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D M Musher

Publications and source records attributed to D M Musher.

At least 19 recordsLinked to original sources
PubMed2006

Analysis of mutations in the pbp genes of penicillin-non-susceptible pneumococci from Turkey.

Sequence analysis of the pbp genes from 20 Streptococcus pneumoniae isolates from Turkey (eight with high-level penicillin-resistance, nine with low-level penicillin-resistance, and three that were penicillin-susceptible) was performed and phylogenetic trees were constructed. Most isolates clustered together within a single branch that was distinct from sequences deposited previously in GenBank, which suggests that these isolates have probably evolved following new recombination events. The most prominent active-site mutations, which have also been associated previously with resistance, were T371A in PBP1a, E481G followed by T451A in PBP2b, and T338A in PBP2x. All isolates also possessed a (570)SVES/TK(574) block in the PBP2b sequence, instead of the QLQPT sequence of R6, which is fairly uncommon in GenBank sequences. This is the first study to analyse alterations in the pbp sequences of pneumococci isolated in Turkey.

Bacterial Proteins↗
PubMed2004

Response of HIV-infected patients with asymptomatic syphilis to intensive intramuscular therapy with ceftriaxone or procaine penicillin.

The objective of this prospective pilot study was to evaluate the response of HIV-infected patients with asymptomatic syphilis to one of two intensive antibiotic treatment regimens. Thirty-one HIV-infected patients with serum rapid plasma reagin titre > or =1:4 and no clinical findings of syphilis were randomized to receive daily intramuscular injections of ceftriaxone or procaine penicillin (plus oral probenecid) for 15 days; 24 returned for follow-up study. Seven of 10 (70%) procaine penicillin-treated patients and 10 of 14 (71%) ceftriaxone-treated patients had a > or =4-fold decline in RPR (P=0.94); two penicillin-treated and one ceftriaxone-treated patient relapsed. Two patients failed ceftriaxone therapy. Three penicillin-treated, and two ceftriaxone-treated patients were serofast. Serological responses were similar in those patients with and without asymptomatic neurosyphilis. There was no difference in the serologic response to daily treatment with ceftriaxone vs that with procaine penicillin plus probenecid; both treatments were associated with comparatively high rates of serological non-response and relapse.

Adult↗
PubMed2002

Safety and immunogenicity of 23-valent pneumococcal polysaccharide vaccine in HIV-1 infected former drug users.

The immunogenicity of 23-valent pneumococcal polysaccharide vaccine was assessed in 57 HIV-1 infected former intravenous drug users and in 20 HIV-1 negative controls. The effect of vaccination on HIV-1 infection was studied in a subgroup of 38 patients, 60% of whom under highly active antiretroviral therapy (HAART). Antibody to capsular polysaccharides from Streptococcus pneumoniae serotypes 3, 4, 6B, 19F, 23 F, and changes in CD4+ count, HIV-1 RNA, proviral DNA and HIV-1 phenotype were measured in pre- and post-vaccination samples. Vaccinations were well-tolerated. The rate of responders was higher (P<0.05) in HIV-1 negative than in HIV-1 infected individuals. No difference in antibody response was found within HIV-1 infected patients stratified according to CD4+ counts. Post-vaccination antibody geometric mean concentrations (GMCs) to the five antigens were higher (P<0.05) than baseline in HIV-1 negative subjects, but not in HIV-1 positive individuals. Those with CD4+ >500 cells/mm(3) showed a significant increase of antibody against type 3 only. Immunisation caused no significant changes in CD4+ counts and in either plasma HIV-1 RNA nor proviral DNA levels. Pneumococcal vaccination does not induce virological or immunological deterioration in HIV infected patients, but the antibody response to a single dose of vaccine is poor.

Adult↗
PubMed2001

A fresh look at the definition of susceptibility of Streptococcus pneumoniae to beta-lactam antibiotics.

