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Biomedical subjects

D M Musher

Publications and source records attributed to D M Musher.

At least 55 records · Page 3Linked to original sources
PubMed1996

The lack of association between aging and postvaccination levels of IgG antibody to capsular polysaccharides of Streptococcus pneumoniae.

One possible explanation for the apparently reduced efficacy of pneumococcal vaccine in elderly subjects is that IgG responses to pneumococcal capsular polysaccharides (PPSs) decline with aging. We administered pneumococcal vaccine to 118 adults who ranged in age from 20 to 93 years; 33 were > or = 70 years old. Four to 6 weeks later, we measured IgG reactive with PPSs from 10 commonly infecting serotypes of Streptococcus pneumoniae. By regression analysis, a slight but nonsignificant increase in anti-PPS IgG was observed with increased age for six serotypes and a nonsignificant decrease was observed for four. Mean IgG levels and the percentage of subjects with IgG levels > or = 1 microgram/mL were no different among persons > or = 70 years of age than among those < or = 69 years of age. These results show no consistent effect of aging on anti-PPS IgG levels 4-6 weeks after pneumococcal vaccination.

Adult↗
PubMed1996

Diagnosing and treating cytomegalovirus pneumonia in patients with AIDS.

Because cytomegalovirus (CMV) can be isolated from pulmonary secretions of human immunodeficiency virus (HIV)-infected patients without causing disease, its clinical significance as a cause of pneumonia in this patient population is frequently questioned. In a 22-month period, CMV pneumonia was diagnosed in 17 (8%) of 210 HIV-infected patients who underwent lung biopsy on the basis of microbiological and histologic criteria. The clinical presentations of these patients were nonspecific, including fever (100% of patients), shortness of breath (71%), cough (76%), and Pao2 of < 75 mm Hg (88%). A high correlation in the degree of viral burden in lung biopsy specimens was demonstrated by histologic examination, immunohistochemical analysis, and in situ hybridization. No other pulmonary pathogens were identified for nine patients, whereas other possible causes of pneumonia were present in eight: 11 patients had evidence of extrapulmonary CMV disease at presentation. Most patients initially responded to specific anti-CMV therapy; the overall mean survival +/- SD was 3.1 +/- 2.5 months. CMV should be considered as a possible cause of pneumonia in patients with advanced AIDS especially if CMV infection is documented at other sites.

AIDS-Related Opportunistic Infections↗
PubMed1996

Effect of human immunodeficiency virus type 1 infection on the antibody response to a glycoprotein conjugate pneumococcal vaccine: results from a randomized trial.

Adults (n = 282) were randomized to receive either a pneumococcal glycoprotein conjugate vaccine, composed of pneumococcal serotypes 6B, 14, 18C, 19F, and 23F linked to CRM197, or a 23-valent pneumococcal polysaccharide vaccine. Among human immunodeficiency virus (HIV)-uninfected persons, conjugate vaccine elicited significantly higher IgG antibody geometric mean titers (GMTs) than did polysaccharide vaccine for serotypes 6B, 18C, and 23F: IgG GMTs were 9.0 versus 4.8, 23.2 versus 5.9, and 15.3 versus 4.4 micrograms/mL, respectively. In contrast, the two vaccines elicited similar antibody GMTs in HIV-infected persons: GMTs ranged from 1.3 to 10.8 micrograms/mL for all serotypes. Of note, among persons receiving polysaccharide vaccine, antibody GMTs in HIV-uninfected and -infected persons with CD4 lymphocytes > or = 500/microL were similar. These data underscore the importance of controlled clinical evaluations of newer pneumococcal vaccines in all high-risk groups for whom pneumococcal immunization is recommended and highlight the need for early immunization of HIV-infected persons with currently available polysaccharide vaccines.

AIDS-Related Opportunistic Infections↗
PubMed1996

IgG antibody to pneumococcal capsular polysaccharide in human immunodeficiency virus-infected subjects: persistence of antibody in responders, revaccination in nonresponders, and relationship of immunoglobulin allotype to response.

Human immunodeficiency virus (HIV)-infected persons are less likely than are noninfected persons to respond to vaccination with pneumococcal polysaccharides (PPS). Among those who respond, however, similar IgG levels may be achieved. HIV-infected men immunized with pneumococcal vaccine were classified as high- or low-level responders (IgG > or = 1 microgram/mL for > or = 3 of 5 PPS [high] or for < or = 1 PPS [low]). One and 2 years after immunization, geometric mean IgG levels and the percentages of subjects with IgG levels > or = 1 microgram/mL were similar for HIV-infected and for healthy high-level responders (controls) for all PPS except for serotype 8. Among HIV-infected low-level responders, revaccination with a double dose of pneumococcal vaccine did not stimulate IgG responses. Responsiveness of HIV-infected white patients was significantly associated with the Km(1)- negative allotype. These findings support current general recommended guidelines for administering pneumococcal vaccine to HIV-infected persons. Nonresponders will not benefit from revaccination.

