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Biomedical subjects

V K Dhawan

Publications and source records attributed to V K Dhawan.

At least 19 recordsLinked to original sources

Thrombin-induced platelet microbicidal protein susceptibility phenotype influences the outcome of oxacillin prophylaxis and therapy of experimental Staphylococcus aureus endocarditis.

We previously showed that in vitro susceptibility profiles of Staphylococcus aureus to thrombin-induced platelet microbicidal protein 1 (tPMP-1) impacted the outcome of vancomycin treatment in experimental infective endocarditis. In this same model, treatment with oxacillin (a more rapid staphylocidal agent than vancomycin) enhanced the clearance of both tPMP-1-susceptible and -resistant cells from vegetations. The extent of clearance was greater for tPMP-1-susceptible cells.

Animals↗

Influence of in vitro susceptibility phenotype against thrombin-induced platelet microbicidal protein on treatment and prophylaxis outcomes of experimental Staphylococcus aureus endocarditis.

Thrombin-induced platelet microbicidal protein-1 (tPMP-1) is a small, cationic staphylocidal peptide from rabbit platelets. In the current study, the outcomes of vancomycin treatment and prophylaxis were compared in experimental infective endocarditis (IE) caused by an isogenic Staphylococcus aureus strain pair differing in tPMP-1 susceptibility (tPMPS) or resistance (tPMPR) in vitro (ISP479C and ISP479R, respectively). Vancomycin therapy (selected for its intrinsically slow bactericidal activity) reduced ISP479C (but not ISP479R) densities in vegetations compared with controls (P<.01). In contrast, prophylactic administration of vancomycin yielded no differences in efficacies for the 2 challenge strains. These data suggest that the tPMPR phenotype in vitro has a negative effect on the antimicrobial therapy (but not the prophylaxis) of experimental S. aureus IE. These disparate results may be explained in part by the requirement for microbicidal effects in the treatment of established IE, whereas prophylactic efficacy depends more on growth inhibitory and antiadhesion effects.

Animals↗

In vitro resistance to thrombin-induced platelet microbicidal protein is associated with enhanced progression and hematogenous dissemination in experimental Staphylococcus aureus infective endocarditis.

We examined the influence of thrombin-induced platelet microbicidal protein 1 (tPMP-1) on the progression and hematogenous dissemination of experimental endocarditis caused by isogenic Staphylococcus aureus strains differing in tPMP susceptibility (tPMPs) or resistance (tPMPr) in vitro. Following simultaneous challenge of animals with both strains, significantly higher tPMPr bacterial densities were present in vegetations (P < 0.0001), kidneys (P < 0. 0001), and spleens (P < 0.0001) compared with those for the tPMPs strain. These data indicate that tPMP-1 limits the intravegetation proliferation and hematogenous dissemination of a tPMPs strain in experimental endocarditis, while the tPMPr phenotype confers a selective advantage associated with the enhanced progression of this infection.

Animals↗

Vancomycin-resistant enterococcal colonization in nonhospitalized HIV-infected patients.

We studied fecal colonization with vancomycin-resistant enterococci (VRE) in 89 HIV-infected nonhospitalized patients ages 24 to 62 years, including 70 (79%) men (including 41 homosexual and 5 bisexual men) and 19 (21%) women. Of the 89 patients, 61 (69%) were black, 25 (28%) Hispanic, and 3 (3%) white; 53 (60%) had history of ongoing or recent antibacterial therapy with trimethoprim/sulfamethoxazole (29), clarithromycin (18), amoxicillin (7), ofloxacin (3), and metronidazole, doxycycline, dicloxacillin, and cephalexin (1 each). VRE were not isolated from any of the patients studied.

AIDS-Related Opportunistic Infections↗

Phenotypic resistance to thrombin-induced platelet microbicidal protein in vitro is correlated with enhanced virulence in experimental endocarditis due to Staphylococcus aureus.

