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M R Jacobs

Publications and source records attributed to M R Jacobs.

At least 19 recordsLinked to original sources
PubMed2002

Macrolide resistance phenotypes in Streptococcus pneumoniae in Santiago, Chile.

The mechanism of resistance was investigated in 39 macrolide-resistant clinical isolates of Streptococcus pneumoniae isolated from January 1997 to July 1999 in Santiago, Chile. Our results showed that 22 (56.5%) were macrolide-resistant, clindamycin-susceptible isolates (M phenotype) and 17 (43.5%) were macrolide and clindamycin resistant (MLS(B) phenotype). mefE gene was detected in all M phenotype, while ermB gene was detected in all MLS(B)-phenotype strains. Serotype 14 was the most frequent serotype among M-phenotype strains, and serotypes 19 and 23F were the most frequent serotypes in MLS(B) strains. These results demonstrate that both phenotypes of macrolide-resistant S. pneumoniae are found in Santiago, Chile, with the M phenotype predominating.

Adult↗
PubMed2002

Single- and multistep selection study of the antipneumococcal activity of BMS-284756 compared to ciprofloxacin, levofloxacin, trovafloxacin and moxifloxacin.

Single- and Multi-step selection studies were used to test the ability of BMS-284756, ciprofloxacin, levofloxacin, trovafloxacin and moxifloxacin to yield resistant clones from 12 quinolone-susceptible and -resistant Streptococcus pneumoniae strains. Although all quinolones selected, to a greater or lesser degree, for resistant clones with mutations usually in parC or gyrA, BMS-284756 tended to select for resistant clones at a lower rate than other quinolones studied.

Anti-Infective Agents↗
PubMed2001

Pneumococcal conjugate vaccine serotypes of Streptococcus pneumoniae isolates and the antimicrobial susceptibility of such isolates in children with otitis media.

The ability of the recently licensed 7-valent pneumococcal conjugate vaccine to cover isolates that cause otitis media, especially drug-resistant ones, was assessed using 500 recently obtained US isolates. Of these isolates, 418 (84%) belonged to vaccine-related serogroups, whereas 82 (16%) belonged to non-vaccine-related serogroups. Serotype 3 accounted for 48 (59%) of the non-vaccine-related serogroups. In addition, 93% of the isolates from patients < or =3 years of age belonged to serotypes that were included in or related to the heptavalent vaccine, compared with 49% of the isolates from older patients (P=.001). Most of the isolates (98%-100%) that were resistant to the antimicrobial agents tested were covered by the heptavalent vaccine, including 95.1% of the isolates from patients <2 years of age. The 7-valent pneumococcal conjugate vaccine could therefore potentially provide protection against all but 1 (type 3) of the common otitis media-associated pneumococcal serogroups identified in this study as well as against 98% of antibiotic-resistant isolates.

Adolescent↗
PubMed2001

Carriage of antibiotic-resistant pneumococci among Asian children: a multinational surveillance by the Asian Network for Surveillance of Resistant Pathogens (ANSORP).

To investigate the nasal carriage of antibiotic-resistant pneumococci by children, anterior nasal swabs were done for 4963 children <5 years old in 11 countries in Asia and the Middle East. In total, 1105 pneumococci isolates (carriage rate, 22.3%) were collected, 35.8% of which were found to be nonsusceptible to penicillin. Prevalence of penicillin nonsusceptibility was highest in Taiwan (91.3%), followed by Korea (85.8%), Sri Lanka (76.5%), and Vietnam (70.4%). Penicillin resistance was related to residence in urban areas, enrollment in day care, and a history of otitis media. The most common serogroups were 6 (21.5%), 23 (16.5%), and 19 (15.7%). The most common clone, as assessed by pulsed-field gel electrophoresis, was identical to the Spanish 23F clone and to strains of invasive isolates from adult patients. Data in this study documented the high rate of penicillin or multidrug resistance among isolates of pneumococci carried nasally in children in Asia and the Middle East and showed that this is due to the spread of a few predominant clones in the region.

Anti-Bacterial Agents↗
PubMed2001

Diagnosis and treatment of upper respiratory tract infections in the primary care setting.

