Biomedical subjects

Michael R Jacobs

Publications and source records attributed to Michael R Jacobs.

83 records · Page 5Linked to original sources

PubMed2002

Multinational study of pneumococcal serotypes causing acute otitis media in children.

BACKGROUND: Streptococcus pneumoniae is a major cause of acute otitis media (AOM) in young children. More than 90 immunologically distinct pneumococcal serotypes have been identified, but limited information is available regarding their relative importance in AOM. METHODS: We analyzed nine existing datasets comprising pneumococcal isolates from middle ear fluid samples collected from 1994 through 2000 from 3,232 children with AOM from Finland, France, Greece, Israel, several East European countries, the US and Argentina. We examined the distribution of pneumococcal serotypes in relation to several demographic and epidemiologic variables, including gender, age, antibiotic resistance and source of culture material. RESULTS: The major serotypes identified included 19F and 23F, each comprising 13 to 25% of pneumococcal middle ear fluid isolates in most datasets; 14 and 6B, comprising 6 to 18%; whereas 6A, 19A and 9V each comprised 5 to 10%. Despite differences in location, study design and antibiotic susceptibility, each major serotype was prominent in most age groups of each dataset. Serotypes represented in the 7-valent pneumococcal conjugate vaccine (PCV-7, 4, 6B, 9V, 14, 18C, 19F, 23F) accounted for 60 to 70% of all pneumococcal isolates in the 6- to 59-month age range, but only 40 to 50% of isolates in children <6 or >/=60 months old. Serotype 3 and, in certain datasets, serotypes 1 and 5, were more important in the <6- and >/=60-month age groups. In each age group vaccine-related serotypes (mainly 6A and 19A) comprised an additional 10 to 15% of all pneumococcal isolates. Four serotypes (23F, 19F, 14 and 6B) accounted for 83% of all penicillin-resistant observations. CONCLUSIONS: This analysis of several geographically diverse datasets indicates that a limited number of serotypes, largely represented in PCV-7, accounted for the majority of episodes of pneumococcal AOM in children between 6 and 59 months of age. Certain serotypes appeared to be relatively more significant in children <6 months or >59 months of age.

Age Factors↗

PubMed2002

In vitro antianaerobic activity of ertapenem (MK-0826) compared to seven other compounds.

Ertapenem, imipenem, meropenem, ceftriaxone, piperacillin, piperacillin-tazobactam, clindamycin, and metronidazole were agar dilution MIC tested against 431 anaerobes. Imipenem, meropenem, and ertapenem were the most active beta-lactams (MICs at which 50% of the strains are inhibited [MIC(50)s], 0.125 to 0.25 microg/ml; MIC(90)s, 1.0 to 2.0 microg/ml). Time-kill studies revealed that ertapenem at two times the MIC was bactericidal for 9 of 10 strains after 48 h. The kinetics for other beta-lactams were similar to those of ertapenem.

Bacteria, Anaerobic↗

PubMed2002

Antipneumococcal activity of BMS 284756 compared to those of six other agents.

Antipneumococcal activity of BMS 284756 was compared to those of six agents by MIC and time-kill methodologies. BMS 284756 had the lowest MICs compared to those of ciprofloxacin, levofloxacin, and moxifloxacin against quinolone-susceptible (< or =0.016 to 0.06 microg/ml) and quinolone-resistant (0.03 to 1 microg/ml) pneumococci. BMS 284756 was bactericidal against 11 of 12 strains at two times the MIC after 24 h.

Anti-Infective Agents↗

PubMed2002

Antipneumococcal activity of ertapenem (MK-0826) compared to those of other agents.