Definitions for susceptibility or resistance of Streptococcus pneumoniae to penicillin were not developed until penicillin-resistant pneumococci appeared in South Africa in the late 1970s. The definition that was accepted (which still remains in use) and later definitions of resistance to most other beta-lactam antibiotics were derived from laboratory and clinical data relating to the treatment of meningitis, not otitis media, sinusitis, or pneumonia. An understanding of the origin of these definitions helps to resolve the apparent paradox that infections of the respiratory tract due to seemingly beta-lactam-resistant pneumococci may still respond well to standard doses of these drugs. A recently sanctioned change in the definition of susceptibility to amoxicillin is helpful in eliminating the paradox for this drug, but it may create further confusion by implying that, on a microgram basis, amoxicillin is substantially more effective than penicillin or third-generation cephalosporins. This article examines definitions of susceptibility and resistance of pneumococci, highlighting areas that have led to confusion and proposing a new way of understanding them.

Anti-Bacterial Agents↗
PubMed2001

Streptococcus intermedius, Streptococcus constellatus, and Streptococcus anginosus ("Streptococcus milleri group") are of different clinical importance and are not equally associated with abscess.

Difficulties in distinguishing organisms of the "Streptococcus milleri group" (SMG; Streptococcus intermedius, Streptococcus constellatus, and Streptococcus anginosus), have caused ambiguity in determining their pathogenic potential. We reviewed 118 cases in which SMG isolates had been identified using 16S rDNA sequence. S. constellatus and S. anginosus were isolated far more frequently than was S. intermedius. Nearly all isolates of S. intermedius and most isolates of S. constellatus, but only 19% of those of S. anginosus, were associated with abscess. Our findings suggest that speciation of the SMG may guide diagnostic evaluation, give insight into the possible role of coinfecting organisms, and help assess the need to search for occult abscess.

Abscess↗
PubMed2001

Nonspecificity of assaying for IgG antibody to pneumolysin in circulating immune complexes as a means to diagnose pneumococcal pneumonia.

Detection of immunoglobulin G (IgG) antibody to pneumolysin (PLY) in precipitated circulating immune complexes (CICs) has been used to diagnose pneumococcal pneumonia. With care to include appropriate controls, we precipitated and dissociated CICs and then assayed for IgG antibody to PLY. We detected IgG antibody to PLY in CICs that were precipitated from serum samples that were obtained at the time of admission to the hospital from 5 (23%) of 22 healthy adults, 7 (44%) of 16 subjects with stable chronic obstructive pulmonary disease, 10 (63%) of 16 subjects colonized with Streptococcus pneumoniae, and 9 (60%) of 15 patients with nonbacteremic pneumococcal pneumonia. Of the 16 patients with bacteremic pneumococcal pneumonia, 4 (25%) had IgG antibody to PLY at the time of admission, and 8 (50%) had IgG antibody to PLY in convalescence. Levels of IgG antibody in CICs closely correlated with serum levels of IgG antibody to PLY, implicating precipitation of free serum antibody in tests with false-positive results. Detection of IgG antibody to PLY in precipitated CICs is not a reliable method for diagnosing pneumococcal pneumonia.

Adult↗
PubMed2001

Protection against bacteremic pneumococcal infection by antibody to pneumolysin.

Pneumolysin is an important virulence factor of Streptococcus pneumoniae. This study examined the hypothesis that human antibody to pneumolysin provides protection against pneumococcal infection. At the time of hospital admission, patients with nonbacteremic pneumococcal pneumonia had higher levels of serum anti-pneumolysin IgG than did patients with bacteremic pneumococcal pneumonia or uninfected control subjects. IgG levels rose significantly during convalescence in patients with bacteremic pneumonia, reaching levels observed in nonbacteremic patients. Purified human anti-pneumolysin IgG protected mice against intraperitoneal challenge with S. pneumoniae types 1 or 4 in a dose-related fashion; mice that received anti-pneumolysin IgG had a greater likelihood of surviving challenge and had negative blood cultures. Pneumolysin damages epithelial cells and inhibits phagocytic function of polymorphonuclear leukocytes. One hypothesis that might explain the study results is that, early in infection, IgG to pneumolysin blocks these effects in the alveoli, thereby protecting the host against bacteremic pneumococcal disease.

Animals↗
PubMed2001

Antibiotic susceptibilities of genetically characterized Streptococcus milleri group strains.

