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M R Jacobs

Publications and source records attributed to M R Jacobs.

At least 91 records · Page 5Linked to original sources
PubMed1999

Activity of quinolones against mycobacteria.

The fluoroquinolones have been shown to be active in vitro against many mycobacterial species, including most strains of Mycobacterium tuberculosis complex and M. fortuitum, and some strains of M. kansasii, M. avium-intracellulare (MAI) complex and M. leprae. Ciprofloxacin, ofloxacin and sparfloxacin are the best studied of these agents to date, and are among the most active of this group against M. tuberculosis and other mycobacteria. Treatment of patients with multidrug-resistant pulmonary tuberculosis using ofloxacin has resulted in the selection of quinolone-resistant mutants in a few patients. Many strains of MAI, however, are resistant to fluoroquinolones, and structure-activity relationships and DNA gyrase studies have been undertaken to identify the moieties associated with activity and the lack thereof. The genetic and molecular basis of quinolone resistance in mycobacteria has revealed both the recent progress made in these areas and the limitations of the quinolones against this genus. Considerable progress will need to be made in resolving these issues in order for the quinolones to become clinically useful antimycobacterial agents.

4-Quinolones↗
PubMed1999

Emergence of antibiotic resistance in upper and lower respiratory tract infections.

The increase in antibiotic resistance is of great concern to the medical community. The treatment of respiratory tract infections are significantly impacted by resistance, as 67% of antibiotic use in adults and 87% in children is for the treatment of such infections. The most common pathogens implicated in these infections are Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis, and isolates of all 3 have developed resistance to some of the antibiotics currently on the market. In 1997, one third of S. pneumoniae strains were classified as penicillin resistant, up to 50% of H. influenzae strains produced beta-lactamase, and all M. catarrhalis strains produced beta-lactamase. As resistance can vary with geographic region and specific populations, one way to determine the-most effective antibiotic for an infection is to ascertain the resistance pattern of these pathogens from local laboratories or national surveillance studies. Breakpoints using pharmacodynamic data based on drug concentration present for at least 40% of the dosing interval, or area under the serum concentration curve:minimum inhibitory concentration ratios have been valuable for comparing the activities of oral agents. Of the currently available beta-lactams and macrolides, only amoxicillin/clavulanate and daily intramuscular ceftriaxone are active against more than 90% of all 3 respiratory pathogens. Newer quinolones are also active against these pathogens, but overuse is very likely to result in rapid development of resistance, and their use should be reserved for patients with treatment failure or significant drug allergies.

Adult↗
PubMed1999

Acute otitis media: management and surveillance in an era of pneumococcal resistance--a report from the Drug-resistant Streptococcus pneumoniae Therapeutic Working Group.

OBJECTIVE: To provide recommendations [corrected] for the management of acute otitis media (AOM) and the surveillance of drug-resistant Streptococcus pneumoniae (DRSP). Five questions were addressed: (1) Can amoxicillin remain the best initial antimicrobial agent for treating AOM in the current period of increasing prevalence of DRSP? (2) What are suitable alternative agents for use if amoxicillin fails? (3) Should empiric treatment of AOM vary by geographic region? (4) Where can clinicians learn about resistance patterns in their patient populations? (5) What modifications to laboratory surveillance would improve the utility of the information for clinicians treating AOM? PARTICIPANTS: Experts in the management of otitis media and the DRSP Therapeutic Working Group. This group was convened by the CDC to respond to changes in antimicrobial susceptibility among pneumococci and includes clinicians, academicians and public health practitioners. EVIDENCE: Published and unpublished data summarized from the scientific literature and experience from the experts present. PROCESS: [corrected] After group presentations and review of background materials, subgroup chairs prepared draft responses to the five questions, discussed the responses as a group and edited those responses [corrected]. CONCLUSIONS: Oral amoxicillin should remain the first line antimicrobial agent for treating AOM. In view of the increasing prevalence of DRSP, the safety of amoxicillin at higher than standard dosages and evidence that higher dosages of amoxicillin can achieve effective middle ear fluid concentrations, an increase in the dosage used for empiric treatment from 40 to 45 mg/kg/day to 80 to 90 mg/kg/day is recommended. For patients with clinically defined treatment failure after 3 days of therapy, useful alternative agents include oral amoxicillin-clavulanate, cefuroxime axetil and intramuscular ceftriaxone. Many of the 13 other Food and Drug Administration-approved otitis media drugs lack good evidence for efficacy against DRSP. Currently local surveillance data for pneumococcal resistance that are relevant for the clinical management of AOM are not available from most areas in the United States. Recommendations to improve surveillance include establishing criteria for setting susceptibility breakpoints for clinically appropriate antimicrobials to ensure relevance for treating AOM, testing middle ear fluid or nasal swab isolates in addition to sterile site isolates and testing of drugs that are useful in treating AOM. The management of otitis media has entered a new era with the development of DRSP. These recommendations are intended to provide a framework for appropriate clinical and public health responses to this problem.

