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Biomedical subjects

Daniel M Musher

Publications and source records attributed to Daniel M Musher.

36 records · Page 2Linked to original sources

Diagnostic value of microscopic examination of Gram-stained sputum and sputum cultures in patients with bacteremic pneumococcal pneumonia.

Clinicians continue to question the usefulness of microscopic examination of Gram-stained sputum specimens ("Gram staining") and sputum culture for diagnosis of pneumonia. We analyzed the sensitivity of these techniques in 105 patients with pneumococcal pneumonia proven by blood culture. Gram staining revealed gram-positive cocci in pairs and chains, and culture yielded pneumococci in only 31% and 44% of all cases, respectively. However, sputum specimens were never submitted for examination in 31 cases; in 16 others, the specimen was inadequate and a culture was not done. Excluding these cases, the sensitivities of Gram staining and culture were 57% and 79%, respectively. If patients receiving antibiotics for >24 h had been excluded, Gram staining would have suggested pneumococci in 63%, and culture results would have been positive in 86%. Sensitivity increased in inverse proportion to the duration of antibiotic therapy (P<.05). Microscopic examination of sputum samples before antibiotics were administered and performance of culture within 24 h of receipt of such treatment yielded the correct diagnosis in >80% of cases of pneumococcal pneumonia.

Anti-Bacterial Agents↗

In vitro killing of community-associated methicillin-resistant Staphylococcus aureus with drug combinations.

This study employs time-kill techniques to examine the most common drug combinations used in the therapy of methicillin-resistant Staphylococcus aureus (MRSA) infections, vancomycin plus either gentamicin or rifampin. Community-associated MRSA were more likely to be synergistically inhibited by combinations of vancomycin and gentamicin versus vancomycin alone compared to inhibition associated with hospital-acquired strains.

Community-Acquired Infections↗

Rickettsia sibirica infection in members of scientific expeditions to northern Asia.

The risk of acquiring North Asian tick typhus (infection by Rickettsia sibirica) during travel to regions of Asia where this disease is endemic is unknown. We investigated prospectively 13 paleontologists on expedition to Mongolia. Four paleontologists had acute illness characterised by fever, rash, headache, and lymphadenopathy. All had IgM and IgG antibodies to R sibirica. Paleontologists with no illness and people who went on expeditions in other parts of the world did not have antibodies to R sibirica. Only two of the four infected persons were aware of tick bites. Travellers to regions endemic for R sibirica are at risk of contracting North Asian tick typhus even in the absence of recognised tick-bites.

Aldehyde Oxidoreductases↗

Response of human immunodeficiency virus-infected patients receiving highly active antiretroviral therapy to vaccination with 23-valent pneumococcal polysaccharide vaccine.

Whether highly active antiretroviral therapy (HAART) impacts responses to 23-valent pneumococcal polysaccharide vaccine (PV) is not known. Immunoglobulin G (IgG) levels for 6 capsular polysaccharides in human immunodeficiency virus (HIV)-infected patients who had received > or =6 months of HAART were measured either after their first dose of PV (n=46) or after revaccination (n=41); control subjects had never received HAART and had received the first dose of PV (n=38). There were no significant differences in pre- or postvaccination IgG levels among these groups but for 1 capsular polysaccharide. The 3 groups had significant postvaccination increases in IgG levels to all capsular polysaccharides. The control group had a greater number of 2-fold responses than did the combined HAART groups (P<.05). Patients with a CD4 cell count of > or =200 cells/mm3 had a greater number of 2-fold responses than did those with a CD4 cell count of <200 cells/mm3 (P<.05). For revaccinated patients, postvaccination IgG levels were correlated with the CD4 cell count at the initial vaccination. The immunogenicity of PV among patients receiving long-term HAART is modest. It seems best to immunize HIV-infected patients early in the course of disease.

Adult↗

Spectrum of bacille Calmette-Guérin (BCG) infection after intravesical BCG immunotherapy.

Intravesical instillation of bacille Calmette-Guérin (BCG) effectively treats transitional cell carcinoma of the bladder. Occasionally, BCG infection complicates such treatment. In some patients, infection appears early (within 3 months after instillation) and is characterized by generalized symptoms, with pneumonitis and hepatitis. Late-presentation disease occurs >1 year after the first BCG treatment and usually involves focal infection of the genitourinary tract (the site at which bacteria were introduced) and/or other sites that are typical for reactivation of mycobacterial disease, such as the vertebral spine or the retroperitoneal tissues. Noncaseating granulomas are found in the majority of cases, whether early or late. Most patients respond to treatment with antituberculous drugs; in early-presentation disease, when features of hypersensitivity predominate, glucocorticosteroids are sometimes added. Late localized infection often requires surgical resection.

Adult↗

Clostridium difficile infection in patients with unexplained leukocytosis.