Previous studies of the antibiotic susceptibility of Streptococcus milleri group organisms have distinguished among species by using phenotypic techniques. Using 44 isolates that were speciated by 16S rRNA gene sequencing, we studied the MICs and minimum bactericidal concentrations of penicillin, ampicillin, ceftriaxone, and clindamycin for Streptococcus intermedius, Streptococcus constellatus, and Streptococcus anginosus. None of the organisms was resistant to beta-lactam antibiotics, although a few isolates were intermediately resistant; one strain of S. anginosus was tolerant to ampicillin, and another was tolerant to ceftriaxone. Six isolates were resistant to clindamycin, with representation from each of the three species. Relatively small differences in antibiotic susceptibilities among species of the S. milleri group show that speciation is unlikely to be important in selecting an antibiotic to treat infection caused by one of these isolates.

Ampicillin↗
PubMed2000

Immunogenicity of pneumococcal vaccine in heart transplant recipients.

To assess the immunogenicity of pneumococcal vaccine in recipients of heart transplants, we immunized 35 long-term transplantation survivors with pneumococcal vaccine and measured the pre- and postvaccination IgG antibody titers to 5 representative vaccine capsular polysaccharides. Responses of heart transplant recipients to pneumococcal vaccine antigens were generally suppressed.

Adult↗
PubMed2000

Antibody to capsular polysaccharide of Streptococcus pneumoniae at the time of hospital admission for Pneumococcal pneumonia.

IgG to capsular polysaccharide (CPS) of Streptococcus pneumoniae is thought to provide the greatest degree of protection against pneumococcal disease. Serum obtained at hospital admission from 14 (27%) of 51 patients with bacteremic pneumococcal pneumonia and 11 (37%) of 30 with nonbacteremic pneumococcal pneumonia contained IgG to CPS of the infecting serotype; these percentages are similar to the prevalence of IgG to CPS in a control population. However, when compared with antibody from healthy adults, this IgG had far less capacity to opsonize the infecting pneumococcal serotype for phagocytosis in vitro by normal human polymorphonuclear leukocytes or to protect mice against experimental challenge. Failure to opsonize correlated closely with failure to protect mice, and each of these parameters correlated well with poor avidity for CPS. Future vaccine studies may need to examine the functional capacity of antibodies as a surrogate for infection, in addition to measuring their concentration in serum.

Animals↗
PubMed2000

Management of community-acquired pneumonia in the era of pneumococcal resistance: a report from the Drug-Resistant Streptococcus pneumoniae Therapeutic Working Group.

OBJECTIVE: To provide recommendations for the management of community-acquired pneumonia and the surveillance of drug-resistant Streptococcus pneumoniae (DRSP). METHODS: We addressed the following questions: (1) Should pneumococcal resistance to beta-lactam antimicrobial agents influence pneumonia treatment? (2) What are suitable empirical antimicrobial regimens for outpatient treatment of community-acquired pneumonia in the DRSP era? (3) What are suitable empirical antimicrobial regimens for treatment of hospitalized patients with community-acquired pneumonia in the DRSP era? and (4) How should clinical laboratories report antibiotic susceptibility patterns for S pneumoniae, and what drugs should be included in surveillance if community-acquired pneumonia is the syndrome of interest? Experts in the management of pneumonia and the DRSP Therapeutic Working Group, which includes clinicians, academicians, and public health practitioners, met at the Centers for Disease Control and Prevention in March 1998 to discuss the management of pneumonia in the era of DRSP. Published and unpublished data were summarized from the scientific literature and experience of participants. After group presentations and review of background materials, subgroup chairs prepared draft responses, which were discussed as a group. CONCLUSIONS: When implicated in cases of pneumonia, S pneumoniae should be considered susceptible if penicillin minimum inhibitory concentration (MIC) is no greater than 1 microg/mL, of intermediate susceptibility if MIC is 2 microg/ mL, and resistant if MIC is no less than 4 microg/mL. For outpatient treatment of community-acquired pneumonia, suitable empirical oral antimicrobial agents include a macrolide (eg, erythromycin, clarithromycin, azithromycin), doxycycline (or tetracycline) for children aged 8 years or older, or an oral beta-lactam with good activity against pneumococci (eg, cefuroxime axetil, amoxicillin, or a combination of amoxicillin and clavulanate potassium). Suitable empirical antimicrobial regimens for inpatient pneumonia include an intravenous beta-lactam, such as cefuroxime, ceftriaxone sodium, cefotaxime sodium, or a combination of ampicillin sodium and sulbactam sodium plus a macrolide. New fluoroquinolones with improved activity against S pneumoniae can also be used to treat adults with community-acquired pneumonia. To limit the emergence of fluoroquinolone-resistant strains, the new fluoroquinolones should be limited to adults (1) for whom one of the above regimens has already failed, (2) who are allergic to alternative agents, or (3) who have a documented infection with highly drug-resistant pneumococci (eg, penicillin MIC > or =4 microg/mL). Vancomycin hydrochloride is not routinely indicated for the treatment of community-acquired pneumonia or pneumonia caused by DRSP.

