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Biomedical subjects

M R Jacobs

Publications and source records attributed to M R Jacobs.

At least 181 records · Page 10Linked to original sources

Melaleuca oil poisoning.

A 23-month-old boy became confused and was unable to walk thirty minutes after ingesting less than 10 mL of T36-C7, a commercial product containing 100% melaleuca oil. The child was referred to a nearby hospital. His condition improved and he was asymptomatic within 5 hours of ingestion. He was discharged to home the following day. Melaleuca oil, extracted from the Melaleuca alternifolia, contains 50-60% terpenes and related alcohols. Clinical experience with products containing melaleuca oil is limited. This case report suggests that ingestion of a modest amount of a concentrated form of this oil may produce signs of toxicity.

Central Nervous System↗

Comparative activity of the new fluoroquinolone Bay y3118 against 177 penicillin susceptible and resistant pneumococci.

The activity of a new fluoroquinolone, Bay y3118, was evaluated in comparison to three quinolones (ciprofloxacin, ofloxacin, lomefloxacin) and four broad-spectrum oral cephalosporins (cefpodoxime, cefuroxime, cefaclor, cefixime) against 49 penicillin-susceptible pneumococci, 77 pneumococci with intermediate resistance and 51 penicillin-resistant pneumococci. Quinolone activity was not affected by the penicillin susceptibility status of the organisms. Bay y3118 was very active against all strains, with an MIC90 of 0.015 microgram/ml. Other quinolones were less active, with MIC90s of 4 micrograms/ml (ciprofloxacin and ofloxacin) and 8 micrograms/ml (lomefloxacin). Cephalosporin MICs rose parallel to those of penicillin. Cefuroxime and cefpodoxime were the most active cephalosporins, with MIC90s for strains showing susceptibility, intermediate resistance and resistance of 0.125-0.25, 2-4 and 4 micrograms/ml, respectively. Cefaclor and cefixime were less active, with corresponding MIC90s of 1-2, 8-16 and > 16 micrograms/ml, respectively.

Anti-Infective Agents↗

Corynebacterium striatum: a diphtheroid with pathogenic potential.

Although nondiphtherial corynebacteria are ubiquitous in nature and commonly colonize the skin and mucous membranes of humans, they rarely account for clinical infection. Corynebacterium striatum has rarely been reported to be a pathogen, causing pleuropulmonary infections and bacteremia in only immunocompromised or anatomically altered patients. We noted C. striatum to be the infecting pathogen or copathogen in six patients. To our knowledge, this report describes the first cases of C. striatum causing infection of exist sites of central venous catheters, thrombophlebitis associated with central venous catheters, conjunctivitis, and chorioamnionitis as well as a possible pathogen contributing to peritonitis and pyogenic granuloma. Unlike Corynebacterium jeikeium, which is highly resistant to beta-lactam agents, aminoglycosides, and quinolones, all strains of C. striatum isolated from the patients described in this report were susceptible to vancomycin and aminoglycosides, and all strains except one were susceptible to penicillin G, imipenem, and ciprofloxacin. C. striatum should be recognized as a potential pathogen in both immunocompromised and normal hosts in the appropriate circumstances, and appropriate antimicrobial therapy can quickly lead to resolution of infection.

Adult↗

Susceptibility of 170 penicillin-susceptible and penicillin-resistant pneumococci to six oral cephalosporins, four quinolones, desacetylcefotaxime, Ro 23-9424 and RP 67829.