Thrombin-induced platelet microbicidal protein (tPMP) is secreted by rabbit platelets following thrombin stimulation, and it kills common endovascular pathogens in vitro, including Staphylococcus aureus. Therefore, pathogens which exhibit tPMP resistance in vitro possess a potential survival advantage in vivo at sites of endovascular damage. We generated an isogenic S. aureus strain pair, differing in tPMP susceptibility, by transposon (Tn551) mutagenesis of a tPMP-susceptible (tPMPs) parental strain (ISP479) to derive a stably tPMP-resistant (tPMPr) strain, ISP479R. ISP479 and ISP479R were equivalent in vitro in the following phenotypes: biotyping, antiobiograms, platelet adherence and aggregation, growth kinetics, cell wall-associated protein A expression, and fibrinogen binding. Genotypic comparisons of chromosomal DNA of strains ISP479 and ISP479R following restriction endonuclease digestion revealed indistinguishable pulsed-field gel electrophoretic patterns. The genotype exhibited by strain ISP479R was linked to the tPMP-resistant phenotype, as it was transducible into the initially tPMP-susceptible parental strain, ISP479. Southern hybridization verified the presence of a single copy of Tn551 in the same chromosomal restriction site of both ISP479R and tPMPr transductants of ISP479. The correlation of in vitro tPMP susceptibility phenotypes with the ability to induce experimental endocarditis (a prototypical endovascular infection) was evaluated. Despite equivalent rates of endocarditis induction, animals infected with strain ISP479R achieved significantly higher vegetation bacterial densities over a 7-day post-challenge period than did animals infected with strain ISP479. These data suggest that tPMPr microbial strains have a selective advantage in experimental staphylococcal endocarditis. Furthermore, the major impact of tPMP resistance upon endocarditis pathogenesis appears to involve a postvalvular adherence event(s), most probably by facilitating bacterial proliferation within vegetations.

Animals↗

Campylobacter jejuni septicemia--epidemiology, clinical features and outcome.

In 33 cases of Campylobacter jejuni septicemia, the disease was more common at the extremes of age: infants made up a third of the reported cases while 24% of patients were older than 50 years. Fever was noted in more than 80% of patients and chills in about a fourth. Enteritis was present in 70% of cases, and the gastrointestinal tract was the principal source of septicemia. Half of the patients did not have significant underlying disease but were at extremes of age, which may reflect relative host impairment. Mortality (25%) owing to C jejuni septicemia occurs mostly in compromised hosts.

Age Factors↗

Cefmenoxime therapy for gynecologic and obstetric infections.

Cefmenoxime, a new third-generation cephalosporin, was used as a single drug in the therapy for female genital tract infections. Therapeutic response was considered satisfactory in 21 of 22 cases of pelvic inflammatory disease, six of nine tuboovarian abscesses, two of three severe wound infections, and all five cases of endometritis. Overall, 34 of 39 patients responded. The peak serum antibiotic levels in this study ranged from 15.8 to 64 (average 48.7) micrograms/mL, and the trough level ranged from 0.9 to 4 (average 3.1) micrograms/mL. Cefmenoxime was tested in vitro against 424 isolates of anaerobes including 208 strains of bacteroides of which 80 were Bacteroides fragilis. Cefmenoxime inhibited the growth of 90% or greater of the organisms (minimal inhibitory concentration 90) at less than or equal to 64 micrograms/mL. The minimal inhibitory concentration for 75% of B fragilis was 32 micrograms/mL. This study suggests that cefmenoxime as a single-drug therapy is effective in the treatment of female genital tract infections caused by aerobic (including the gonococcus) and anaerobic bacteria.

Abscess↗

Newer beta-lactam antibiotics in the treatment of experimental Staphylococcus aureus endocarditis.

Antistaphylococcal activity of three beta-lactam antibiotics, i.e. cefmenoxime, cefotaxime and latamoxef (moxalactam) was compared with that of nafcillin by studying cure rates of aortic valvular endocarditis caused by one of three clinical isolates of Staphylococcus aureus in New Zealand white male rabbits. The animals were randomly allocated to a control and four antibiotic treatment groups. Each animal except the controls received 60 mg/kg of one antibiotic intramuscularly twice daily for two weeks, beginning 24 h after induction of endocarditis. The aortic valve was sterilized in 11 of 15 (73%) animals treated with cefmenoxime, nine of 13 (69%) treated with cefotaxime, 11 of 13 (85%) treated with latamoxef and 12 of 15 (80%) treated with nafcillin. All nine animals in the control group developed aortic valvular vegetations with an average of 2.4 X 10(9) cfu/g. The differences in sterility rates resulting from treatment with the four antibiotics were not statistically significant (P greater than 0.70).

Animals↗

In vitro activity of cefmenoxime, cefotaxime, latamoxef, cefazolin, nafcillin and vancomycin against 53 endocarditis and bacteremic strains of Staphylococcus aureus.

Antistaphylococcal activity of newer beta-lactam antibiotics, cefmenoxime, cefotaxime and latamoxef was compared with that of the more conventional antistaphylococcal agents, nafcillin, cefazolin and vancomycin. 53 strains of Staphylococcus aureus, 40 from patients with endocarditis and 13 from patients with bacteremia from other causes were tested in vitro against each antibiotic using agar dilution methods. Minimal concentration of antibiotic to inhibit 90% of strains tested was 2 micrograms/ml for cefmenoxime and cefotaxime, 8 micrograms/ml for latamoxef and only 0.5 microgram/ml for nafcillin, cefazolin and vancomycin. The newer beta-lactam antibiotics may not be preferred to nafcillin, cefazolin or vancomycin in the treatment of serious staphylococcal infections.

