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R N Jones

Publications and source records attributed to R N Jones.

At least 235 records · Page 13Linked to original sources
PubMed1999

Evaluation of reference dilution test methods for antimicrobial susceptibility testing of Pseudomonas aeruginosa strains isolated from patients with cystic fibrosis.

The development of multidrug-resistant Pseudomonas aeruginosa in patients with cystic fibrosis (CF) is most likely a consequence of increasing life expectancy and more prolonged exposure to antibiotics. The optimal method for antibiotic susceptibility testing of CF strains, particularly mucoid P. aeruginosa strains, is unknown. Antimicrobial susceptibilities of 48 CF strains (25 mucoid) and 50 non-CF strains to 12 anti-Pseudomonas agents were tested by both agar dilution and commercially custom-prepared broth microdilution plates (PML Microbiologicals, Portland, Oreg.) in three laboratories simultaneously to determine if broth microdilution could substitute for agar dilution as the reference method in subsequent studies. Comparison of MICs generated by agar dilution and broth microdilution demonstrated correlation coefficients (r) exceeding 0.85 for all agents tested; correlation was excellent for aminoglycosides (r >/= 0.92) and very good for beta-lactam agents including agents paired with a beta-lactamase inhibitor (r >/= 0.87) and for ciprofloxacin (r = 0.86). Correlation was not improved by 48-h readings, but correlation between 24- and 48-h readings ranged between 0.91 and 0.98 for both methods. Interlaboratory variations were minimal, as the percentage of acceptable variations was 94% for both methods, and serious discords were infrequent (<2% of comparisons). However, CF strains were more likely to have serious discords than were non-CF strains (P < 0. 0001), although mucoid strains were not more likely to have serious discords than were nonmucoid strains. In this study, MICs determined by custom-prepared broth microdilution compared favorably with MICs determined by agar dilution. Thus, this broth microdilution assay can serve as a reference method and facilitate future studies to determine the optimal method for antibiotic susceptibility testing of CF strains.

Cystic Fibrosis↗
PubMed1999

Assessment of laboratory performance with Streptococcus pneumoniae antimicrobial susceptibility testing in the United States: a report from the College of American Pathologists Microbiology Proficiency Survey Program.

OBJECTIVE: To assess the performance of clinical microbiology laboratories in the United States when conducting in vitro susceptibility tests with Streptococcus pneumoniae. METHODS: The results of a nationwide College of American Pathologists Proficiency Survey test sample, in which susceptibility testing of an isolate of S. pneumoniae was performed, were assessed with respect to precision and accuracy. RESULTS: Wide variability was noted among participating laboratories with both minimum inhibitory concentration procedures and disk diffusion susceptibility tests when both methods were applied to S. pneumoniae. Despite this high degree of variation, categorical interpretive errors were uncommon. Numerous laboratories reported results for antimicrobial agents that are not recommended by the National Committee for Clinical Laboratory Standards for tests with S. pneumoniae. CONCLUSIONS: Current susceptibility testing practices with S. pneumoniae in the United States indicate limited precision and a tendency for laboratories to test and report results obtained with antimicrobial agents of questionable therapeutic value against this organism. Continued efforts to standardize susceptibility testing of S. pneumoniae in the United States are warranted. In addition, modifications of existing interpretive criteria may be necessary.

Anti-Bacterial Agents↗
PubMed1999

Comparative in vitro evaluation of dirithromycin tested against recent clinical isolates of Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae, including effects of medium supplements and test conditions on MIC results.