BACKGROUND: Acute respiratory tract infections such as acute exacerbations of chronic bronchitis (AECB), acute otitis media (AOM), and acute bacterial rhinosinusitis (ABRS) account for approximately 75% of antibiotic prescriptions written and are among the leading reasons for physician office visits in the United States. Resistance of the predominant pathogens in respiratory tract infections (Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis) to available antibiotics has led clinicians to reevaluate the diagnosis and management of these infections. OBJECTIVE: The purpose of this review is to provide primary care practitioners with an accessible combined resource for the management of AECB, AOM, and ABRS. METHODS: This review was based on discussions from a roundtable meeting (sponsored by an educational grant from GlaxoSmithKline) that convened clinicians versed in the management of upper and lower respiratory tract infections. In addition, primary articles were identified by a MEDLINE search and through secondary sources. RESULTS: To reduce the prevalence of resistance, judicious and appropriate use of antibiotics must be implemented in clinical practice. With accurate diagnosis of bacterial and nonbacterial conditions, and patient education on antibiotic use and misuse, the excessive use of antibiotics and ensuing resistance can be reduced. The incorporation of pharmacokinetic and pharmacodynamic data with minimum inhibitory concentration values can provide a more comprehensive assessment of antibiotic activity in vivo. Stratification of patients with AECB according to patient characteristics and frequency of exacerbation can be used to determine which patients will benefit from antibiotic treatment and to guide clinicians in their choice of antibiotic. The Drug-Resistant Streptococcus pneumoniae Therapeutic Working Group has issued recommendations on the management of AOM based on prior antibiotic therapy, which is a risk factor for antimicrobial resistance. The Sinus and Allergy Health Partnership guidelines for the treatment of ABRS in adults and children are based on the predicted efficacy of various antibiotics as well as patient age, severity of disease, likelihood of bacterial infection, likelihood of spontaneous resolution, and in vitro susceptibility of the predominant pathogens based on pharmacokinetic and pharmacodynamic breakpoints. CONCLUSIONS: Guidelines for the management of AECB, AOM, and ABRS emphasize the importance of differentiating between bacterial and nonbacterial infections, choosing an antibiotic based on the likelihood of infection with resistant pathogens, and providing coverage against the predominant pathogens. The judicious use of antibiotics also has been identified as an instrumental part of controlling unnecessary antibiotic use and subsequent resistance.

Acute Disease↗
PubMed2001

High prevalence of carriage of antibiotic-resistant Streptococcus pneumoniae in children in Kampala Uganda.

There are few data on antibiotic-resistant Streptococcus pneumoniae in Uganda. A total of 191 healthy children in Kampala, Uganda were screened for nasopharyngeal carriage of S. pneumoniae; 118 (62%) of the children were carriers. Antimicrobial susceptibility and serotype of 115 strains was determined. Ninety-six (83.5%) of the isolates were of intermediate resistance to penicillin and 19 (16.5%) were susceptible. All strains were susceptible to cefotaxime. The rates of resistance to other drugs were trimethoprim-sulphamethoxazole (83.5%), tetracycline (28.7%) and chloramphenicol (10.4%). All strains were susceptible to rifampicin, erythromycin and clindamycin. Serogroups 6, 9, 14, 19 and 23 accounted for 80% of the isolates. These data show that the rate of carriage of antibiotic-resistant pneumococci by children is high in Kampala, Uganda.

Anti-Bacterial Agents↗
PubMed2001

Optimisation of antimicrobial therapy using pharmacokinetic and pharmacodynamic parameters.

To understand the relationship between drug dose and efficacy, pharmacokinetic (PK) and pharmacodynamic (PD) characteristics need to be integrated. Patterns of antimicrobial activity fall into one of two major patterns: time-dependent killing and concentration-dependent killing. Time-dependent killing is characteristic of many antibiotic classes, such as beta-lactams and macrolides, and seeks to optimise the duration of exposure of a pathogen to an antimicrobial. The major PK/PD parameter correlating with efficacy of time-dependent antimicrobials is the serum concentration present for 40-50% of the dosing interval, and this concentration is the susceptibility limit or breakpoint for the dosing regimen used. The second pattern, concentration-dependent killing, seeks to maximise antimicrobial concentration and is seen with aminoglycosides, quinolones and azalides. The major PK/PD parameter correlating with efficacy of these agents is the 24-h area under the curve to MIC ratio, which should be > or =25 for less severe infections or in immunocompetent hosts, and > or =100 in more severe infections or in immunocompromised hosts. PK/PD breakpoints for concentration-dependent agents can therefore be calculated from the formula AUC divided by 25. This enables development of PK/PD breakpoints based on the above parameters for time- and concentration-dependent agents for defined dosing regimens. For an antimicrobial to be useful empirically, the MIC90s of the agent against the common pathogens responsible for the disease being treated should be below the PK/PD breakpoint. This is particularly important for oral dosing regimens for treating emerging resistant respiratory tract pathogens, where efficacy against the predominant pathogens, Streptococcus pneumoniae and Haemophilus influenzae, is required.