Acute Disease↗
PubMed1998

A phase II/III trial of antimicrobial therapy with or without amikacin in the treatment of disseminated Mycobacterium avium infection in HIV-infected individuals. AIDS Clinical Trials Group Protocol 135 Study Team.

OBJECTIVE: To determine the clinical and microbiologic benefit of adding amikacin to a four-drug oral regimen for treatment of disseminated Mycobacterium avium infection in HIV-infected patients. DESIGN: A randomized, open-labeled, comparative trial. SETTING: Outpatient clinics. PATIENTS: Seventy-four patients with HIV and symptomatic bacteremic M. avium infection. INTERVENTIONS: Rifampin 10 mg/kg daily, ciprofloxacin 500 mg twice daily, clofazimine 100 mg every day, and ethambutol 15 mg/kg orally daily for 24 weeks, with or without amikacin 10 mg/kg intravenously or intramuscularly 5 days weekly for the first 4 weeks. MAIN OUTCOME MEASURE: Clinical and microbiologic response at 4 weeks; quantitative level of bacteremia with M. avium. RESULTS: No difference in clinical response was noted with the addition of amikacin to the four-drug oral regimen, and only 25% in either group had a complete or partial response at 4 weeks. A comparable quantitative decrease in bacteremia was noted in both treatment groups, with 16% of patients being culture-negative at 4 weeks and 38% at 12 weeks. Toxicities were mainly gastrointestinal. Amikacin was well tolerated. Median survival was 30 weeks in both groups. CONCLUSIONS: The addition of amikacin to a four-drug oral regimen of rifampin, ciprofloxacin, clofazimine, and ethambutol did not provide clinical or microbiologic benefit.

AIDS-Related Opportunistic Infections↗
PubMed1998

Synergistic activity of trovafloxacin with other agents against gram-positive and -negative organisms.

The synergistic activity of trovafloxacin with other agents against 55 Gram-positive and -negative bacteria was determined by checkerboard titration. Synergistic fractional inhibitory concentration (FIC) indices (< or = 0.5) were seen in two methicillin-susceptible and one methicillin-resistant Staphyloccocus aureus with teicoplanin, one of each of the latter two with vancomycin; one methicillin-resistant coagulase-negative Staphylococcus with rifampin and one with fusidic acid; five Stenotrophomonas maltophilia with cefoperazone; three Pseudomonas aeruginosa with ticarcillin/clavulanate, four with aztreonam, two with ceftazidime, one with tobramycin, one with cefoperazone, and one with ceftriaxone; one pneumococcus with ceftriaxone; one Enterococcus faecalis with ceftriaxone, and one with vancomycin; two Bacteroides fragilis with metronidazole, two with clindamycin, and one with cefoxitin; and one Clostridium perfringens with metronidazole and one with clindamycin. All other FIC indices were additive/indifferent (0.51-2.0), and no antagonistic FIC indices (> 4.0) were observed.

Anti-Infective Agents↗
PubMed1998

Anti-anaerobic activity of erythromycin, azithromycin and clarithromycin: effect of pH adjustment of media to compensate for pH shift caused by incubation in CO2.