The use of macrolides for treatment of respiratory complaints has been complicated by susceptibility test conditions that adversely effect the in vitro test results and perceived potencies of these compounds. Dirithromycin was studied as to its in vitro activity compared to other macrolides as well as the effects that environmental incubation variations and inoculum concentrations may have on susceptibility results. Dirithromycin was less active than other macrolides tested (azithromycin clarithromycin, erythromycin) against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis with MIC90 values of 16, 32, and 1 microgram/ml, respectively; an activity that was most similar to roxithromycin. This reduced activity may be compensated by the superior pharmacokinetic properties that dirithromycin possesses compared to other members in its class. Method variation studies show that incubation in CO2 environments increase the MIC values for all macrolide compounds and dirithromycin was most effected by pH changes in three in vitro methods tested (Etest [AB BIODISK, Solna, Sweden] broth microdilution, and disk diffusion). Variations in inoculum concentration had minimal effect on dirithromycin potency. In addition the variability (lack of reproducibility) of the test results with dirithromycin were not significant. Dirithromycin is an alternative therapeutic choice among macrolide compounds for treatment of community-acquired respiratory infections caused by various streptococci, Legionella pneumophilia, Mycoplasma pneumoniae and M. catarrhalis, and also possesses a modest in vitro potency versus H. influenzae coupled with excellent pharmacokinetic properties. In vitro tests with dirithromycin will continue to be problematic for H. influenzae because of the adverse effects of recommended CO2 incubation for some standardized methods or commercial products (Etest).

Anti-Bacterial Agents↗
PubMed1998

Multicenter evaluation of the antimicrobial activity for six broad-spectrum beta-lactams in Venezuela using the Etest method. The Venezuelan Antimicrobial Resistance Study Group.

In early 1997, a 15-laboratory surveillance project was initiated in Venezuela to monitor the potency and spectrum of 6 broad-spectrum antimicrobial agents (cefepime, cefotaxime, ceftazidime, piperacillin, piperacillin/tazobactam, and imipenem) tested against approximately 100 organisms per participant center (1297 strains). Ten groups of organisms were tested by the Etest method (AB BIODISK, Solna, Sweden) with results validated by concurrent quality control strain analysis. Results from all centers were tabulated and 96.3% of quality assurance tests were within ranges recommended by the National Committee for Clinical Laboratory Standards. Among the six beta-lactam class drugs tested, imipenem and cefepime were the most active against all isolates tested. Overall, the rank order of susceptibility of the six agents was imipenem (97.2%, susceptible; MIC90 2 micrograms/ml) > cefepime (92.8%; MIC90 6 micrograms/mL) > piperacillin/tazobactam (77.2-83.0%; MIC90 > 256 micrograms/mL) > cefotaxime (72.2%; MIC90 > 256 micrograms/mL) > piperacillin (56.8-65.8%; MIC90 > 256 micrograms/mL) > ceftazidime (64.66%; MIC90 128 micrograms/mL). Both cefepime and imipenem were active against ceftazidime-resistant strains of Enterobactericaeae as well as against Pseudomonas aeruginosa and oxacillin-susceptible staphylococci. Resistance phenotypes consistent with extended spectrum beta-lactamases (ESBLs) and stably derepressed Bush group 1 cephalosporinases were documented in strains of Klebsiella spp. and Enterobacters, respectively. These data should be used to guide empiric therapy with beta-lactams in Venezuela, and additionally will provide a reference statistical baseline to which future studies in this nation can be compared.

Acinetobacter↗
PubMed1998

Multicenter evaluation of the in vitro activity of six broad-spectrum beta-lactam antimicrobial agents in Puerto Rico. The Puerto Rico Antimicrobial Resistance Study Group.

The minimum inhibitory concentrations of 6 broad-spectrum beta-lactam antimicrobial agents were determined by use of the Etest versus a total of 569 bacteria in 7 Puerto Rican hospital laboratories. These included 342 recent clinical isolates of Enterobacteriaceae, 63 Pseudomonas aeruginosa, 54 Acinetobacter species, and 110 oxacillin-susceptible staphylococci. Extended spectrum beta-lactamase production was noted among 11% of Klebsiella pneumoniae isolates. Hyperproduction of Amp C cephalosporinase was observed with > 20% of isolates of Enterobacter spp., Serratia spp., and Citrobacter freundii. The overall rank order of activity of the six beta-lactams examined in this study versus all clinical isolates was imipenem (95.8% susceptible) > cefepime (91.1%) > piperacillin/ tazobactam (82.3%) > cefotaxime (77.6%) > piperacillin (72.5%) > ceftazidime (67.0%).

