated in an outpatient setting have been documented to have very high dropout rates, evidences of the factors that influence dropping out are fragmentary and are based on small-scale studies. In our attempt to distinguish such factors, outpatient and intensive outpatient alcoholism admissions for the State of New Jersey were analyzed. Our findings indicated that females, the young and the unskilled are at a higher risk of dropping out. We also documented that drinking status of patients, occupational status, health insurance coverage, educational status, living arrangement, duration of stay in treatment and the number of sessions of service were important factors that influenced the likelihood of dropping out. Controlling for the number of sessions revealed that the relationship between the odds of dropping out and duration in treatment was mixed. Primary drug abusers in our cohort had the highest likelihood of dropping out followed by the dually addicted. It is argued that dropping out is likely to be complicated by the inability of alcoholism treatment facilities to cope with multiple addiction problems.

Prospective observational study of Klebsiella bacteremia in 230 patients: outcome for antibiotic combinations versus monotherapy.

Combination antimicrobial agent therapy has been advocated for treatment of gram-negative bacteremia, including that caused by Klebsiella spp. We performed a prospective, observational, 10-hospital collaborative study to evaluate the efficacy of antibiotic combination therapy versus that of monotherapy for 230 consecutive patients with Klebsiella bacteremia. The species involved were K. pneumoniae (82%), K. oxytoca (15%), and K. ozaenae (0.4%). Of the bacteremias, 26% were polymicrobial in nature. A total of 53% of cases were nosocomial infections. The most common portals were the urinary tract (28%), biliary tract (12%), lung (10%), and abdomen (9%). Some 49 and 51% of the patients had received monotherapy and antibiotic combination therapy (beta-lactam plus aminoglycoside), respectively; 14-day mortalities in the two groups were 20 and 18%, respectively. However, for the subgroup of patients who experienced hypotension within 72 h prior to or on the day of the positive blood culture, those patients who received combination therapy experienced significantly lower mortality (24%) than did those who received monotherapy (50%). We conclude that monotherapy with an antibiotic that is active in vitro against Klebsiella (beta-lactam or aminoglycoside) is sufficient therapy for less severely ill patients (immunocompetent, urinary tract portal, mentally alert, normal vital signs). On the other hand, for severely ill patients who experience hypotension, antibiotic combination therapy with a beta-lactam and an aminoglycoside agent is preferred.

Chronic necrotizing pulmonary aspergillosis treated by endobronchial amphotericin B.

Chronic necrotizing pulmonary aspergillosis is an indolent, locally invasive form of Aspergillus infection. Treatment options are limited and controversial. Resection is often curative if the patient has sufficient ventilatory reserve. Even though intravenous amphotericin B is effective in a few patients, toxicity limits its use. Aerosolized amphotericin B has proven ineffective. Anecdotal reports of intracavitary and endobronchial antifungal therapy show limited success. Our patient had unresectable chronic necrotizing pulmonary aspergillosis treated successfully with intracavitary instillation of amphotericin B, delivered via the flexible fiberoptic bronchoscope.

Liver cirrhosis with and without mention of alcohol as cause of death.

Changes in the estimated proportion of liver cirrhosis deaths attributable to alcoholism in the United States from 1940 to 1980 are reviewed. The value of this proportion from 1940 in the original Jellinek Alcoholism Estimation Formula, through Formula modifications, to 1980 use are presented; the rationale for various changes in its value are discussed. Essex County, New Jersey, USA decedents in 1984, aged 25-years or older, whose underlying cause of death was specified alcoholic cirrhosis and those who died of cirrhosis without mention of alcohol are analyzed for differences in background and post-mortem characteristics. Some appreciable proportion of cirrhosis deaths without mention of alcohol is considered to be attributable to alcoholism. Background and post-mortem differences between persons whose underlying cause of death is certified as cirrhosis with and without mention of alcohol suggest some bases for the under-reporting of specified alcoholic cirrhosis mortality.

Occult pneumococcal bacteremia and empyema without preceding pulmonary parenchymal involvement.

We have presented a case of pneumococcal empyema without evidence of pulmonary parenchymal infection. We postulate that the pleural space was hematogenously seeded from an unexplained pneumococcemia. This manifestation of pneumococcal infection is unusual, particularly since the patient was receiving adequate antibiotic therapy before the radiologic or clinical appearance of the empyema. This emphasizes the need for diagnostic thoracentesis when the clinical situation changes, even after appropriate antimicrobial therapy is begun.