The activity of erythromycin, azithromycin and clarithromycin against 112 anaerobes was tested by the Oxyrase agar dilution MIC method at pH 7.2 without supplemental CO2 and by an agar dilution MIC method in CO2 with media adjusted to pH 8.0. MICs (mg/L) of erythromycin, azithromycin and clarithomycin against Bacteroides fragilis ATCC 25285 and Bacteroides thetaiotaomicron ATCC 29741 were similar by the two methods. MICs for 94 clinical isolates tested by the two methods were within two dilutions of each other. Eighteen additional isolates required CO2, and did not grow in Oxyrase. With the exception of fusobacteria, with which azithromycin yielded the lowest MICs, clarithromycin had the lowest MICs with both methods. These results show that the pH effect of incubation in CO2 can be avoided by using the Oxyrase method, or by incubating in CO2 with pH adjusted to 8.0. The latter method has the advantage of allowing testing of strains requiring CO2.

Anti-Bacterial Agents↗
PubMed1998

In vitro selection of resistance to four beta-lactams and azithromycin in Streptococcus pneumoniae.

Selection of resistance to amoxicillin (with or without clavulanate), cefaclor, cefuroxime, and azithromycin among six penicillin G- and azithromycin-susceptible pneumococcal strains and among four strains with intermediate penicillin sensitivities (azithromycin MICs, 0.125 to 4 microg/ml) was studied by performing 50 sequential subcultures in medium with sub-MICs of these antimicrobial agents. For only one of the six penicillin-susceptible strains did subculturing in medium with amoxicillin (with or without clavulanate) lead to an increased MIC, with the MIC rising from 0.008 to 0.125 microg/ml. Five of the six penicillin-susceptible strains showed increased azithromycin MICs (0.5 to >256.0 microg/ml) after 17 to 45 subcultures. Subculturing in medium with cefaclor did not affect the cefaclor MICs of three strains but and led to increased cefaclor MICs (from 0.5 to 2.0 to 4.0 microg/ml) for three of the six strains, with MICs of other beta-lactams rising 1 to 3 twofold dilutions. Subculturing in cefuroxime led to increased cefuroxime MICs (from 0.03 to 0.06 microg/ml to 0.125 to 0.5 microg/ml) for all six strains without significantly altering the MICs of other beta-lactams, except for one strain, which developed an increased cefaclor MIC. Subculturing in azithromycin did not affect beta-lactam MICs. Subculturing of the four strains with decreased penicillin susceptibility in amoxicillin (with or without clavulanate) or cefuroxime did not select for beta-lactam resistance. Subculturing of one strain in cefaclor led to an increase in MIC from 0.5 to 2.0 microg/ml after 19 passages. In contrast to strains that were initially azithromycin susceptible, which required >10 subcultures for resistance selection, three of four strains with azithromycin MICs of 0.125 to 4.0 microg/ml showed increased MICs after 7 to 13 passages, with the MICs increasing to 16 to 32 microg/ml. All azithromycin-resistant strains were clarithromycin resistant. With the exception of strains that contained mefE at the onset, no strains that developed resistance to azithromycin contained ermB or mefE, genes that have been found in macrolide-resistant pneumococci obtained from clinic patients.

Anti-Bacterial Agents↗
PubMed1998

Postantibiotic effect and postantibiotic sub-MIC effect of quinupristin-dalfopristin against gram-positive and -negative organisms.

Quinupristin-dalfopristin produced postantibiotic effects (PAEs) and postantibiotic sub-MIC effects of >2 h against 18 gram-positive cocci. Mean pneumococcal and staphylococcal PAEs were 2.8 and 4.7 h, respectively, with shorter PAEs for constitutively than inducibly macrolide-resistant staphylococci. Mean PAEs for vancomycin-susceptible and -resistant Enterococcus faecium were 8.5 and 2.6 h, respectively.

Anti-Bacterial Agents↗
PubMed1998

Activity of HMR 3647 compared to those of five agents against Haemophilus influenzae and moraxella catarrhalis by MIC determination and time-kill assay.

The microdilution MICs of HMR 3647, erythromycin A, azithromycin, clarithromycin, roxithromycin, and pristinamycin against 50/90% of 249 Haemophilus influenzae and 50 Moraxella catarrhalis isolates were 2/4, 0.06/0.125; 8/16, 0.25/0.25; 2/4, 0.06/0.125; 16/16, 0.25/0.25; 32/>32, 1/2; and 2/4, 0.5/0.5 microg/ml. Azithromycin was bactericidal against all 10 H. influenzae and 3 of 5 M. catarrhalis isolates and HMR 3647, erythromycin A, clarithromycin, roxithromycin, and pristinamycin were bacteriostatic, against all 15 strains after 24 h at the MIC.