The activities of ertapenem (MK-0826) and eight other agents against a range of penicillin-susceptible and -resistant pneumococci were tested by determination of MICs by the microdilution method and by the time-kill methodology. For 125 penicillin-susceptible, 74 penicillin-intermediate, and 86 penicillin-resistant pneumococci, the MICs at which 50% of isolates are inhibited (MIC(50)s) and MIC(90)s, as determined by the microdilution method, were as follows: for ertapenem, 0.016 and 0.03, 0.125 and 0.5, and 0.5 and 1.0 microg/ml for penicillin-susceptible, penicillin-intermediate, and penicillin-resistant pneumococci, respectively; for amoxicillin, < or =0.016 and 0.03, 0.25 and 1.0, and 2.0 and 2.0 microg/ml for penicillin-susceptible, penicillin-intermediate, and penicillin-resistant pneumococci, respectively; for cefprozil, 0.125 and 0.25, 1.0 and 8.0, and 16.0 and 16.0 microg/ml for penicillin-susceptible, penicillin-intermediate, and penicillin-resistant pneumococci, respectively; for cefepime, < or =0.016 and 0.06, 0.5 and 1.0, and 1.0 and 2.0 microg/ml for penicillin-susceptible, penicillin-intermediate, and penicillin-resistant pneumococci, respectively; for ceftriaxone, < or =0.016 and 0.06, 0.25 and 1.0, and 1.0 and 2.0 microg/ml for penicillin-susceptible, penicillin-intermediate, and penicillin-resistant pneumococci, respectively; for imipenem, < or =0.008 and < or =0.008, 0.03 and 0.25, and 0.25 and 0.25 microg/ml for penicillin-susceptible, penicillin-intermediate, and penicillin-resistant pneumococci, respectively; for meropenem, < or =0.008 and 0.016, 0.125 and 0.5, and 0.5 and 1.0 microg/ml for penicillin-susceptible, penicillin-intermediate, and penicillin-resistant pneumococci, respectively; and for clarithromycin, 1.0 and >32.0, 1.0 and >32.0, and >32.0 and >32.0 microg/ml for penicillin-susceptible, penicillin-intermediate, and penicillin-resistant pneumococci, respectively. For 64 strains for which quinolone MICs were increased (ciprofloxacin MICs, > or =4.0 microg/ml), the MIC(90) of ertapenem was 1.0 microg/ml and the MIC(90)s of the other beta-lactams tested and clarithromycin were >32.0 microg/ml. Against four penicillin-susceptible, four penicillin-intermediate, and four penicillin-resistant strains, testing by the time-kill methodology showed that ertapenem at two times the MIC was bacteriostatic (99% killing) after 12 h and bactericidal (99.9% killing) against all strains by 24 h, with 90% killing of all strains at two times the MIC after 6 h. At the MIC, ertapenem was bacteriostatic against all strains tested after 24 h. Although the bactericidal activity of imipenem at the MIC after 24 h was significantly greater than that of ertapenem, the kinetics of the two drugs at two times the MIC were similar after 24 h. The killing kinetics of clarithromycin were slower than those of ertapenem and other agents, with clarithromycin at two times the MIC having bactericidal activity against seven of eight macrolide-susceptible strains after 24 h.

Amoxicillin↗

PubMed2002

Susceptibilities to telithromycin and six other agents and prevalence of macrolide resistance due to L4 ribosomal protein mutation among 992 Pneumococci from 10 central and Eastern European countries.

The macrolide and levofloxacin susceptibilities of 992 isolates of Streptococcus pneumoniae from clinical specimens collected in 1999 and 2000 were determined in 10 centers in Central and Eastern European countries. The prevalences of penicillin G-intermediate (MICs, 0.125 to 1 microg/ml) and penicillin-resistant (MICs, < or =2 microg/ml) Streptococcus pneumoniae isolates were 14.3 and 16.6%, respectively. The MICs at which 50% of isolates are inhibited (MIC(50)s) and the MIC(90)s of telithromycin were 0.016 and 0.06 microg/ml, respectively; those of erythromycin were 0.06 and >64 microg/ml, respectively; those of azithromycin were 0.125 and >64 microg/ml, respectively; those of clarithromycin were 0.03 and >64 microg/ml, respectively; and those of clindamycin were 0.06 and >64 microg/ml, respectively. Erythromycin resistance was found in 180 S. pneumoniae isolates (18.1%); the highest prevalence of erythromycin-resistant S. pneumoniae was observed in Hungary (35.5%). Among erythromycin-resistant S. pneumoniae isolates, strains harboring erm(B) genes (125 strains [69.4%]) were found to be predominant over strains with mef(E) genes (25 strains [13.4%]), L4 protein mutations (28 strains [15.6%]), and erm(A) genes (2 strains [1.1%]). Similar pulsed-field gel electrophoresis patterns suggested that some strains containing L4 mutations from the Slovak Republic, Bulgaria, and Latvia were clonally related. Of nine strains highly resistant to levofloxacin (MICs, >8 microg/ml) six were isolated from Zagreb, Croatia. Telithromycin at < or =0.5 microg/ml was active against 99.8% of S. pneumoniae isolates tested and may be useful for the treatment of respiratory tract infections caused by macrolide-resistant S. pneumoniae isolates.

Age Factors↗

PubMed2002

Susceptibility to telithromycin in 1,011 Streptococcus pyogenes isolates from 10 central and Eastern European countries.

Among 1,011 recently isolated Streptococcus pyogenes isolates from 10 Central and Eastern European centers, the MICs at which 50% of isolates are inhibited (MIC(50)s) and the MIC(90)s were as follows: for telithromycin, 0.03 and 0.06 microg/ml, respectively; for erythromycin, azithromycin, and clarithromycin, 0.06 to 0.125 and 1 to 8 microg/ml, respectively; and for clindamycin, 0.125 and 0.125 microg/ml, respectively. Erythromycin resistance occurred in 12.3% of strains. Erm(A) [subclass erm(TR)] was most commonly encountered (60.5%), followed by mef(A) (23.4%) and erm(B) (14.5%). At <0.5 microg/ml, telithromycin was active against 98.5% of the strains tested.