Anti-Bacterial Agents↗
PubMed2001

Methicillin-resistant Staphylococcus aureus sepsis associated with the transfusion of contaminated platelets: a case report.

BACKGROUND: Platelet transfusion-associated sepsis is usually due to donor skin flora introduced into the unit during phlebotomy. An unusual case of a platelet component contaminated with methicillin-resistant Staphylococcus aureus (MRSA) is reported. CASE REPORT: A 54-year-old man, terminally ill with progressive non-Hodgkin's lymphoma, developed fever and hypotension during a platelet transfusion. He was receiving multiple antibiotics, including vancomycin. Blood cultures taken soon after transfusion were negative. An aliquot taken from the platelet pool grew MRSA at a count of 1.6 x 10(8) CFUs per mL. One of the individual bags constituting the pool showed MRSA at a count of 5.1 x 10(8) CFUs per mL. The patient died soon after the platelet transfusion. This case was reported to the FDA and submitted to the BaCon Study. The identity of the isolate and its methicillin resistance were confirmed by the CDC as part of the BaCon Study protocol. The source of contamination of the implicated unit could not be established with certainty. CONCLUSION: The emergence of antimicrobial-resistant organisms poses additional challenges for the diagnosis and treatment of transfusion-associated sepsis. Measures to prevent or intercept the transfusion of contaminated platelets should be developed.

Blood Platelets↗
PubMed2001

Single- and multi-step resistance selection study of gemifloxacin compared with trovafloxacin, ciprofloxacin, gatifloxacin and moxifloxacin in Streptococcus pneumoniae.

The ability of sequential subcultures in subinhibitory concentrations of gemifloxacin, trovafloxacin, ciprofloxacin, gatifloxacin and moxifloxacin to select resistant mutants was studied in 16 pneumococci [eight with ciprofloxacin MICs (mg/L) 0.25-1; four with 8-16; four with 16-32]. Subculturing was done 50 times, or until mutants with elevated MICs (> or = 4 x) to the selecting drug emerged. Subculturing in gemifloxacin selected six resistant mutants (gemifloxacin MICs 2 mg/L); trovafloxacin selected nine (trovafloxacin MICs 2-4 mg/L); ciprofloxacin selected 11 (ciprofloxacin MICs 8-128 mg/L); gatifloxacin selected 13; and moxifloxacin selected 12 (gatifloxacin or moxifloxacin MICs 2-16 mg/L). DNA sequencing showed that most mutants had mutations in ParC at Ser-79 or Asp-83 and in GyrA at Ser-81 or Glu-85; some mutants also had mutations in ParE or GyrB. Some new mutations were found in ParE or GyrB that have not yet been reported; GyrB mutation might be associated with moxifloxacin resistance. Both DNA gyrase and topoisomerase IV were thought to be the target of gemifloxacin; gemifloxacin also selected mutants with single modifications in gyrA, parC or parE alone among derived mutants by repeated exposure to subinhibitory concentrations of fluoroquinolones. In the presence of reserpine, most mutants had lower MICs of ciprofloxacin and gemifloxacin (4-32 x), and gatifloxacin (4-8 x), suggesting an efflux mechanism; none had lower trovafloxacin and moxifloxacin MICs. All quinolones tested selected for resistance; judicious use and proper dosing will be necessary to avoid resistance selection of newer broad-spectrum fluoroquinolones.

Anti-Infective Agents↗
PubMed2001

Evaluation of PCR primers to screen for Streptococcus pneumoniae isolates and beta-lactam resistance, and to detect common macrolide resistance determinants.