Opsonic requirements for phagocytosis of Legionella micdadei by polymorphonuclear leukocytes.

The roles of the classical and alternative pathways of complement activation and of antibody in the phagocytosis of Legionella micdadei by polymorphonuclear leukocytes were studied. Normal serum was treated with the appropriate chelators or with heat to inactivate the classical, alternate, or both pathways of complement activation. Normal and complement-depleted sera with or without antibody were employed as opsonins for L. micdadei in phagocytosis assays. There was no difference in the phagocytosis of L. micdadei promoted by normal serum and either C4-deficient serum or serum in which the classical pathway had been inactivated. Both normal and classical pathway-deficient sera promoted significantly greater phagocytosis than did sera in which the alternate pathway or both the alternate and classical pathways had been inactivated. Thus, polymorphonuclear leukocyte phagocytosis of L. micdadei in the absence of antibody required an intact alternate pathway. Specific antibody partially restored opsonization to sera deficient in the alternate or both complement pathways, but phagocytosis was still significantly less than that with the alternate pathway intact.

Metastatic bacterial endophthalmitis.

Metastatic bacterial endophthalmitis has been reported infrequently in the antibiotic era. We recently encountered five cases of metastatic bacterial endophthalmitis during an eight-month period. The diagnosis was made by blood culture in four of the cases and a positive vitreal aspirate in the fifth case. The organisms included: Staphylococcus aureus, Streptococcus pneumoniae, and groups G and B streptococci. Underlying diseases included endocarditis, lymphoma, and facial trauma. One patient had no identifiable source of infection. The diagnosis was delayed in two of the patients, despite early ophthalmologic consultation. The outcome was poor, four of the five patients lost all useful vision. Development of eye symptoms in the setting of gram-positive bacteremia should be suggestive of this entity. An aggressive diagnostic and therapeutic approach with intravitreal antibiotics might improve the outcome. Our observation of five cases during eight months in one hospital suggests that metastatic endophthalmitis may be more common than is generally appreciated.

Interaction of Legionella micdadei with human monocytes.

We have recently shown that Legionella micdadei is ingested, but not killed, by human neutrophils. Herein we investigate the role of human monocytes in defense against this organism. Serum and monocytes from normal donors having no detectable antibody to L. micdadei were used. Egg-passaged L. micdadei organisms multiplied inside these monocytes with a peak growth of 2 log units within 12 h. No growth occurred when monocytes were omitted or when sonicated monocytes were used. Electron microscopy 18 h after infection revealed these organisms to be intracellular in normal-appearing phagosomes. When the input multiplicity of L. micdadei was greater than 1 CFU per monocyte, no intracellular growth occurred. When egg-passaged Legionella pneumophila organisms were used, intracellular organisms were found in phagosomes studded with ribosomes at the same time period. Peak intracellular growth of L. pneumophilia occurred by 48 h. L. micdadei activated the complement system and was opsonized by C3. However the use of complement-depleted (heat-inactivated) serum as the opsonic source had no effect on the bacterium's ingestion or growth in the monocyte. Thus, L. micdadei multiples in human monocytes. This entry and growth is independent of antibody or complement. The intracellular locations of L. micdadei and L. pneumophila differ, suggesting different mechanisms for the survival of these two organisms in the monocyte.

Human polymorphonuclear leukocyte interaction with cyclosporine A.

The effects of cyclosporin A (cyA) on human polymorphonuclear leukocyte function, including phagocytosis, its associated metabolic burst, bacterial killing, and chemotaxis, were evaluated. Both Pseudomonas aeruginosa and Staphylococcus aureus were used as test particles. Polymorphonuclear leukocytes incubated in 10 and 50 micrograms of cyA per ml behaved normally with respect to phagocytosis and hexose monophosphate shunt activity at both high (10:1) and low (2:1) S. aureus/leukocyte ratios. With a small bacterial inoculum, killing of S. aureus was slightly impaired at early times only in the presence of 50 micrograms of cyA per ml. Phagocytosis and killing of P. aeruginosa with both large and small bacterial inocula were unaffected by cyA. Chemotaxis was within normal limits under all conditions. In addition, polymorphonuclear leukocytes from four renal transplant recipients receiving both cyA and prednisone demonstrated normal metabolic bursts and bacterial killing with both small and large inocula of S. aureus.

The contribution of human neutrophils and serum to host defense against Legionella micdadei.