MICs of six oral cephalosporins (cefdinir, cefpodoxime, cefaclor, cefuroxime, cefixime and Ro 40-6890), four quinolones (ciprofloxacin, ofloxacin, OPC-17116 and fleroxacin), desacetylcefotaxime, Ro 23-9424 (a fused combination of fleroxacin + desacetylcefotaxime) and RP 67829 (a benzonaphthyridine) were determined for 49 penicillin-susceptible (S), 38 penicillin-intermediate (I), and 83 penicillin-resistant (R) strains of Streptococcus pneumoniae. All MICs were determined by a standardized agar dilution method utilizing Mueller-Hinton agar supplemented with sheep blood. MIC90s of OPC-17116 and RP 67829 were < or = mg/L, and were unaffected by penicillin-susceptibility. MICs of all beta-lactams increased with increasing penicillin-MICs, with cefdinir, cefpodoxime, cefuroxime and Ro 40-6890 being the most active compounds, followed by cefaclor and cefixime. MIC90s of ciprofloxacin and ofloxacin were 2 mg/L. MIC90s of Ro 23-9424 were lower than those of either parent compound (fleroxacin 8 mg/mL for all three groups; desacetylcefotaxime 0.5 mg/mL [S], 0.5 mg/mL [I], 4 mg/mL [R]; Ro 23-9424 0.125 mg/L [S], 0.25 mg/L [I], 0.5 mg/L [R]). The results indicated that several newly introduced and experimental antimicrobials have potential for the treatment of infections caused by resistant strains of S. pneumoniae.

Anti-Infective Agents↗

Susceptibility of 539 gram-positive and gram-negative anaerobes to new agents, including RP59500, biapenem, trospectomycin and piperacillin/tazobactam.

Susceptibilities of 539 Gram-positive and Gram-negative anaerobes were tested by agar dilution against 15 new and existing antimicrobial agents. Organisms included 218 Bacteroides fragilis group strains, 15 non-fragilis group Bacteroides, 130 Porphyromonas/Prevotella, 49 fusobacteria, 50 peptostreptococci, 53 clostridia and 24 Gram-positive non-sporeforming bacilli. Of 412 Gram-negative bacilli, 89% were beta-lactamase-positive, while only two of the Gram-positive strains (both clostridia) produced this enzyme. Using established and preliminary breakpoints, all strains were susceptible to biapenem and imipenem (MIC90s 1 mg/L) and chloramphenicol (MIC90 8 mg/L). Only one of all the strains tested (a Cl. innocuum) was resistant (MIC > 4 mg/L) to RP59500; the latter had MIC90 2 mg/L, while 98% of strains were susceptible to trospectomycin (MIC90 16 mg/L). Ninety-nine per cent of strains were susceptible to piperacillin/tazobactam (MIC90 8 mg/L) compared to 86% to piperacillin (MIC90 > 64 mg/L). Corresponding data for ticarcillin/clavulanate versus ticarcillin were 97% susceptible (MIC90 8 mg/L) compared to 83% (MIC90 > 64 mg/L). Enhancement of the beta-lactam by the inhibitors was only seen in beta-lactamase-producing strains. Amoxycillin and cefoperazone were less often active (36% susceptible, MIC90 > 256 mg/L and 66% susceptible, MIC90 64 mg/L, respectively). Cefoxitin had greater activity than cefotetan (90% susceptible, MIC90 32 mg/L, compared to 72% susceptible, MIC90 > 64 mg/L). Metronidazole was active against 94% of strains (MIC90 4 mg/L). All metronidazole-resistant strains were Gram-positive (75% of non-sporeforming bacilli, 9% of clostridia and 6% of peptostreptococci). Ninety per cent of strains were susceptible to clindamycin (MIC90 4 mg/L).

Anti-Bacterial Agents↗

Health care research in rheumatology.

In the first three sections of this review, studies of disability among patients with musculoskeletal conditions are discussed. Evidence continues to demonstrate that arthritis has a substantial impact on disability. Correlates of disability for patients with general musculoskeletal conditions, rheumatoid arthritis, and osteoarthritis are reviewed, as are strategies to ameliorate arthritis-related disability. The fourth section of this review highlights the importance of pain-coping strategies for arthritis patients. The concluding section reviews educational strategies in the rheumatic diseases.

Adult↗

Susceptibilities of 428 gram-positive and -negative anaerobic bacteria to Bay y3118 compared with their susceptibilities to ciprofloxacin, clindamycin, metronidazole, piperacillin, piperacillin-tazobactam, and cefoxitin.