Adult↗
PubMed1996

Epitope mapping of B-cell determinants on the 15-kilodalton lipoprotein of Treponema pallidum (Tpp15) with synthetic peptides.

The antigenicity of the 15-kDa lipoprotein of Treponema pallidum (Tpp15 or TpN15) was comprehensively evaluated in epitope-scanning studies with overlapping deca- and octapeptides and polygonal rabbit and human infant immunoglobulins (Igs) and antisera. This approach enabled us to identify potentially important regions and to determine the optimal dilutions of Igs or antisera for use in further studies. IgM and IgG from both species were capable of recognizing multiple, continuous epitopes. A total of 13 peptides, principally clustered in the central regions of the protein, were recognized by all syphilitic sera and Ig fractions. On the basis of window analyses, frequency profiles, and alanine substitution studies, five heptapeptides were selected for mimetic studies. Two of these five immunodominant, continuous epitopes initially appeared to be species specific; however, antisera elicited against mimetics of all five epitopes were polyspecific, recognizing similar motifs on several other treponemal proteins, including those of avirulent organisms. The only mimetic which yielded positive reactions with infant IgM and syphilitic sera in the absence of cross-reactions with rabbit antisera to avirulent treponemes was the variant of the VMYASSG motif. These findings are relevant to the development of simple, inexpensive assays for the serodiagnosis of active syphilis.

Amino Acid Sequence↗
PubMed1995

Identification, cloning, and sequencing of DNA essential for encapsulation of Streptococcus pneumoniae.

This paper reports the cloning and sequencing of a region of DNA from Streptococcus pneumoniae serotype 3 surrounding transposon Tn916, insertion of which was previously shown to result in lack of expression of the extracellular capsule. Sequence analysis revealed that the transposon inserted into a consensus insertion site 71 bp from the 5' end of the cloned fragment. Within the clone, 3' downstream regions from two different pneumococcal lytA genes were identified, as well as a putative 194 AA open reading frame (ORF1). Moreover, two copies of the repeat element BOX, oriented in opposite directions, were located immediately 3' of orf1. Within the region bounded by the first pair of internal sequencing primers, analysis revealed that the fragment amplified by PCR was always of the same size. Moreover, Southern blotting showed that for all serotypes examined to date, homology exists with the cloned fragment. These results indicate that this region of the chromosome is highly conserved and, taken together with other independently derived data, suggest that interruptions or deletions within this DNA lead to unencapsulation.

Bacterial Capsules↗
PubMed1995

Pneumococcal virulence factors and host immune responses to them.

The principal virulence determinant of most encapsulated bacterial pathogens is the possession of an extracellular capsule. This paper discusses biological aspects of the Streptococcus pneumoniae capsule, putative roles played by accessory virulence factors of this pathogen and prospects for improvement of the currently available pneumococcal vaccine. Even though the interruption of genes encoding selected proteins has been shown to attenuate virulence to some degree, the physical removal of the pneumococcal capsule or the interruption of encapsulation genes completely abolishes virulence in mice. The role of the capsule in pathogenesis is not completely clear, however, since it is not known whether this structure is important in colonization, the obligatory first step in the process. In addition, a number of proteins have been implicated as possible accessory virulence factors. These include pneumolysin, two distinct neuraminidases, an IgA1 protease and two surface proteins, pspA and psaA. While interruption of the expression of some of these proteins examined to date has been shown to attenuate virulence, so far it has not proven possible to completely abolish virulence in this fashion. Proteinaceous accessory virulence factors may prove important to the development of second-generation pneumococcal vaccines, however. Pneumococcal and other proteins conjugated to pneumococcal polysaccharides are currently being evaluated as carriers in attempts to improve the immunogenicity of polysaccharide vaccines, primarily in small children.

Animals↗
PubMed1995

In vitro antimicrobial effect against Streptococcus pneumoniae of adding rifampin to penicillin, ceftriaxone, or 1-ofloxacin.

Adding rifampin to penicillin or l-ofloxacin diminished the rate at which these antibiotics killed 21 clinical isolates isolates of Streptococcus pneumoniae in vitro. A less pronounced inhibitory effect was observed when rifampin was added to ceftriaxone. Synergy was not observed for any bacterial isolate. The in vitro demonstration of indifference or antagonism using these antibiotic combinations argues against the empirical addition of rifampin to beta-lactams or fluoroquinolones in treating serious pneumococcal infections.

Anti-Bacterial Agents↗
PubMed1995

Antimicrobial activities of beta-lactam antibiotics and gentamicin against penicillin-susceptible and penicillin-resistant pneumococci.

The MICs of penicillin and cefotaxime for a range of penicillin-susceptible and penicillin-resistant isolates of Streptococcus pneumoniae were unchanged by the addition of gentamicin. In time-kill studies the rate of killing was greater for 18 of 20 isolates in the presence of gentamicin. However, mean differences in killing after 6 h of incubation were modest, not exceeding 1 log10 unit.

Anti-Bacterial Agents↗
PubMed1994

An epidemic of pneumococcal disease in an overcrowded, inadequately ventilated jail.