Anti-Bacterial Agents↗
PubMed1998

In vitro activities of cefminox against anaerobic bacteria compared with those of nine other compounds.

The agar dilution MIC method was used to test the activity of cefminox, a beta-lactamase-stable cephamycin, compared with those of cefoxitin, cefotetan, moxalactam, ceftizoxime, cefotiam, cefamandole, cefoperazone, clindamycin, and metronidazole against 357 anaerobes. Overall, cefminox was the most active beta-lactam, with an MIC at which 50% of isolates are inhibited (MIC50) of 1.0 microg/ml and an MIC90 of 16.0 microg/ml. Other beta-lactams were less active, with respective MIC50s and MIC90s of 2.0 and 64.0 microg/ml for cefoxitin, 2.0 and 128.0 microg/ml for cefotetan, 2.0 and 64.0 microg/ml for moxalactam, 4.0 and > 128.0 microg/ml for ceftizoxime, 16.0 and > 128.0 microg/ml for cefotiam, 8.0 and >128.0 microg/ml for cefamandole, and 4.0 and 128.0 microg/ml for cefoperazone. The clindamycin MIC50 and MIC90 were 0.5 and 8.0 microg/ml, respectively, and the metronidazole MIC50 and MIC90 were 1.0 and 4.0 microg/ml, respectively. Cefminox was especially active against Bacteroides fragilis (MIC90, 2.0 microg/ml), Bacteroides thetaiotaomicron (MIC90, 4.0 microg/ml), fusobacteria (MIC90, 1.0 microg/ml), peptostreptococci (MIC90, 2.0 microg/ml), and clostridia, including Clostridium difficile (MIC90, 2.0 microg/ml). Time-kill studies performed with six representative anaerobic species revealed that at the MIC all compounds except ceftizoxime were bactericidal (99.9% killing) against all strains after 48 h. At 24 h, only cefminox and cefoxitin at 4x the MIC and cefoperazone at 8x the MIC were bactericidal against all strains. After 12 h, at the MIC all compounds except moxalactam, ceftizoxime, cefotiam, cefamandole, clindamycin, and metronidazole gave 90% killing of all strains. After 3 h, cefminox at 2 x the MIC produced the most rapid effect, with 90% killing of all strains.

Anti-Bacterial Agents↗
PubMed1998

Prevalence of antimicrobial-resistant pathogens in middle ear fluid: multinational study of 917 children with acute otitis media.

The management of acute otitis media is complicated by the emergence of resistance to beta-lactam and other antibiotics among common pathogens. We conducted a large, international study of infants and children with acute otitis media to identify pathogens and susceptibility patterns. During the winter of 1994 to 1995, middle ear fluid samples were collected from 917 patients with acute otitis media in Bulgaria, the Czech Republic, Hungary, Romania, Slovakia, Israel, and the United States. A single reference laboratory performed in vitro susceptibility testing. Pathogens were isolated from 62% of the patients. For Streptococcus pneumoniae (30% of the patients), untypeable Haemophilus influenzae (17%), and Moraxella catarrhalis (4%), there was significant variation among geographic regions (P < 0.001). The composite susceptibilities of these three organisms to amoxicillin ranged from 62% in the United States to 89% in Eastern and Central Europe; the corresponding susceptibilities to amoxicillin-clavulanate ranged from 90% in Israel to 95% in Eastern and Central Europe. beta-Lactamase was produced by 31 and 100% of the isolates of H. influenzae and M. catarrhalis, respectively. More isolates of S. pneumoniae were susceptible to amoxicillin (90%) or amoxicillin-clavulanate (90%) than to penicillin (70%; P = 0.002). The prevalence of resistant S. pneumoniae was highest in patients less than 12 months of age. S. pneumoniae, H. influenzae, and M. catarrhalis remain the most important bacterial pathogens in patients with acute otitis media; however, their prevalence is variable and resistance patterns are changing.

Acute Disease↗
PubMed1998

Susceptibilities of penicillin- and erythromycin-susceptible and -resistant pneumococci to HMR 3647 (RU 66647), a new ketolide, compared with susceptibilities to 17 other agents.