Pneumococcal isolates (n = 148) from various countries (mostly from the USA) were tested by a primer set for PCR. Thirty-eight (86.4%) of the 44 penicillin G-susceptible isolates (MIC < or = 0.06 mg/L) had unaltered pbps, while six isolates (13.6%) had either one or two alterations in pbps. Of 47 penicillin G-resistant strains (MIC > or = 2 mg/L), 41 isolates (87.2%) had all three pbps altered, six isolates (12.8%) had altered pbp1a + 2x. Various combinations of altered pbp were seen in penicillin G-intermediate isolates. Prevalence of macrolide resistance genes mef(A) and erm(B) in isolates was clearly reflected by their MICs. All isolates were positive for lytA. The primers were useful for screening for Streptococcus pneumoniae and beta-lactam resistance, and for detection of common macrolide resistance determinants.

Anti-Bacterial Agents↗
PubMed2001

Bacteriologic and clinical efficacy of high dose amoxicillin/clavulanate in children with acute otitis media.

OBJECTIVES: To determine the bacteriologic and clinical efficacy of high dose amoxicillin/clavulanate (90/6.4 mg/kg/day) against common bacterial pathogens causing acute otitis media (AOM), including penicillin-resistant Streptococcus pneumoniae (PRSP). METHODS: In this open label multicenter study, 521 infants and children with AOM [mean age, 18.6 months; age < 24 months, n = 375 (72%)] were treated with amoxicillin/clavulanate 90/6.4 mg/kg/day in two divided doses for 10 days. Bilateral otitis media, previous episodes of AOM, antibiotic treatment within 3 months and day-care attendance were recorded in 60.1, 35.7, 50.2 and 38.2% of the children, respectively. Tympanocentesis was performed before the first dose and repeated on Days 4 to 6 for all children with S. pneumoniae at 22 centers and for all children with any pathogen at 3 centers. Clinical response was assessed at end of therapy. RESULTS: Pathogens were isolated from 355 (68%) of 521 enrolled children; 180 children underwent repeat tympanocentesis and were bacteriologically evaluable. Baseline pathogens were S. pneumoniae (n = 122 enrolled/93 bacteriologically evaluable), Haemophilus influenzae (n = 160/51), both (n = 37/32) and others (n = 36/4). Pathogens were eradicated from 172 (96%) of 180 bacteriologically evaluable children. Overall 122 (98%) of 125 isolates of S. pneumoniae were eradicated, including 31 (91%) of 34 PRSP isolates (penicillin MICs 2 to 4 micrograms/ml). Seventy-eight (94%) of 83 isolates of H. influenzae were eradicated. Symptoms and otoscopic signs of acute inflammation were completely resolved or improved on Days 12 to 15 in 263 (89%) of 295 clinically evaluable children with bacteriologically documented AOM. CONCLUSIONS: On the basis of bacteriologic outcome on Days 4 to 6 and clinical outcome on Days 12 to 15, we found that high dose amoxicillin/clavulanate (90/6.4 mg/kg/day) was highly efficacious in children with AOM, including those most likely to fail treatment, namely children < 24 months of age and those with infectious caused by PRSP.

Acute Disease↗
PubMed2001

Prevalence and mechanisms of macrolide resistance in Streptococcus pyogenes in Santiago, Chile.

Thirty-two macrolide-resistant Streptococcus pyogenes isolates were found among 594 clinical isolates collected from 1990 to 1998 in Santiago, Chile, for an overall prevalence of 7.2%. Among the 32 resistant isolates, 28 (87.5%) presented the M phenotype and 4 (12. 5%) presented the MLS(B) phenotype. Serotyping and pulsed-field gel electrophoresis analysis showed genetic diversity among the resistant isolates.

Anti-Bacterial Agents↗
PubMed2001

Susceptibilities of Haemophilus influenzae and Moraxella catarrhalis to ABT-773 compared to their susceptibilities to 11 other agents.

