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Biomedical subjects

Daniel M Musher

Publications and source records attributed to Daniel M Musher.

At least 19 recordsLinked to original sources
PubMed2006

Community-associated strains of methicillin-resistant Staphylococccus aureus as the cause of healthcare-associated infection.

OBJECTIVE: Methicillin-resistant Staphylococcus aureus (MRSA) isolates from patients with community-associated infection have been described as strains genetically distinct from the strains isolated from patients with healthcare-associated infection. This study examines the hypothesis that community-associated MRSA (CA-MRSA) strains now cause serious infections in hospitalized patients. METHODS: Thirty-seven clinical MRSA isolates were randomly selected from blood isolates obtained from July 2003 through June 2004. Strains were tested for staphylococcal chromosomal cassette mec (SCCmec) type, pulsed-field gel electrophoresis (PFGE) type, and presence of Panton-Valentine leukocidin (PVL) genes. Medical records review and epidemiologic classification was performed by an investigator blinded to the results of the bacterial strain analysis. Episodes of bloodstream infection were independently classified as either community-associated or healthcare-associated infections, and bacterial isolates were independently classified as either CA-MRSA strains or healthcare-associated MRSA (HA-MRSA) strains, according to established definitions. SETTING: A tertiary care Veterans Affairs Medical Center. RESULTS: Twenty-four (65%) of 37 MRSA isolates were SCCmec type IV, a genetic type characteristic of CA-MRSA strains; 22 of these 24 isolates belonged to the CA-MRSA clone USA300 and carried PVL genes. Thirteen (35%) of the 37 strains were SCCmec type II, of which 12 were USA100-ST5 and 12 lacked PVL genes. Thirty patients (81%) had healthcare-associated infections; 18 (60%) of these 30 were infected with isolates carrying markers of CA-MRSA strains. Of 7 patients with CA-MRSA infections, 6 were infected with isolates belonging to the USA300 clone. Patients with healthcare-associated bloodstream infections were as likely to be infected with a CA-MRSA strain as patients with a community-associated infection (P = .38). CONCLUSIONS: MRSA strains with molecular characteristics of CA-MRSA strains have emerged as an important cause of serious healthcare-associated infection in our hospital.

Adult↗
PubMed2006

Effect of pneumococcal vaccination: a comparison of vaccination rates in patients with bacteremic and nonbacteremic pneumococcal pneumonia.

BACKGROUND: Despite the widespread acceptance of the 23-valent pneumococcal capsular polysaccharide vaccine (PPV), its protective effect continues to be disputed. We describe a novel approach to examine the protective effect of this vaccine. METHODS: We recorded the vaccination status of every patient for whom a culture yielded Streptococcus pneumoniae during a 4.5-year period, comparing rates of prior PPV administration in patients with (1) bacteremic pneumococcal pneumonia, (2) all-invasive pneumococcal disease, (3) nonbacteremic pneumococcal pneumonia, (4) acute exacerbation of chronic bronchitis (AECB) due to S. pneumoniae, and (5) pneumococcal colonization. The principal comparisons were with patients who had bacteremic pneumonia or any invasive pneumococcal disease and those with nonbacteremic pneumococcal pneumonia. We also compared vaccination rates in patients who had nonbacteremic pneumonia with vaccination rates in patients with AECB or pneumococcal colonization. RESULTS: The rate of prior PPV vaccination was lower among patients with bacteremic pneumococcal pneumonia (39.7%) or any invasive pneumococcal disease (38.0%) than among patients with nonbacteremic pneumonia (57.6%), AECB (60.0%), or pneumococcal colonization (57.8%). PPV conferred a 54% protection rate against bacteremic versus nonbacteremic pneumococcal pneumonia. There was no apparent protection against nonbacteremic pneumonia compared, for example, with colonized persons or with those who had AECB. CONCLUSIONS: PPV provides moderate protection against invasive pneumococcal disease but does not protect against nonbacteremic pneumococcal pneumonia. These findings suggest the importance of a continued search for a better pneumococcal vaccine.

Aged↗
PubMed2006

Bactericidal activity of orally available agents against methicillin-resistant Staphylococcus aureus.

BACKGROUND: The recent proliferation of community-acquired (CA) methicillin-resistant Staphylococcus aureus (MRSA) has led to a marked increase in the need for outpatient treatment of MRSA infections. Many oral agents active against MRSA have been available for years, and a paucity of literature compares them, leaving physicians with little guidance for choosing among them. The purpose of the present study was to compare the bactericidal effects of orally available antibiotics against MRSA and to determine whether there were differences in antimicrobial killing activity against CA-MRSA and hospital-acquired (HA) MRSA isolates. METHODS: A total of 12 unique patient MRSA isolates were studied. Six strains were CA, carrying the staphylococcal chromosomal cassette (SCCmec) type IVa, while six were HA and carried SCCmec type II. Time-kill methods were used to study the bactericidal activity of the orally available antimicrobials linezolid, rifampicin, trimethoprim/sulfamethoxazole, clindamycin, minocycline, and moxifloxacin alone and in combination in vitro. RESULTS: Trimethoprim/sulfamethoxazole was rapidly bactericidal resulting in >2 log(10) cfu/mL decrease at 8 h and >3 log(10) cfu/mL decrease at 24 h in vitro. No antibiotic combination exhibited better killing than trimethoprim/sulfamethoxazole alone. Adding rifampicin to trimethoprim/sulfamethoxazole showed a trend towards antagonism in vitro. There were no differences in the bactericidal activity of any antimicrobial or antimicrobial combination against MRSA isolates carrying SCCmec type IVa versus those carrying SCCmec type II. CONCLUSION: Trimethoprim/sulfamethoxazole is rapidly bactericidal against MRSA in vitro when compared with most other orally available antimicrobials. No differences in bactericidal activity were detected when activities against CA-MRSA and HA-MRSA were compared.