The susceptibilities of 428 gram-negative and gram-positive anaerobes (including selected cefoxitin-resistant strains) to Bay y3118 (a new fluoroquinolone), ciprofloxacin, clindamycin, metronidazole, cefoxitin, piperacillin, and piperacillin-tazobactam were tested. Organisms comprised 115 Bacteroides fragilis group, 116 non-B. fragilis Bacteroides, Prevotella, and Porphyromonas spp., 40 fusobacteria, 58 peptostreptococci, 48 gram-positive non-spore-forming rods, and 51 clostridia. beta-Lactamase production was demonstrated in 87% of the gram-negative rods but in none of the gram-positive organisms. Overall, Bay y3118 was the most active agent, with all organisms inhibited at an MIC of < or = 2.0 micrograms/ml (MICs for 50% [MIC50] and 90% [MIC90] of strains tested, 0.125 and 0.5 microgram/ml, respectively). By contrast, ciprofloxacin was much less active, with only 42% of strains susceptible at a breakpoint of 2.0 micrograms/ml (MIC50, 4.0 micrograms/ml; MIC90, 16.0 micrograms/ml). Metronidazole was active against all gram-negative rods, but 7% of peptostreptococci, 83% of gram-positive non-spore-forming rods, and 4% of non-Clostridium perfringens, non-Clostridium difficile clostridia were resistant to this agent (MICs, > 16.0 micrograms/ml). Clindamycin was active against 94% of Bacteroides, Prevotella, and Porphyromonas spp., 91% of peptostreptococci, and 100% of gram-positive non-spore-forming rods, but was active against only 70% of fusobacteria and 53% of clostridia. Cefoxitin was active against > or = 90% of all groups except the B. fragilis group and non-Propionibacterium acnes gram-positive non-spore-forming rods (both 85%) and C. difficile (20%). Significant enhancement of piperacillin by tazobactam was seen in all beta-lactamase-positive strains (99% susceptible; MIC90, 8.0 micrograms/ml), and all beta-lactamase-negative strains were susceptible to piperacillin (MIC90, 8.0 micrograms/ml). Clinical studies are required to delineate the role of Bay y3118 in the treatment of anaerobic infections.

Anti-Infective Agents↗

Anti-Mycobacterium avium activity of quinolones: in vitro activities.

The MICs of 88 quinolones against 14 selected reference and clinical strains of Mycobacterium avium-M. intracellular complex were determined. Agents tested included ciprofloxacin, sparfloxacin (PD 131501), and 86 other experimental quinolones. Test strains were selected to represent various susceptibilities to ciprofloxacin and other drug resistance profiles. MICs were determined by the microdilution method in 7HSF broth, with incubation for 14 days at 35 degrees C. The results showed 25 of the quinolones to be active against the strains, with MICs for 90% of the strains (MIC90s) of 2 to 32 micrograms/ml. Ten of these compounds had activities equivalent to or greater than that of ciprofloxacin. The most active compound was PD 125354, with an MIC50 of 0.5 micrograms/ml and an MIC90 of 2 micrograms/ml; comparable values for ciprofloxacin were 4 and 8 micrograms/ml, respectively. The next most active compounds, with MIC90s of 4 micrograms/ml, were sparfloxacin (PD 131501), PD 123982, PD 135144, and PD 119421. MIC90s of PD 131575, PD 126889, PD 122642, PD 139586, and PD 143289 were 8 micrograms/ml. Further evaluation of the most active agents is warranted, as is assessment of structure-activity relationships of active and inactive agents to elucidate the active portions of the compounds and to lead to the development of compounds with enhanced activity.

Anti-Infective Agents↗

Anti-Mycobacterium avium activity of quinolones: structure-activity relationship studies.

The structures and inhibitory activities of 88 quinolones, previously studied as potential in vitro inhibitors of 14 selected strains of Mycobacterium avium complex, were examined in an effort to identify a quinolone with optimal activity towards all strains. A MULTICASE structure-activity relationship analysis of the inhibitory activities of these 88 quinolones against 14 strains of M. avium was performed and led to the identification of a number of structural constraints required to overcome the resistance of most of the strains. Our data suggested that the increased resistance of the strains was probably not due to a specific resistance mechanism but rather due to gradual limitation of the constraints imposed on the structure of the quinolones. This increasing structural selectivity could be produced either at the level of cell membrane penetration or at the level of interaction with the DNA gyrase receptor site. On the basis of these findings, a number of new quinolones holding the promise of superior activity are currently being evaluated in vitro and in vivo to determine the clinical relevance of our observations.