PURPOSE: To determine whether unrecognized Clostridium difficile infection is responsible for a substantial proportion of cases of unexplained leukocytosis in a tertiary care hospital setting. METHODS: We prospectively identified 60 patients who had unexplained leukocytosis (white blood cell count > or =15,000/mm3). Fecal specimens were tested for C. difficile toxin using an enzyme immunosorbent assay. We compared the clinical features of patients who had positive or negative assay results, as well as of 26 hospitalized control patients who did not have unexplained leukocytosis. RESULTS: Thirty-five (58%) of the patients with unexplained leukocytosis had C. difficile toxin in at least one fecal specimen as compared with 3 (12%) of the controls (P <0.001). Symptoms of colitis were often mild or absent at the time the white blood cell count was first elevated or, if present, had not been recognized by the attending physicians. Leukocytosis resolved promptly in most patients who were treated with metronidazole. In the 25 patients (42%) who had a negative test for C. difficile toxin, leukocytosis also tended to resolve during empiric therapy with metronidazole; some of these patients may have had C. difficile infection. CONCLUSION: The majority of patients in our hospital who had unexplained leukocytosis had C. difficile infection. Unexplained leukocytosis in hospitalized patients should prompt a search for symptoms and signs consistent with C. difficile infection and a study to detect C. difficile. Empiric therapy with metronidazole may be effective in the appropriate epidemiologic setting.

Anti-Infective Agents↗

Surgical versus nonsurgical treatment of empyema thoracis: an outcomes analysis.

BACKGROUND: Empyema thoracis (ET) is associated with substantial morbidity and mortality. The optimal means for draining the pleural space remains controversial but there may be increasing bias for less invasive strategies. This study compared outcome after a nonsurgical versus a surgical approach to ET. METHODS: Patients with ET over a 10-year period (n = 93) were reviewed and stratified into nonsurgical (thoracentesis and/or closed tube thoracostomy) and surgical (thoracotomy, decortication, and/or open window thoracostomy) groups based on pleural drainage techniques. Hospital course was analyzed except when altered by death (n = 12), noncompliance (n = 3), or severe comorbidities (n = 3). RESULTS: Seventy-five patients were stratified into nonsurgical (n = 32) and surgical (n = 43) groups. Demographics, comorbidities, signs and symptoms, and causative organisms were similar between groups. Mortality did not significantly differ in nonsurgical (16%) versus surgical (10%) groups (P = 0.7). Although delay in diagnosis and number of therapeutic interventions were nearly identical, the time to definitive therapy was longer in the surgical versus the nonsurgical group (18 +/- 3.8 versus 8.5 +/- 3.8 days, P = 0.023). The time to discharge after definitive therapy (20.0 +/- 3.5 versus 35.6 +/- 14.0 days, P < 0.001), and overall hospital stay (40.6 +/- 5.3 versus 47.4 +/- 15 days, P = 0.01) was significantly decreased in the surgical versus nonsurgical treatment groups, respectively. CONCLUSION: The treatment of ET is complex. Failure to adequately evacuate the pleural space and/or persistent signs of infection should prompt surgical intervention. Surgical therapy is preferred for advanced stages of ET. Delaying definitive surgical treatment is largely responsible for prolonging hospital course.

Adult↗

Staphylococcus aureus bacteremia: recurrence and the impact of antibiotic treatment in a prospective multicenter study.

Staphylococcus aureus bacteremia is associated with substantial morbidity. Recurrence is common, but incidence and risk factors for recurrence are uncertain. The emergence of methicillin resistance and the ease of administering vancomycin, especially in patients who have renal insufficiency, have led to reliance on this drug with the assumption that it is as effective as beta-lactam antibiotics, an assumption that remains open to debate. We initiated a multicenter, prospective observational study in 6 university hospitals and enrolled 505 consecutive patients with S. aureus bacteremia. All patients were monitored for 6 months and patients with endocarditis were followed for 3 years. Recurrence was defined as return of S. aureus bacteremia after documentation of negative blood cultures and/or clinical improvement after completing a course of antistaphylococcal antibiotic therapy. All blood isolates taken from patients with recurrent bacteremia underwent pulsed-field gel electrophoresis testing. Recurrence was subclassified as reinfection (different pulsed-field gel electrophoresis patterns) or relapse (same pulsed-field gel electrophoresis pattern).Forty-two patients experienced 56 episodes of recurrence (79% were relapses and 21% were reinfection). Relapse occurred earlier than reinfection (median, 36 versus 99 d, p < 0.06). Risk factors for relapse of S. aureus bacteremia included valvular heart disease, cirrhosis of the liver, and deep-seated infection (including endocarditis). Nafcillin was superior to vancomycin in preventing bacteriologic failure (persistent bacteremia or relapse) for methicillin-susceptible S. aureus (MSSA) bacteremia. Failure to remove infected intravascular devices/catheters and vancomycin therapy were common factors in patients experiencing multiple (greater than 2) relapses. However, by multivariate analysis, only endocarditis and therapy with vancomycin (versus nafcillin) were significantly associated with relapse. Recurrences occurred in 9.4% of S. aureus bacteremias following antistaphylococcal therapy, and most were relapses. Duration of antistaphylococcal therapy was not associated with relapse, but type of antibiotic therapy was. Nafcillin was superior to vancomycin in efficacy in patients with MSSA bacteremia.