Administration, Oral↗
PubMed2006

Nitazoxanide for the treatment of Clostridium difficile colitis.

BACKGROUND: Clostridium difficile colitis has increased in incidence and severity, and treatment failure with metronidazole therapy has increasingly been documented. It is uncertain whether treatment with vancomycin is more effective than treatment with metronidazole, but concern over the emergence of vancomycin resistance has motivated the search for alternative therapy. Nitazoxanide, a nitrothiazolide, blocks anaerobic metabolism of eukaryocyes and effectively treats intestinal infestation due to Cryptosporidium or Giardia species. At low concentrations, this compound inhibits C. difficile in vitro. METHODS: We designed a prospective, randomized, double-blind study to compare nitazoxanide to metronidazole in treating hospitalized patients with C. difficile colitis. RESULTS: Thirty-four patients received metronidazole at a dosage of 250 mg 4 times per day for 10 days, 40 patients received nitazoxanide at a dosage of 500 mg 2 times per day for 7 days, and 36 patients received nitazoxanide at a dosage of 500 mg 2 times per day for 10 days. After 7 days of treatment, 28 (82.4%) of 34 patients had responded to metronidazole therapy, compared with 68 (89.5%) of 76 who had received nitazoxanide therapy (difference, 7.1%; 95% confidence interval, -7.1% to 25.5%). Thirty-one days after beginning treatment, sustained responses were observed in 19 (57.6%) of 33 patients who had received metronidazole therapy for 10 days, compared with 25 (65.8%) of 38 who had received nitazoxanide for 7 days and 26 (74.3%) of 35 who had received nitazoxanide for 10 days (P = .34). CONCLUSION: Nitazoxanide is at least as effective as metronidazole in treating C. difficile colitis.

Aged↗
PubMed2006

Computerized tomography (CT)-guided aspiration of abscesses: outcome of therapy at a tertiary care hospital.

OBJECTIVE: To review the experience with percutaneous aspiration of abscesses at a general, tertiary care hospital from 2000 to 2005. METHODS: Computerized medical records of 90 patients who underwent radiologically guided drainage of 92 fluid collections were reviewed for demographic data, co-morbid conditions, location, radiographic imaging characteristics and culture results and to determine the long-term outcome of the procedure. RESULTS: Sixty-seven of 92 (73%) abscesses were cured without the need for open surgical drainage; 44 were cured within 14 days, and 23 had delayed resolution requiring prolonged antibiotics and/or a second drainage. Of the abscesses 85% were drained using a catheter in situ, the remaining aspirated using a needle. Twenty-five (27%) of the 92 abscesses failed percutaneous drainage, requiring open surgical drainage or lead to sepsis and death. Neither co-morbid conditions nor the location of abscesses affected the outcome of drainage. Patients who had sterile cultures of aspirated material after receiving antibiotics prior to the procedure had a significantly higher cure rate than otherwise (P<0.05). Catheter drainage was associated with a significantly higher cure rate than was needle aspiration (P<0.05). CONCLUSION: Percutaneous drainage, along with appropriate antibiotics, is an effective approach to treat deep abscesses. Drainage, itself, is the major determinant of outcome, rather than the location, characteristics of the abscess or condition of the patient prior to the procedure.

Abscess↗
PubMed2006

An update on diagnosis, treatment, and prevention of Clostridium difficile-associated disease.

Clostridium difficile is an important cause of nosocomial morbidity and mortality and is implicated in recent epidemics. Data support the treatment of colitis with oral metronidazole in a dose of 1.0 to 1.5 g/d, with oral vancomycin as a second-line agent, not because its efficacy is questioned but because of environmental concerns. Nitazoxanide and other drugs are currently under intense study as alternatives. Treatment of asymptomatic patients is not recommended. Current management strategies appear to be increasingly ineffective, especially for patients who experience multiple recurrences. Biotherapy and vaccination are currently being explored as treatment options for patients who have recurrent disease. Greater attention should be paid to hospital infection control policies and restriction of broad-spectrum antibiotics.

Clostridioides difficile↗
PubMed2006

Clostridium difficile lacks detectable superantigen activity.