4-Quinolones↗

Antimicrobial activity and in vitro corneal epithelial toxicity of antimicrobial agents for gram-positive corneal pathogens.

We assessed in vitro the antimicrobial activity of four agents (vancomycin, teicoplanin, mupirocin, and imipenem) which are effective against Gram-positive cocci causally associated with bacterial keratitis, as well as their corneal epithelial cytotoxicity. Minimal inhibitory concentrations inhibiting 90% of strains (MIC90s) against 10 strains each of methicillin-susceptible and -resistant Staphylococcus aureus and Staphylococcus epidermidis, penicillin-susceptible and -resistant Streptococcus pneumoniae, and viridans group streptococci were as follows: vancomycin (MIC90s 0.25-2 micrograms/ml), teicoplanin (MIC90s 0.25-4 micrograms/ml, mupirocin (MIC90s 0.12-4 micrograms/ml), and imipenem (MIC90s 0.008-0.25 micrograms/ml, except for methicillin-resistant staphylococci with MIC90 of 16 micrograms/ml). Cytotoxicity was assayed by uptake of 3H-thymidine by rabbit corneal epithelial cell cultures at drug concentrations of 12.5-100 mg/ml for vancomycin and teicoplanin, 1-8 mg/ml for mupirocin and 0.125-8 mg/ml for imipenem, with exposure times of 5, 30 and 60 min. Cytotoxicity was as follows: imipenem < mupirocin < vancomycin < or = teicoplanin. Resistance to methicillin-resistant S. aureus and S. epidermidis for imipenem and resistance to S. epidermidis and cytotoxicity for teicoplanin limit their consideration for suspected Gram-positive keratitis. On the other hand, vancomycin and mupirocin, because of their excellent therapeutic indices, should be considered for this indication.

Animals↗

Increase in TCR gamma delta T lymphocytes in synovia from rheumatoid arthritis patients with active synovitis.

To determine the relative presence of TCR gamma delta+ and TCR alpha beta+ T cells in synovial tissue from patients with various types of inflammatory synovitis and in tissues from patients with a number of chronic T cell-mediated conditions, we stained frozen tissue sections with monoclonal antibodies in indirect immunofluorescence assays. In tissues obtained from patients with chronic T cell-mediated granulomatous conditions (Wegener's granulomatosis, lymphomatoid granulomatosis, granuloma annulare, Langerhans' cells granulomatosis, pigmented villonodular synovitis, Takayasu's arteritis, and talc granulomatosis), the T cells present were predominantly TCR alpha beta+, without an increased presence of TCR gamma delta+ cells. In contrast, 6 of 14 (43%) synovia from patients with rheumatoid arthritis (RA) showed increased TCR gamma delta+ T cells (3-10 cells/hpf). The RA synovia with increased TCR gamma delta+ cells present had an increased tissue inflammation score compared to RA synovia with few TCR gamma delta+ cells [18.6 +/- 5.8 versus 11.6 +/- 4.2 (mean +/- SE), P less than 0.05]. In contrast, synovia from patients with osteoarthritis, systemic lupus erythematosus, and trauma did not show an increased presence of TCR gamma delta+ T cells. Thus, in cellular inflammatory infiltrates the presence of increased TCR gamma delta cells is not a component of noninfectious granulomatous inflammation but is found in approximately 40% of RA synovia with high levels of inflammation.

Adult↗

beta-Lactamase production and susceptibility of US and European anaerobic gram-negative bacilli to beta-lactams and other agents.