Adult↗
PubMed2000

Association between FcgammaRIIa-R131 allotype and bacteremic pneumococcal pneumonia.

Human FcgammaRIIa has 2 codominantly expressed allotypes, which differ greatly in their ability to ligate immunoglobulin G2 (IgG2). Whereas FcgammaRIIa-R131 binds only weakly to IgG2, FcgammaRIIa-H131 binds to it efficiently and might be primarily responsible for the phagocytosis of IgG2-opsonized bacteria. IgG2 plays a pivotal role in defense against pneumococcal infection. This prospective study showed that 50% of patients with bacteremic pneumococcal pneumonia were homozygous for FcgammaRIIa-R131, compared with 28% with nonbacteremic pneumococcal pneumonia and 29% of uninfected controls (P<.05). The gene frequency of FcgammaRIIa-R131 was 0.67 in bacteremic patients, significantly higher than in the other groups (P<.05). All bacteremic patients who died within 1 week of hospitalization were homozygous for FcgammaRIIa-R131. Therefore, the severity of pneumococcal infection may, in part, be genetically mediated. Taken together with similar findings in cases of meningococcal disease, these results suggest that such genetic factors may be generalizable to infections caused by encapsulated bacteria.

Alleles↗
PubMed2000

Bacteremic and nonbacteremic pneumococcal pneumonia. A prospective study.

We prospectively identified cases of pneumococcal pneumonia and used stringent criteria to stratify them into bacteremic and nonbacteremic cases. Although patients were distributed among racial groups in proportion to all patients seen at this medical center, the proportion of African-Americans with bacteremic disease was significantly increased. All patients had at least 1 underlying condition predisposing to pneumococcal infection, and most had several. Although the mean number of predisposing factors was greater among bacteremic patients than nonbacteremic patients, only alcohol ingestion was significantly more common. Nearly one-third of patients had substantial anemia (hemoglobin < or = 10 g/dL) on admission, which may have predisposed to infection. In the case of other laboratory abnormalities, such as albumin, creatinine, and bilirubin, it was difficult to determine which abnormality might have predisposed to pneumococcal infection and which might have resulted from it. The radiologic appearance was varied. Airspace consolidation and air bronchogram on chest X-ray were highly associated with bacteremic disease, as was the presence of pleural effusion. Although the Pneumonia Patient Outcomes Research Team (PORT) risk score was a predictor of mortality, it did not help to predict the presence of bacteremia in an individual case. Most patients who died in the first week in hospital were bacteremic, and a high PORT risk score with bacteremia reliably predicted a high likelihood of a fatal outcome. Eleven patients had extrapulmonary disease with meningitis, empyema, and septic arthritis predominating; all of these patients were bacteremic. The antibiotic susceptibility of our strains correlated well with those that have been reported in the United States during the years of this study. The use of numerous antibiotics of different classes in many patients, especially those who were the most ill, precluded analysis of outcome based on antibiotic therapy. Only 17 patients had been vaccinated. Since nearly all patients had conditions for which pneumococcal vaccine is recommended and more than one-third had been hospitalized in the preceding 6 months, the low rate of vaccination can be regarded as a missed opportunity to administer a potentially beneficial vaccine.

Adult↗