Adolescent↗

A prospective multicenter study of Staphylococcus aureus bacteremia: incidence of endocarditis, risk factors for mortality, and clinical impact of methicillin resistance.

Our objectives were to determine the incidence of endocarditis in patients whose Staphylococcus aureus bacteremia was community-acquired, related to hemodialysis, or hospital-acquired; to assess clinical factors that would reliably distinguished between S. aureus bacteremia and S. aureus endocarditis; to assess the emergence of methicillin-resistant S. aureus (MRSA) as a cause of endocarditis; and to examine risk factors for mortality in patients with S. aureus endocarditis. We conducted a prospective observational study in 6 university teaching hospitals; we evaluated 505 consecutive patients with Staphylococcus aureus bacteremia. Thirteen percent of patients with S. aureus bacteremia were found to have endocarditis, including 21% with community-acquired S. aureus bacteremia, 5% with hospital-acquired bacteremia, and 12% on hemodialysis. Infection was due to MRSA in 31%. Factors predictive of endocarditis included underlying valvular heart disease, history of prior endocarditis, intravenous drug use, community acquisition of bacteremia, and an unrecognized source. Twelve patients with bacteremia had a prosthetic valve; 17% developed endocarditis. Unexpectedly, nonwhite race proved to be an independent risk factor for endocarditis by both univariate and multivariate analyses. Persistent bacteremia (positive blood cultures at day 3 of appropriate therapy) was identified as an independent risk factor for both endocarditis and mortality, a unique observation not reported in other prospective studies of S. aureus bacteremia. Patients with endocarditis due to MRSA were significantly more likely to have complicating renal insufficiency and to experience persistent bacteremia than those with endocarditis due to MSSA. The 30-day mortality was 31% among patients with endocarditis compared to 21% in patients who had bacteremia without endocarditis (p = 0.055). Risk factors for death due to endocarditis included severity of illness at onset of bacteremia (as measured by Apache III and Pitt bacteremia score), MRSA infection, and presence of atrioventricular block on electrocardiogram. Patients with S. aureus bacteremia who have community acquisition of infection, underlying valvular heart disease, intravenous drug use, unknown portal of entry, history of prior endocarditis, and possibly, nonwhite race should undergo echocardiography to screen for the presence of endocarditis. We recommend that blood cultures be repeated 3 days following initiation of antistaphylococcal antibiotic therapy in all patients with S. aureus bacteremia. Positive blood cultures at 3 days may prove to be a useful marker in promoting more aggressive management, including more potent antibiotic therapy and surgical resection of the valve in endocarditis cases. MRSA as the infecting organism should be added to the list of risk factors for consideration of valvular resection in cases of endocarditis.

Bacteremia↗

Conditions associated with leukocytosis in a tertiary care hospital, with particular attention to the role of infection caused by clostridium difficile.

Few modern studies have enumerated the conditions associated with leukocytosis. Our clinical experience has implicated Clostridium difficile infection in a substantial proportion of patients with leukocytosis. In a prospective, observational study of 400 inpatients with WBC counts of >/=15,000 cells/mm(3), we documented >/=1 infection in 207 patients (53%). Of these 207 patients, 97 (47%) had pneumonia, 60 (29%) had urinary tract infection, 34 (16%) had soft-tissue infection, and 34 (16%) had C. difficile infection. C. difficile infection was present in 25% of patients with WBC counts of >30,000 cells/mm(3) who did not have hematological malignancy. Other causes of leukocytosis in the 400 patients included physiological stress, in 152 patients (38%); medications or drugs, in 42 (11%); hematological disease, in 22 (6%); and necrosis or inflammation, in 22 (6%). C. difficile infection is a prominent cause of leukocytosis and this diagnosis should be considered for patients with WBC counts of >/=15,000 cells/mm(3), even in the absence of diarrheal symptoms.

Adult↗

Interaction between human polymorphonuclear leukocytes and Streptococcus milleri group bacteria.

Because Streptococcus milleri group (SMG) bacteria--Streptococcus constellatus, Streptococcus intermedius, and Streptococcus anginosus--exhibit a striking propensity to cause abscesses, the interaction of these organisms with human polymorphonuclear leukocytes (PMNL) was examined. After incubation in pooled normal human serum, SMG stimulated less chemotaxis than did Staphylococcus aureus, in contrast to viridans streptococci, which caused greater chemotaxis than did S. aureus. PMNL ingested greater numbers of SMG and viridans streptococci than S. aureus but killed these organisms more slowly and less completely. Relative resistance to killing by PMNL is expected in organisms that cause abscesses, and inhibition of chemotaxis may contribute to pathogenicity, because delayed arrival of PMNL gives a head start to proliferating bacteria. This study helps explain the capacity of SMG to cause abscesses. It is unclear, however, why viridans streptococci, bacteria that rarely produce abscesses, share some of these same properties.

Abscess↗