Anti-Bacterial Agents↗
PubMed1998

In vitro activity of cefepime and other broad-spectrum beta-lactams tested against 129 mec A-negative Staphylococcus spp. isolates: a multicenter sample.

The in vitro activity of cefepime was compared to that of penicillin, piperacillin/tazobactam, ceftazidime, ceftriaxone, imipenem, vancomycin, and teicoplanin by using the broth microdilution method against 129 isolates of Staphylococcus [50 S. aureus and 79 coagulase-negative staphylococci (CoNS], selected for their lack of the mec A gene as determined by the polymerase chain reaction. These isolates were obtained from a recent (1995-1996) surveillance of nearly 5000 nosocomial blood stream isolates from more than 40 geographically diverse U.S. medical centers. These results were compared to CoNS results from the same collection selected for their phenotypic susceptibility to oxacillin (OS; MIC < or = 2 micrograms/ml) regardless of their med A genotype. Cefepime, as well as piperacillin/ tazobactam, ceftriaxone, and imipenem, showed 100% susceptibility against OS and mec A-negative staphylococci. Ceftazidime showed relative resistance (30.2% resistant) against CoNS classified as OS based on phenotypic characteristics (MIC < or = 2 micrograms/mL) as compared to strains of mec A-negative CoNS (5.1% resistant). Accurate phenotypic detection of mec A-positive staphylococci by simple standardized in vitro susceptibility tests becomes very important to guide empirical use of beta-lactams for therapy. Furthermore, previously published MIC90 and range data for broad-spectrum beta-lactams versus OS have been falsely elevated by the presence of mec A-positive strains. The greater use of these potent beta-lactams against true mec A-negative staphylococci should enhance clinical outcomes and reduce the need for vancomycin.

Anti-Bacterial Agents↗
PubMed1998

National surveillance of nosocomial blood stream infection due to species of Candida other than Candida albicans: frequency of occurrence and antifungal susceptibility in the SCOPE Program. SCOPE Participant Group. Surveillance and Control of Pathogens of Epidemiologic.

A national surveillance program of nosocomial blood stream infections (BSI) in the USA between April 1995 and June 1996 revealed that Candida was the fourth leading cause of nosocomial BSI, accounting for 8% of all infections. Forty-eight percent of 379 episodes of candidemia were due to species other than Candida albicans. The rank order of non-C. albicans species was C. glabrata (20%) > C. tropicalis (11%) > C. parapsilosis (8%) > C. krusei (5%) > other Candida spp. (4%). The species distribution varied according to geographic region, with non-C. albicans species predominating in the Northeast (54%) and Southeast (53%) regions, and C. albicans predominating in the Northwest (60%) and Southwest (70%) regions. In vitro susceptibility studies demonstrated that 95% of non-C. albicans isolates were susceptible to 5-fluorocytosine, and 84% and 75% were susceptible to fluconazole and itraconazole, respectively. Geographic variation in susceptibility to itraconazole, but not other agents, was observed. Isolates from the Northwest and Southeast regions were more frequently resistant to itraconazole (29-30%) than those from the Northeast and Southwest regions (17-18%). Molecular epidemiologic studies revealed possible nosocomial transmission (five medical centers). Continued surveillance for the presence of non-C. albicans species among hospitalized patients is recommended.

Antifungal Agents↗
PubMed1998

Staphylococcus aureus and coagulase-negative staphylococci from blood stream infections: frequency of occurrence, antimicrobial susceptibility, and molecular (mecA) characterization of oxacillin resistance in the SCOPE program.