Anti-Bacterial Agents↗

PubMed2002

Effects of amino acid alterations in penicillin-binding proteins (PBPs) 1a, 2b, and 2x on PBP affinities of penicillin, ampicillin, amoxicillin, cefditoren, cefuroxime, cefprozil, and cefaclor in 18 clinical isolates of penicillin-susceptible, -intermediate, and -resistant pneumococci.

Amino acid alterations in or flanking conserved motifs making up the active binding sites of penicillin-binding proteins (PBPs) 1a, 2b, and 2x of pneumococci were correlated with changes in affinities of penicillin, ampicillin, amoxicillin, cefditoren, cefuroxime, cefprozil, and cefaclor for these PBPs. Four penicillin-susceptible (PSSP), eight penicillin-intermediate (PISP), and six penicillin-resistant (PRSP) pneumococci were studied by DNA sequencing of the penicillin-binding sites of the pbp1a, -2x, and -2b genes of strains and by determining 50% inhibitory concentrations of the seven agents for PBP1a, -2x, and -2b. Two PSSP strains had alterations in PBP2x (L(546)-->V) (one strain) or PBP2b (T(445)-->A) (one strain). All eight PISP strains had at least two alterations--T(338)-->P or A or H(394)-->Y in PBP2X and T(445)-->A in BPB2b. All PRSP strains had the same changes seen in PISP strains, as well as T(371)-->A or S substitutions in PBP1a. The two most resistant PRSP strains had a second change in PBP2x (M(339)-->F) in a conserved motif. The affinities of penicillin and ampicillin for all three PBPs were decreased for PRSP and most PISP strains. The affinity of amoxicillin for PBP1a and -2x was decreased only for PRSP. Cefaclor and cefprozil showed decreased affinity of PRSP but not PISP for all three PBPs. Cefuroxime showed decreased affinity of PISP and PRSP for PBP1a and -2x but no change for PBP2b. Cefditoren showed no difference in PBP affinity based on penicillin or cefditoren MICs, indicating a different PBP target for this agent. Overall, the MICs for and PBP affinities of the strains correlated with the changes found in the PBP active binding sites.

Adult↗

PubMed2002

In vitro selection of resistance in Haemophilus influenzae by amoxicillin-clavulanate, cefpodoxime, cefprozil, azithromycin, and clarithromycin.

Abilities of amoxicillin-clavulanate, cefpodoxime, cefprozil, azithromycin, and clarithromycin to select resistant mutants of Haemophilus influenzae were tested by multistep and single-step methodologies. For multistep studies, 10 random strains were tested: 5 of these were beta-lactamase positive. After 50 daily subcultures in amoxicillin-clavulanate, MICs did not increase more than fourfold. However, cefprozil MICs increased eightfold for one strain. Clarithromycin and azithromycin gave a >4-fold increase in 8 and 10 strains after 14 to 46 and 20 to 50 days, respectively. Mutants selected by clarithromycin and azithromycin were associated with mutations in 23S rRNA and ribosomal proteins L4 and L22. Three mutants selected by clarithromycin or azithromycin had alterations in ribosomal protein L4, while five had alterations in ribosomal protein L22. Two mutants selected by azithromycin had mutations in the gene encoding 23S rRNA: one at position 2058 and the other at position 2059 (Escherichia coli numbering), with replacement of A by G. One clone selected by clarithromycin became hypersusceptible to macrolides. In single-step studies azithromycin and clarithromycin had the highest mutation rates, while amoxicillin-clavulanate had the lowest. All resistant clones were identical to parents as observed by pulsed-field gel electrophoresis. The MICs of azithromycin for azithromycin-resistant clones were 16 to >128 micro g/ml, and those of clarithromycin for clarithromycin-resistant clones were 32 to >128 micro g/ml in multistep studies. For strains selected by azithromycin, the MICs of clarithromycin were high and vice versa. After 50 daily subcultures in the presence of drugs, MICs of amoxicillin-clavulanate and cefpodoxime against H. influenzae did not rise more than fourfold, in contrast to cefprozil, azithromycin, and clarithromycin, whose MICs rose to variable degrees.

Amino Acid Sequence↗

PubMed2002

Antistreptococcal activity of telithromycin compared with seven other drugs in relation to macrolide resistance mechanisms in Russia.