Susceptibility of 230 penicillin- and erythromycin-susceptible and -resistant pneumococci to HMR 3647 (RU 66647), a new ketolide, was tested by agar dilution, and results were compared with those of erythromycin, azithromycin, clarithromycin, roxithromycin, rokitamycin, clindamycin, pristinamycin, ciprofloxacin, sparfloxacin, trimethoprim-sulfamethoxazole, doxycycline, chloramphenicol, cefuroxime, ceftriaxone, imipenem, and vancomycin. HMR 3647 was very active against all strains tested, with MICs at which 90% of the strains were inhibited (MIC90s) of 0.03 microg/ml for erythromycin-susceptible strains (MICs, < or =0.25 microg/ml) and 0.25 microg/ml for erythromycin-resistant strains (MICs, > or =1.0 microg/ml). All other macrolides yielded MIC90s of 0.03 to 0.25 and >64.0 microg/ml for erythromycin-susceptible and -resistant strains, respectively. The MICs of clindamycin for 51 of 100 (51%) erythromycin-resistant strains were < or =0.125 microg/ml. The MICs of pristinamycin for all strains were < or =1.0 microg/ml. The MIC90s of ciprofloxacin and sparfloxacin were 4.0 and 0.5 microg/ml, respectively, and were unaffected by penicillin or erythromycin susceptibility. Vancomycin and imipenem inhibited all strains at < or =1.0 microg/ml. The MICs of cefuroxime and cefotaxime rose with those of penicillin G. The MICs of trimethoprim-sulfamethoxazole, doxycycline, and chloramphenicol were variable but were generally higher in penicillin- and erythromycin-resistant strains. HMR 3647 had the best kill kinetics of all macrolides tested against 11 erythromycin-susceptible and -resistant strains, with uniform bactericidal activity (99.9% killing) after 24 h at two times the MIC and 99% killing of all strains at two times the MIC after 12 h for all strains. Pristinamycin showed more rapid killing at 2 to 6 h, with 99.9% killing of 10 of 11 strains after 24 h at two times the MIC. Other macrolides showed significant activity, relative to the MIC, against erythromycin-susceptible strains only.

Anti-Bacterial Agents↗
PubMed1998

Activities and time-kill studies of selected penicillins, beta-lactamase inhibitor combinations, and glycopeptides against Enterococcus faecalis.

The activities of piperacillin, piperacillin-tazobactam, ticarcillin, ticarcillin-clavulanate, ampicillin, ampicillin-sulbactam, vancomycin, and teicoplanin were tested against 212 Enterococcus faecalis strains (9 beta-lactamase producers) by standard agar dilution MIC testing (10[4] CFU/spot). The MICs at which 50 and 90% of the isolates were inhibited (MIC50s and MIC90s, respectively) were as follows (microg/ml): piperacillin, 4 and 8; piperacillin-tazobactam, 4 and 8; ticarcillin, 64 and 128; ticarcillin-clavulanate, 64 and 128; ampicillin, 2 and 2; ampicillin-sulbactam, 1 and 2; vancomycin, 1 and 4; and teicoplanin, 0.5 and 1. Agar dilution MIC testing of the nine beta-lactamase-positive strains with an inoculum of 10(6) CFU/spot revealed higher beta-lactam MICs (piperacillin, 64 to >256 microg/ml; ticarcillin, 128 to >256 microg/ml; and ampicillin, 16 to 128 microg/ml); however, MICs with the addition of inhibitors were similar to those obtained with the lower inoculum. Time-kill studies of 15 strains showed that piperacillin-tazobactam was bactericidal (99.9% killing) for 14 strains after 24 h at four times the MIC, with 90% killing of all 15 strains at two times the MIC. After 12 and 6 h, 90% killing of 14 and 13 strains, respectively, was found at two times the MIC. Ampicillin gave 99.9% killing of 14 beta-lactamase-negative strains after 24 h at eight times the MIC, with 90% killing of all 15 strains at two times the MIC. After 12 and 6 h, 90% killing of 14 and 13 strains, respectively, was found at two times the MIC. Killing by ticarcillin-clavulanate was slower than that observed for piperacillin-tazobactam, relative to the MIC. For the one beta-lactamase-producing strain tested by time-kill analysis with a higher inoculum, addition of the three inhibitors (including sulbactam) to each of the beta-lactams resulted in bactericidal activity at 24 h at two times the MIC. For an enzyme-negative strain, addition of inhibitors did not influence kinetics. Kinetics of vancomycin and teicoplanin were significantly slower than those of the beta-lactams, with bactericidal activity against 6 strains after 24 h at eight times the MIC, with 90% killing of 12 and 14 strains, respectively, at four times the MIC. Slower-kill kinetics by both glycopeptides were observed at earlier periods.