BACKGROUND: In the United States many correctional facilities now operate at far over capacity, with the potential for living conditions that permit outbreaks of respiratory infections. We investigated an outbreak that was identified in an overcrowded Houston jail after two inmates died of pneumococcal sepsis on the same day. Outbreaks of pneumococcal disease have been rare in the era of antibiotics. METHODS: We assessed risk factors for pneumococcal disease in both a case-control and a cohort study. Ventilation was evaluated by measuring carbon dioxide levels and air flow to the living areas of the jail. The extent of asymptomatic infection was determined by culturing pharyngeal specimens from a random sample of inmates. Type-specific immunity was determined with an enzyme immunoassay. RESULTS: Over a four-week period, 46 inmates had either acute pneumonia or invasive pneumococcal disease due to Streptococcus pneumoniae serotype 12F. The jail's capacity had been set at 3500 inmates, but it housed 6700 at the time of the outbreak; the inmates had a median living area of only 34 ft2 (3.2 m2) (interquartile range, 28 to 56 ft2 [2.6 to 5.2 m2]) per person. There were significantly fewer cases of disease among inmates with 80 ft2 (7.4 m2) per person or more (P = 0.030). Carbon dioxide levels ranged from 1100 to 2500 ppm (acceptable, < 1000), and the ventilation system delivered a median of only 6.1 ft3 of outside air per minute per person (interquartile range, 4.4 to 8.5 ft3; recommended, > or = 20 ft3). The attack rate was highest among inmates in cells with the highest carbon dioxide levels and the lowest volume of outside air delivered by the ventilation system (relative risk, 1.94; 95 percent confidence interval, 1.08 to 3.48). Of underlying medical conditions, intravenous drug use was most strongly associated with disease (odds ratio, 4.50). The epidemic strain (serotype 12F) was cultured from 7 percent of the asymptomatic inmates. Of 11 case patients tested with the enzyme immunoassay, 9 (82 percent) lacked preexisting immunity to this strain. CONCLUSIONS: Severe overcrowding, inadequate ventilation, and altered host susceptibility all contributed to this outbreak of pneumococcal disease in a large urban jail.

Adult↗
PubMed1994

Osteomyelitis associated with pressure sores.

BACKGROUND: Pressure sores may be associated with underlying osteomyelitis that is difficult to differentiate clinically from infection or colonization of adjacent soft tissue. Cultures of bone specimens are frequently contaminated with organisms residing in adjacent soft tissue. The three objectives of this cohort study were to (1) determine the accuracy of clinical evaluation for osteomyelitis; (2) evaluate the potential role of quantitative cultures of bone in differentiating osteomyelitis from soft-tissue infection or colonization; and (3) assess the impact of treating osteomyelitis on the outcome of pressure sores. METHODS: Thirty-six patients with pressure sores related to spinal cord injury or cerebrovascular accident underwent clinical evaluation for osteomyelitis, followed by percutaneous needle biopsy of bone. Routine semiquantitative and quantitative, aerobic and anaerobic cultures of bone specimens were performed. Pathologic examination of bone tissue was used as the standard criterion for diagnosing osteomyelitis. RESULTS: Six (17%) of 36 patients were diagnosed by pathologic examination as having osteomyelitis. The sensitivity and specificity of clinical evaluation were 33% and 60%, respectively. When positive, quantitative bone cultures yielded a similar number of bacterial isolates and a comparable range of bacterial concentration in patients with osteomyelitis vs those without osteomyelitis. Pressure sores healed in all six patients with osteomyelitis after appropriate therapy. CONCLUSIONS: Clinical evaluation for osteomyelitis is often inaccurate. Pathologic examination of bone tissue is required for definitive diagnosis of osteomyelitis. Quantitative bone cultures do not help differentiate osteomyelitis from infection or colonization of adjacent soft tissue. It is possible that treatment of osteomyelitis may improve the outcome of associated pressure sores.

Biopsy↗
PubMed1994

Vancomycin penetration into biofilm covering infected prostheses and effect on bacteria.

To evaluate the adequacy of penetration of antibiotics into biofilm, a novel in vitro model for prosthesis-related infection was developed. Sterile stainless steel orthopedic nuts were incubated with slime-producing Staphylococcus epidermidis. Biofilm-covered nuts were exposed to varying concentrations of vancomycin; then biofilms were harvested. Vancomycin levels in biofilm, as measured by fluorescent polarization immunoassay, far exceeded the MIC and MBC of vancomycin for the organism. Bacterial growth in biofilm was inversely related to vancomycin concentration in biofilm, but even extremely high drug concentrations did not eradicate bacteria embedded in biofilm. The MICs and MBCs for bacteria recovered from biofilm did not differ from those for incubating organisms. Thus, failure of glycopeptide antibiotics to cure prosthesis-related infection is not due to poor penetration of drugs into biofilm but likely due to diminished antimicrobial effect on bacteria in the biofilm environment.

Bioprosthesis↗