The susceptibility of 1,476 US and European strains of anaerobic gram-negative bacilli to amoxicillin, amoxicillin/clavulanate, ticarcillin, ticarcillin/clavulanate, cefoxitin, imipenem and metronidazole was determined. All of the Bacteroides fragilis group and 51% of the non-Bacteroides fragilis group were beta-lactamase positive. Amongst the non-Bacteroides fragilis group, beta-lactamase positivity rates were higher for US strains (58%) than for European strains (39%). All strains were susceptible to imipenem and metronidazole. MIC90s of amoxicillin and ticarcillin for all beta-lactamase negative strains were 0.5 and 2 micrograms/ml, respectively. The addition of clavulanate reduced the MIC90s of amoxicillin (> or = 256 micrograms/ml) and ticarcillin (> or = 64 micrograms/ml) to 16 and 8 micrograms/ml, respectively, for the Bacteroides fragilis group, and to 4 micrograms/ml for both agents for the non-Bacteroides fragilis beta-lactamase producing group. Twenty-nine cefoxitin-resistant strains were found, mainly in the Bacteroides fragilis group, while 95 beta-lactamase producing strains (predominantly Bacteroides fragilis group and fusobacteria) did not show synergy between beta-lactams and clavulanate. Of the newe agents tested, meropenem and piperacillin-tazobactam were the most active (100% of strains susceptible), followed by amoxicillin-BRL 42715 (99% of strains susceptible); 94 to 98% of the strains were susceptible to cefoperazone-sulbactam, tosufloxacin, temafloxacin and clindamycin. Only 73% of the strains were susceptible to cefotetan, compared to 91% to cefoxitin; 88% of the strains were susceptible to trospectomycin. Overall, all of the beta-lactam/beta-lactamase inhibitor combinations, imipenem, meropenem, cefoxitin, tosufloxacin, temafloxacin and clindamycin had good activity against beta-lactamase producing strains, while all agents tested had good activity against beta-lactamase negative strains.

Anti-Bacterial Agents↗

Evaluation of the E-Test for susceptibility testing of pneumococci.

The E-Test (AB Biodisk, Sweden) is an antibiotic gradient strip that is applied to an inoculated agar plate and results in an elliptical zone of inhibition that intercepts the graded strip, producing a quantitative (microgram per milliliter) result. Pneumococci (100) were used in this study, 38 penicillin-susceptible [minimal inhibitory concentrations (MICs), less than or equal to 0.12 micrograms/ml], 42 intermediately resistant (MICs, 0.12-1.0 micrograms/ml), and 20 resistant (MICs, greater than 1 microgram/ml). E-Test strips were evaluated on Mueller-Hinton agar plates with 5% sheep blood. Agar dilution MICs were determined by the National Committee for Clinical Laboratory Standards (NCCLS) method. Penicillin MICs for the E-Test tended to be slightly lower (one log2 dilution) than reference MICs due to the continuous scale from which E-Test MICs were read. All but two penicillin-susceptible isolates were correctly categorized by the E-Test method. Of the 62 penicillin-resistant strains, 59 had E-Test MICs of greater than or equal to 0.12 micrograms/ml, with 88% of these strains having E-Test MICs within one doubling dilution of the reference MICs. However, using the current NCCLS breakpoint MICs, many of the penicillin-resistant strains with reference MICs of 2 micrograms/ml were categorized as intermediate by the E-Test, with MICs of 0.38-1 microgram/ml. For chloramphenicol, erythromycin, and tetracycline, correlation of the two methods was excellent. E-Test chloramphenicol MICs provided clearer separation of susceptible and resistant strains than did the reference method. We conclude that the E-Test is a reliable method for determination of MICs of the antibiotics evaluated for pneumococci.

Chloramphenicol↗

Treatment and diagnosis of infections caused by drug-resistant Streptococcus pneumoniae.