Clostridium difficile colitis causes striking leukocytosis. We examined the possibility that toxins A or B, or other nontoxin products of C. difficile, act as superantigens, thereby stimulating leukocytosis. Our results failed to show major histocompatibility complex class II-dependent T lymphocyte proliferation, the hallmark of superantigen activity. Elevated white blood cell counts in C. difficile colitis are probably due to increased generation of cytokines such as interleukin-6 (IL-6) or IL-8.

Animals↗
PubMed2006

Nontypeable Haemophilus influenzae as a cause of spontaneous bacterial peritonitis.

Haemophilus influenzae rarely causes spontaneous bacterial peritonitis. We describe a typical case of spontaneous bacterial peritonitis in which the causative organism was identified as nontypeable H. influenzae, biotype III. Infection progressed despite the presence of adequate serum bactericidal antibody, probably due to the absence of complement in ascites fluid.

Animals↗
PubMed2005

Relatively poor outcome after treatment of Clostridium difficile colitis with metronidazole.

BACKGROUND: Clostridium difficile is a frequent cause of serious nosocomial infection. Earlier reports have suggested that treatment with metronidazole cured nearly 90% of patients, with only a modest rate of recurrence of infection. In recent years, the rate of response to treatment with this drug has appeared to be much lower. METHODS: We undertook a prospective, observational study of 207 patients who were treated with metronidazole for C. difficile colitis. RESULTS: A total of 103 patients (50%) were cured by the initial course of therapy and had no recurrence of disease. Forty-six patients (22%) continued to have symptoms of colitis for > or = 10 days despite treatment, and 58 (28%) responded initially but had a recurrence within the ensuing 90 days. The mortality rate among patients who developed C. difficile colitis was 27%, and it was higher among patients who did not respond fully to an initial course of therapy, compared with those who did (33% vs. 21%; P < .05). CONCLUSIONS: Because of the relatively poor response to therapy, additional approaches to prevention and/or treatment of C. difficile colitis appear to be warranted.

Anti-Bacterial Agents↗
PubMed2005

Administration of protein-conjugate pneumococcal vaccine to patients who have invasive disease after splenectomy despite their having received 23-valent pneumococcal polysaccharide vaccine.

Patients who undergo splenectomy are at greatly increased risk for overwhelming pneumococcal bacteremia and death. Twenty-three-valent pneumococcal polysaccharide vaccine (PPV-23), which contains capsular polysaccharides (PSs) from 23 common serotypes of Streptococcus pneumoniae, is strongly recommended for such patients. The capacity to respond to PPV-23 by producing immunoglobulin (Ig) G is genetically regulated. Some proportion of adults do not respond and, despite postsplenectomy administration of PPV-23, may remain susceptible to recurrent pneumococcal sepsis. Here, we describe 2 patients who had recurring pneumococcal bacteremia after undergoing splenectomy despite having received numerous doses of PPV-23. Heptavalent protein-conjugate pneumococcal vaccine (PCPV-7) was then administered, and it induced high levels of IgG to all 7 PSs; in one of the patients, functional activity against 5 of the 7 PSs was demonstrable, both in vitro and in vivo. Recurrent pneumococcal bacteremia in patients who have undergone splenectomy may indicate a genetically regulated failure to respond to PPV-23; PCPV-7 may stimulate production of IgG to PSs in such patients.

Adult↗
PubMed2005

Treatment of Clostridium difficile-associated disease: old therapies and new strategies.

Clostridium difficile-associated disease (CDAD) causes substantial morbidity and mortality. The pathogenesis is multifactorial, involving altered bowel flora, production of toxins, and impaired host immunity, often in a nosocomial setting. Current guidelines recommend treatment with metronidazole; vancomycin is a second-line agent because of its potential effect on the hospital environment. We present the data that led to these recommendations and explore other therapeutic options, including antimicrobials, antibody to toxin A, probiotics, and vaccines. Treatment of CDAD has increasingly been associated with failure and recurrence. Recurrent disease may reflect relapse of infection due to the original infecting organism or infection by a new strain. Poor antibody responses to C difficile toxins have a permissive role in recurrent infection. Hospital infection control and pertinent use of antibiotics can limit the spread of CDAD. A vaccine directed against C difficile toxin may eventually offer a solution to the CDAD problem.

Anti-Infective Agents↗
PubMed2005

Secondary syphilitic lesions.

An important theme that emerges from all early historical accounts is that in addition to the decreased virulence of Treponema pallidum, the incidence of secondary syphilis has decreased drastically over the past three centuries. Even in the early 20th century, most syphilologists were of the opinion that the disease had undergone changes in its manifestations and that they were dealing with an attenuated form of the spirochete. Such opinions were based primarily on the observations that violent cutaneous reactions and fatalities associated with the secondary stage had become extremely rare. The rate of primary and secondary syphilis in the United States increased in 2002 for the second consecutive year. After a decade-long decline that led to an all-time low in 2000, the recent trend is attributable, to a large extent, by a increase in reported syphilis cases among men, particularly homosexual and bisexual men having sex with men. The present review addresses the clinical and diagnostic criteria for the recognition of secondary syphilis, the clinical course and manifestations of the disease if allowed to proceed past the primary stage of disease in untreated individuals, and the treatment for this stage of the disease.

Chronic Disease↗