The interaction of Legionella micdadei with human polymorphonuclear neutrophils (PMNs) and serum was investigated to determine their roles in host defense against this organism. Serum and PMNs from normal donors having no antibody to L micadei were used. PMNs phagocytized once-agar-passaged (74.6% +/- 6.5%) and twice-agar-passaged (87.3% +/- 1.0%) L micdadei less (P less than 0.05) than L micdadei passaged multiple times on agar (97.5% +/- 1.0%) or Staphylococcus aureus (98.3% +/- 0.5%). Under the same conditions, no phagocytosis of Legionella pneumophila occurred. Use of heat-inactivated serum abolished phagocytosis. PMN killing of once-agar-passaged (1.5% +/- 1.5%) and twice-agar-passaged (0) L micdadei was less (P less than 0.001) than that of L micdadei passaged multiple times on agar (88.6% +/- 4.0%) or S aureus (96.8% +/- 0.5%). L micdadei was not killed by fresh serum, although, in contrast to L pneumophila, it was opsonized by C3. Thus virulent L micdadei is phagocytized, but not killed, by human PMNs, with complement being the major opsonin.

Human neutrophil membrane topography: examination of distribution, movement, and regeneration of recognition sites using lectins as probes.

We have studied the pattern of membrane binding site redistribution, movement, and reappearance in polarized and nonpolarized human neutrophils using fluorescein and rhodamine-labeled lectins as probes. In suspension, polymorphonuclear leukocytes (PMN) were spherical and displayed a random array of recognition sites for all of the probes. PMN polarized in suspension by 10(-6) M N-formyl-L-methionyl-L-phenylalanine (f-Met-Phe), and PMN attached to substrate accumulated the bound lectin recognition site complex at the uropod (for Con A; 92.0 +/- 0.2% of cells and 91.3 +/- 9.8% of cells, respectively). Glutaraldehyde fixation of neutrophils oriented in a chemotactic gradient prior to lectin addition revealed the innate unbound recognition site array. Unbound Con A recognition sites were clustered at the front of 74.7 +/- 0.8% of cells in a "headlight" pattern, but binding sites for other lectins were distributed randomly around the polarized cell. When bound Con A complexes are swept to the tail of the polarized living PMN, "new" unbound Con A binding sites appear at the front of the cell. Neither cycloheximide nor KCN nor colchicine interferred with new binding site appearance. Cytochalasin B and sodium iodacetate prevented PMN polarization and interfered with appearance of new receptors. This suggests that these fresh sites are uncovered, previously cryptic binding sites rather than newly synthesized structures. Lectin binding site topography and movement are related to the functional state of the PMN. Since both Con A and certain bacteria bind to mannose derivatives, we postulate that the "headlight pattern" and uncovering of fresh binding sites aid the PMN in engulfing organisms as the phagocyte moves forward.

Invasive aspergillosis of the lung and pericardium in a nonimmunocompromised 33 year old man.

In a 33 year old man with no discernible immunologic defect, invasive aspergillosis developed in both the pericardium and lung with marked granulomatous reaction. The patient received 2 g of intravenous amphotericin B over eight weeks, with partial regression of the pulmonary infiltrate and disappearance of symptoms. However, five months later, he returned with marked progression of his disease. Evaluation of host defense, including granulocyte and lymphocyte function, was normal. The patient was given an additional 3g of amphotericin B over nine weeks with marked improvement in symptoms and chest roentgenogram. At six-month follow-up, he was asymptomatic with a stable radiographic appearance. A recurrence in symptoms and the pulmonary infiltrate was noted two months later. He was treated with an additional course of amphotericin and currently is receiving ketoconazole in hopes of suppressing the infection. We could find no immune impairment to explain the severe pulmonary and pericardial disease due to Aspergillus flavus in this young man.

Receptors for concanavalin A cluster at the front of polarized neutrophils.

Polymorphonuclear neutrophils (PMN) can recognize, engulf and kill microorganisms and are thus an important host defence against infection. The initial encounter between a microbe and the neutrophil takes place at the neutrophil surface. Receptors, including those for the Fc end of the immunoglobulin G (ref. 1), the C3b component of complement, formyl peptides and plant lectins have been identified on the surface of neutrophils. We have now examined the surface pattern and arrangement of receptors for the plant lectin concanavalin A (Con A) to determine if the surface receptor array varied with the functional state of the neutrophil. We found that receptors for Con A clustered at the front of polarized neutrophils.