Anti-Bacterial Agents↗
PubMed1998

Determination of activities of levofloxacin, alone and combined with gentamicin, ceftazidime, cefpirome, and meropenem, against 124 strains of Pseudomonas aeruginosa by checkerboard and time-kill methodology.

A total of 124 Pseudomonas aeruginosa strains were tested for synergy between levofloxacin and cefpirome, ceftazidime, gentamicin, and meropenem. Checkerboards yielded synergistic fractional inhibitory concentration (FIC) indices (< or =0.5) with 25 of 496 possible combinations. All other FIC indices were >0.5 to 2 (additive or indifferent), with no antagonism. Time-kill studies with 12 strains showed that levofloxacin (0.06 to 0.5 microg/ml) was synergistic with cefpirome, ceftazidime, gentamicin, and meropenem in 10, 9, 4, and 11 strains, respectively.

Anti-Bacterial Agents↗
PubMed1998

Postantibiotic effect and postantibiotic sub-MIC effect of levofloxacin compared to those of ofloxacin, ciprofloxacin, erythromycin, azithromycin, and clarithromycin against 20 pneumococci.

The postantibiotic effect (PAE) (10 times the MIC of quinolones, 5 times the MIC of macrolides) and postantibiotic sub-MIC effect (PAE-SME) at 0.125, 0.25, and 0.5 times the MIC were determined for levofloxacin, ciprofloxacin, ofloxacin, erythromycin, azithromycin, and clarithromycin against 20 pneumococci. Quinolone PAEs ranged between 0.5 and 6.5 h, and macrolide PAEs ranged between 1 and 6 h. Measurable PAE-SMEs (in hours) at the three concentrations were 1 to 5, 1 to 8, and 1 to 8, respectively, for quinolones and 1 to 8, 1 to 8, and 1 to 6, respectively, for macrolides.

Anti-Bacterial Agents↗
PubMed1998

Antipneumococcal activity of grepafloxacin compared to that of other agents by time-kill methodology.

Time-kill studies compared the activities of grepafloxacin with those of ciprofloxacin, levofloxacin, sparfloxacin, amoxicillin-clavulanate, and clarithromycin against 12 pneumococcal strains. Grepafloxacin was bactericidal after 24 h against all strains at a concentration of < or = 0.5 microg/ml, while sparfloxacin, levofloxacin, and ciprofloxacin were bactericidal at concentrations of < or = 1.0, < or = 2.0, and < or = 8.0 microg/ml, respectively. Amoxicillin-clavulanate and clarithromycin were bactericidal at 2x the MIC after 24 h against 12 of 12 strains and against all 8 macrolide-susceptible strains, respectively.

Anti-Bacterial Agents↗
PubMed1998

Comparative activities of clinafloxacin against gram-positive and -negative bacteria.

Activities of clinafloxacin, ciprofloxacin, levofloxacin, sparfloxacin, trovafloxacin, piperacillin, piperacillin-tazobactam, trimethoprim-sulfamethoxazole, ceftazidime, and imipenem against 354 ciprofloxacin-susceptible and -intermediate-resistant organisms were tested by agar dilution. Clinafloxacin yielded the lowest quinolone MICs (< or = 0.5 microg/ml against ciprofloxacin-susceptible organisms and < or = 16.0 microg/ml against ciprofloxacin-intermediate-resistant organisms) compared to those of levofloxacin, trovafloxacin, and sparfloxacin. Ceftazidime, piperacillin alone or combined with tazobactam, trimethoprim-sulfamethoxazole, and imipenem usually yielded higher MICs against ciprofloxacin-resistant strains.

Anti-Bacterial Agents↗