The susceptibilities of 468 recent Russian clinical Streptococcus pneumoniae isolates and 600 Streptococcus pyogenes isolates, from 14 centers in Russia, to telithromycin, erythromycin, azithromycin, clarithromycin, clindamycin, levofloxacin, quinupristin-dalfopristin, and penicillin G were tested. Penicillin-nonsusceptible S. pneumoniae strains were rare except in Siberia, where their prevalence rate was 13.5%: most were penicillin intermediate, but for three strains (two from Smolensk and one from Novosibirsk) the MICs of penicillin G were 4 or 8 micro g/ml. Overall, 2.5% of S. pneumoniae isolates were resistant to erythromycin. Efflux was the prevalent resistance mechanism (five strains; 41.7%), followed by ribosomal methylation encoded by constitutive erm(B), which was found in four isolates. Ribosomal mutation was the mechanism of macrolide resistance in three isolates; one erythromycin-resistant S. pneumoniae isolate had an A2059G mutation in 23S rRNA, and two isolates had substitution of GTG by TPS at positions 69 to 71 in ribosomal protein L4. All S. pyogenes isolates were susceptible to penicillin, and 11% were erythromycin resistant. Ribosomal methylation was the most common resistance mechanism for S. pyogenes (89.4%). These methylases were encoded by erm(A) [subclass erm(TR)] genes, and their expression was inducible in 96.6% of isolates. The rest of the erythromycin-resistant Russian S. pyogenes isolates (7.6%) had an efflux resistance mechanism. Telithromycin was active against 100% of pneumococci and 99.2% of S. pyogenes, and levofloxacin and quinupristin-dalfopristin were active against all isolates of both species.

Anti-Bacterial Agents↗

PubMed2002

Effects of various test media on the activities of 21 antimicrobial agents against Haemophilus influenzae.

As considerable variation in the antimicrobial susceptibility of Haemophilus influenzae has been reported, the effects of various test media on the susceptibility of H. influenzae were studied. MICs were determined by three laboratories for 21 antimicrobial agents against a panel of 100 selected isolates. Testing was performed using a reference NCCLS frozen broth microdilution method with Haemophilus test medium (HTM) broth and dried commercial MIC trays rehydrated with the following media: in-house and commercially prepared HTM broth, Mueller-Hinton broth with 2% lysed horse blood and NAD, IsoSensitest broth with 2% lysed horse blood and NAD, and IsoSensitest broth-based HTM. Overall, all results were very reproducible, with the MIC at which 50% of the isolates tested are inhibited (MIC(50)), MIC(90), and geometric mean MIC being within one doubling dilution by all six methods and at all three testing centers for 15 of the 21 agents tested. Interlaboratory differences were more marked than intralaboratory differences or differences among media. Cefprozil, cefaclor, and trimethoprim-sulfamethoxazole results differed the most, while results for ampicillin, amoxicillin-clavulanic acid, cefdinir, cefixime, ceftriaxone, and clarithromycin were the most reproducible. However, these variations in results caused considerable differences in susceptibility rates for agents for which NCCLS susceptible breakpoints were close to the geometric mean MIC, particularly for cefaclor and cefprozil. This was much less of a problem when pharmacokinetic-pharmacodynamic breakpoints were used. Reproducible susceptibility results were obtained for a wide range of agents against H. influenzae in three laboratories using a variety of media that support the growth of this fastidious species.

Anti-Bacterial Agents↗

PubMed2002

Hospital admissions resulting from preventable adverse drug reactions.

BACKGROUND: Adverse drug reactions (ADRs) are a significant cause of hospital admissions. These events can lead to significant morbidity and mortality and financial costs. ADRs that may be preventable might be considered a form of medication error. OBJECTIVE: To assess the potential preventability of ADRs directly related to a patient's hospital admission. METHODS: A retrospective chart review of 437 ADRs occurring during an 11-month period was conducted at a university hospital. A subset of these events leading to hospital admissions was identified for further review. Those that resulted in admission were further examined to determine probability of causality, severity, and preventability. RESULTS: Over 11 months, 158 ADRs were directly related to hospital admission. The relationship of these admissions to drug exposure was determined to be probable or highly probable in 154 (97.4%) of these cases. From this group, 96 (62.3%) of these events were considered potentially preventable, with 23 (24%) considered severe to life-threatening. Characteristics associated with these ADRs included documentation of a toxic drug concentration or abnormal laboratory value (80%), inadequate monitoring of a patient's drug therapy (67%), inappropriate dose (51%), patient noncompliance (33%), drug-drug interaction (26%), contraindication to therapy (3%), and documented allergy (1%). These ADRs resulted in 595 hospital days, with an average length of stay of 6.1 days. CONCLUSIONS: ADRs leading to hospital admissions are often preventable. Approximately 25% of these events were serious to life-threatening. Most resulted from inadequate monitoring of therapy or inappropriate dosing. Patient noncompliance and drug interactions were also common causes. Multidisciplinary prevention strategies among physicians, pharmacists, other healthcare professionals, and patients focusing on communication and education should be targeted.

Adolescent↗