Drug-resistant strains of Streptococcus pneumoniae have now been reported from all continents and have become the predominant pathogens in some areas; many strains are resistant to multiple agents. Because of the importance of pneumococci in the etiology of meningitis, the criteria used to assess susceptibility are conservative: strains with minimal inhibitory concentrations (MICs) of penicillin G of less than or equal to 0.06 microgram/mL are regarded as susceptible, those with MICs of 0.1-1 microgram/mL are considered intermediately resistant, and those with MICs of greater than 1 microgram/mL are designated highly resistant. The diagnosis, treatment, and prevention of infections due to resistant pneumococci are the subjects of this review. Methods of susceptibility testing have now been well defined for pneumococci. Screening for penicillin resistance with 1-microgram oxacillin disks is recommended for all clinically significant isolates. The activity of other beta-lactam agents against penicillin-resistant strains has been documented, and the MICs of a number of non-beta-lactam agents have been determined as well. Treatment of resistant pneumococcal infections depends on the site of infection, the degree of resistance to penicillin G, the resistance of the infecting strain to other agents, the severity of disease, the presence of underlying conditions, and the dose and route of administration of antimicrobial agents. Current recommendations for treatment are based on retrospective case studies, and adequate prospective studies providing more definitive data are needed. Prevention of pneumococcal infections in children less than 2 years of age and in the elderly remains a problem. Improved vaccines must be developed for this purpose.

Carrier State↗

Prevalence and characteristics of pharyngeal group A beta-hemolytic streptococci in US Navy recruits receiving benzathine penicillin prophylaxis.

US military recruits receive benzathine penicillin prophylaxis because of endemicity of group A beta-hemolytic streptococcal (GABHS) infections. GABHS prevalence in Navy recruits receiving single-dose benzathine penicillin prophylaxis was assessed during spring and fall 1989 by culturing throat specimens from randomly selected groups of approximately 230 men before and 2, 4, and 7 weeks after prophylaxis and from men with pharyngitis diagnosed at sick call. Of 60 GABHS isolates, 75% were serotype M-3. The pharyngitis rate increased from 0.18% in the spring to 1.55% in the fall with a concurrent increase in serotype M-3 prevalence from 35% to 91%. The GABHS prevalence rate was three- to fourfold lower after prophylaxis. There were no cases of acute rheumatic fever (ARF) despite predominance of M-3, a rheumatogenic serotype. It was concluded that penicillin prophylaxis continues to be effective for control of GABHS infections and prevention of ARF in Navy recruits.

Drug Hypersensitivity↗

Susceptibilities of penicillin-susceptible and -resistant strains of Streptococcus pneumoniae to RP 59500, vancomycin, erythromycin, PD 131628, sparfloxacin, temafloxacin, win 57273, ofloxacin, and ciprofloxacin.

The MICs of four new quinolones, sparfloxacin (AT-4140, CI-978), PD 131628 (the active form of the prodrug CI-990), temafloxacin, and Win 57273, compared with those of ciprofloxacin and ofloxacin were tested against 53 penicillin-susceptible, 35 penicillin intermediate-resistant, and 51 penicillin-resistant pneumococci. Susceptibility to RP 59500, a new streptogramin, was also tested and compared with those to the quinolones, erythromycin, and vancomycin. All MICs were determined by a standardized agar dilution method by using Mueller-Hinton agar supplemented with sheep blood. Quinolone, vancomycin, and RP 59500 susceptibilities were not affected by susceptibility or resistance to penicillin. For Win 57273, the MICs for 50% (MIC50) and 90% (MIC90) of strains tested were 0.015 and 0.03 micrograms/ml, respectively. MIC50S of both sparfloxacin and PD 131628 were 0.25 micrograms/ml, and MIC90S were 0.5 micrograms/ml. The MIC50 of temafloxacin was 0.5 micrograms/ml, and the MIC90 was 1.0 micrograms/ml. By comparison, ofloxacin and ciprofloxacin both yielded MIC50S of 1.0 micrograms/ml and MIC90s of 2.0 micrograms/ml. RP 59500 yielded an MIC50 of 0.5 microgram/ml and an MIC90 of 1.0 microgram/ml and was only 1 doubling dilution less active against 17 erythromycin-resistant strains. Vancomycin was active against all strains (MIC50, 0.25 microgram/ml; MIC90, 0.5 microgram/ml). All four experimental quinolones as well as RP 59500 show promise for therapy of infections with penicillin-resistant and -susceptible pneumococci.

Anti-Infective Agents↗