Anti-Bacterial Agents↗

In vitro activity of pipecolic acid amide of clindamycin (U-57930E) on anaerobic bacteria compared with those of clindamycin, cefoxitin, and chloramphenicol.

In vitro activity of pipecolic acid amide of clindamycin (U-57930E) against 265 isolates of anaerobic bacteria, including 66 strains of Bacteroides fragilis, was compared with those of clindamycin, chloramphenicol, and cefoxitin. At therapeutically achievable concentrations, the activities of all four antibiotics against anaerobic bacteria were similar.

Bacteria, Anaerobic↗

Chemoprophylaxis of anaerobic pulmonary infections. An experimental study in rabbits.

Chemoprophylaxis of anaerobic pulmonary infection due to aspiration was studied in a rabbit model with the view of comparing the efficacy of procaine penicillin, clindamycin, chloramphenicol, doxycycline and cefoxitin. The antibiotic treatment was commenced immediately following transtracheal inoculation of a mixture of Bacteroides fragilis, Streptococcus morbillorum, Fusobacterium nucleatum and Eubacterium lentum. Treatment was stopped after 48 h and lungs were examined for evidence of infection on the 10th day. Only clindamycin and carbencillin were highly efficacious in chemoprophylaxis and both drugs prevented pulmonary infection in 7 of 8 (87%) of the animals tested.

Anaerobiosis↗

In vitro activity of BU-2313B against anaerobic bacteria.

The antimicrobial efficacy of BU-2313B, a new antibiotic, was evaluated in comparison with clindamycin, chloramphenicol and cefoxitin against 265 clinical anaerobic isolates. BU-2313B inhibited 88% of 66 isolates of Bacteroides fragilis tested at 2 micrograms/ml, whereas clindamycin, chloramphenicol and cefoxitin inhibited 98, 97 and 92% of them at 2, 8 and 16 micrograms/ml, respectively. BU-2313B was severalfold more effective than chloramphenicol and cefoxitin, but it was eight times less effective than clindamycin.

Aminoglycosides↗

Rapid differentiation of bacterial meningitides by direct gas-liquid chromatography.

Rapid identification of Haemophilus influenzae and other bacillary meningitides was attempted by gas-liquid chromatography (GLC) of the metabolic by-products in broth cultures and in cerebrospinal fluid (CSF) samples obtained from experimental meningitis produced in New Zealand White male rabbits. These results were correlated with the GLC of CSF of meningitis patients. A major peak with retention time of succinic acid was found in the broth cultures of all bacilli tested including H. influenzae, Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, Proteus mirabilis, Citrobacter freundii, Pseudomonas aeruginosa, and Listeria monocytogenes. Succinic acid was also found in the CSF of experimental meningitis and in the CSF of all patients with H. influenzae and Esch. coli meningitis. This peak was not detected in the blood samples of experimental animals. It was also absent in the broth cultures of all of the gram-positive and gram-negative cocci tested, such as Streptococcus pneumoniae and Neisseria meningitidis. Succinic acid, which appears to be a by product of fermentation, persisted as a clear cut marker in H. influenzae meningitis for at least 3 d after the initiation of treatment. In one patient, the succinic acid peak disappeared during treatment and reappeared with a clinical relapse. Clearly, the presence of succinic acid that can be rapidly detected by GLC in the CSF excludes pneumococcal or meningococcal meningitis and strongly suggests H. influenzae or other bacillary meningitides.

Animals↗

Imaging endocarditis with Tc-99m-labeled antibody--an experimental study: concise communication.

The sensitivity and specificity of Tc-99m-labeled antibacterial antibody (Tc-99m Ab) for detecting bacterial endocarditis were evaluated in an experimental model. Rabbit-produced antistaphylococcal antibody was extracted using Rivanol and chemically labeled with Tc-99m. This Tc-99m Ab was injected intravenously in New Zealand rabbits 24 hr after producing Staphylococcus aureus endocarditis of the aortic valve. Imaging and tissue analyses were performed on the following day. All 11 animals developed S. aureus aortic-valve vegetations and showed increased uptake of Tc-99m Ab at the aortic valve, 118 times higher than at the uninfected tricuspid valve. Although high hepatic radioactivity and anatomic uncertainties interfered with in vivo delineation of these lesions, images of the excised hearts showed all affected valves. Two rabbits inoculated with Escherichia coli did not develop endocarditis and had little uptake of Tc-99m Ab, while six rabbits with enterococcal endocarditis had no uptake of the Tc-99m Ab in their vegetations. The findings suggest potential value of Tc-99m Ab on the rapid diagnosis of endocarditis.

Animals↗