The activity of the ketolide ABT-773 against Haemophilus and Moraxella was compared to those of 11 other agents. Against 210 Haemophilus influenzae strains (39.0% beta-lactamase positive), microbroth dilution tests showed that azithromycin and ABT-773 had the lowest MICs (0.5 to 4.0 and 1.0 to 8.0 microg/ml, respectively), followed by clarithromycin and roxithromycin (4.0 to >32.0 microg/ml). Of the beta-lactams, ceftriaxone had the lowest MICs (</=0.004 to 0.016 microg/ml), followed by cefixime and cefpodoxime (0.008 to 0.125 and </=0.125 to 0.25 microg/ml, respectively), amoxicillin-clavulanate (0.125 to 4.0 microg/ml), and cefuroxime (0. 25 to 8.0 microg/ml). Amoxicillin was only active against beta-lactamase-negative strains, and cefprozil had the highest MICs of all oral cephalosporins tested (0.5 to >32.0 microg/ml). Against 50 Moraxella catarrhalis strains, all of the compounds except amoxicillin and cefprozil were active. Time-kill studies against 10 H. influenzae strains showed that ABT-773, at two times the MIC, was bactericidal against 9 of 10 strains, with 99% killing of all strains at the MIC after 24 h; at 12 h, ABT-773 gave 90% killing of all strains at two times the MIC. At 3 and 6 h, killing by ABT-773 was slower, with 99.9% killing of four strains at two times the MIC after 6 h. Similar results were found for azithromycin, with slightly slower killing by erythromycin, clarithromycin, and roxithromycin, especially at earlier times. beta-Lactams were bactericidal against 8 to 10 strains at two times the MIC after 24 h, with slower killing at earlier time periods. Most compounds gave good killing of five M. catarrhalis strains, with beta-lactams killing more rapidly than other drugs. ABT-773 and azithromycin gave the longest postantibiotic effects (PAEs) of the ketolide-macrolide-azalide group tested (4.4 to >8.0 h), followed by clarithromycin, erythromycin, and roxithromycin. beta-Lactam PAEs were similar and shorter than those of the ketolide-macrolide-azalide group for all strains tested.

Anti-Bacterial Agents↗
PubMed2001

Activities of a new fluoroketolide, HMR 3787, and its (des)-fluor derivative RU 64399 compared to those of telithromycin, erythromycin A, azithromycin, clarithromycin, and clindamycin against macrolide-susceptible or -resistant Streptococcus pneumoniae and S. pyogenes.

Activities of HMR 3787 and RU 64399 were compared to those of three macrolides, telithromycin, and clindamycin against 175 Streptococcus pneumoniae isolates and 121 Streptococcus pyogenes isolates. HMR3787 and telithromycin were the most active compounds tested against pneumococci. Telithromycin and RU 64399 were equally active against macrolide-susceptible (MICs, 0.008 to 0.06 microg/ml) and -resistant S. pyogenes isolates, but HMR 3787 had lower MICs for ermB strains.

Anti-Bacterial Agents↗
PubMed2001

Comparative antianaerobic activity of BMS 284756.

Agar dilution MIC methodology was used to compare the activity of BMS 284756 with those of ciprofloxacin, levofloxacin, moxifloxacin, trovafloxacin, amoxicillin-clavulanate, piperacillin-tazobactam, imipenem, clindamycin, and metronidazole against 357 anaerobes. Overall, the respective MICs at which 50% of the isolates tested were inhibited (MIC(50)s) and MIC(90)s (in micrograms per milliliter) were as follows: BMS 284756, 0.5 and 2.0; ciprofloxacin, 2.0 and 16.0; levofloxacin, 1.0 and 8.0; moxifloxacin, 0.5 and 4.0; trovafloxacin, 0.5 and 2.0; amoxicillin-clavulanate, 0.5 and 2.0; piperacillin-tazobactam, 0.25 and 8.0; imipenem, 0.06 and 1.0; clindamycin, 0.25 and 8.0; and metronidazole, 1.0 and >16.0. BMS 284756 is a promising new quinolone with excellent antianaerobic activity.

Anti-Infective Agents↗
PubMed2001

Evidence-based guidelines for treatment of bacterial respiratory tract infections in the era of antibiotic resistance.

Antimicrobial resistance in bacterial respiratory tract pathogens is a rapidly evolving and increasingly disconcerting problem. Major factors that have contributed to resistance are inappropriate prescribing of antibiotics for viral infections and the use of antibiotics with poor activity. The treatment of respiratory tract infections is significantly affected by resistance in organisms such as Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Resistance to beta-lactams, sulfonamides, and macrolides continues to rise. Evidence-based guidelines, founded on clinical and bacteriological outcomes, are imperative to treat patients effectively, to limit the spread of these pathogens, and to minimize further development of resistance. Pharmacokinetic and pharmacodynamic parameters have recently been shown to correlate with clinical outcome, and offer a more rational approach to predicting antimicrobial efficacy and determining clinically relevant susceptibility breakpoints.

Anti-Bacterial Agents↗