Staphylococci are major causes of nosocomial blood stream infection. The recently completed SCOPE Surveillance Program found that coagulase-negative staphylococci (CoNS) and Staphylococcus aureus were the first and second most common etiologic agents, respectively, causing nosocomial blood stream infection in the USA. The frequency of oxacillin resistance was 68% among 1553 strains of CoNS and 26% among 787 strains of S. aureus in this study. Extended susceptibility profiles were generated for a subset of 150 S. aureus and 300 CoNS against 16 antimicrobial agents. Oxacillin-susceptible strains of both CoNS and S. aureus were uniformly susceptible to beta-lactam agents with the exception of ampicillin and penicillin. Oxacillin-susceptible S. aureus were also highly susceptible to the fluoroquinolones, aminoglycosides, and trimethoprim/sulfamethoxazole. The oxacillin-susceptible CoNS were less susceptible to these agents, and only glycopeptides were reliably active against oxacillin-resistant strains. PCR detection of the mecA gene was used to scrutinize current NCCLS interpretive breakpoint MICs for determining susceptibility or resistance to oxacillin. We found complete concordance between the presence or absence of mecA and the NCCLS oxacillin interpretive breakpoint categories for S. aureus. In contrast, the NCCLS breakpoints for oxacillin significantly underestimate the degree of true oxacillin resistance among CoNS. Using the presence of mecA as the reference standard, we detected 15.7% false susceptibility to oxacillin using a MIC susceptible breakpoint concentration of < or = 2 micrograms/mL. Lowering the oxacillin MIC breakpoint to < or = 0.25 microgram/mL for CoNS would greatly improve the accuracy of the MIC test performance. We found that both the current oxacillin disk test and the 30-microgram ceftizoxime disk test functioned quite well in predicting those strains of CoNS that contain mecA. These studies have demonstrated both a high level of antimicrobial resistance among nosocomial blood stream isolates of staphylococci as well as significant problems with the current NCCLS breakpoints for oxacillin when testing CoNS.

Anti-Bacterial Agents↗
PubMed1998

Antimicrobial activity and spectrum investigation of eight broad-spectrum beta-lactam drugs: a 1997 surveillance trial in 102 medical centers in the United States. Cefepime Study Group.

Because antimicrobial agents become less effective after the emergence of resistance mechanisms in clinically prevalent pathogens, physicians must utilize local, regional, and national antimicrobial susceptibility surveillance data to assist in choices of appropriate agents. An investigation of the spectrum and potency of eight broad-spectrum beta-lactam drugs (cefepime, cefotaxime, ceftazidime, ceftriaxone, imipenem, piperacillin with or without tazobactam, and ticarcillin/clavulanic acid) was performed using a common protocol and method (Etest; AB BIODISK, Solna, Sweden) in 102 clinical microbiology laboratories in the United States. A total of 9777 strains of Gram-negative bacilli were tested from late 1996 through April 1997. Quality assurance measures using three control strains observed quality control failures in 13 laboratories (usually ticarcillin/clavulanic acid or piperacillin), but only 2% of results required deletion. A total of 33.4% of Enterobacter spp. (1977 strains) were either resistant or intermediately susceptible to ceftazidime. Only imipenem (99.6% susceptible) and cefepime (99.1%) remained highly active against strains of Enterobacter, as well as Citrobacter freundii, indole-positive Proteae, and Serratia spp. Ceftazidime-resistant Escherichia coli and Klebsiella pneumoniae were detected at rates of 10.3% and 23.8%, respectively. Although these were participant-selected strains, only imipenem and cefepime had broad-spectrum coverage (> or = 97.1%) against these extended-spectrum beta-lactamase phenotypes. A dominant number of these extended-spectrum beta-lactamase phenotypes were reported from medical centers in the Northeast, but a nationwide distribution was observed. Among the nonenteric Gram-negative bacilli (4057 strains), the rank order of susceptibility (percent inhibited at published breakpoint concentrations) was: imipenem (86.1%) > piperacillin/tazobactam (80.1%) > cefepime (77.1%) > ceftazidime = piperacillin (74.9%) > ticarcillin/clavulanic acid (61.6%) > cefotaxime (18.2%) > ceftriaxone (12.9%). The cephalosporins, cefepime and ceftazidime, had rates of resistance for the 3005 Pseudomonas aeruginosa isolates of 10.1% and 14.4%, respectively. For all Gram-negative strains tested, only two contemporary beta-lactam antimicrobials exhibited > 90% inhibition of strains, imipenem at 93.6% and cefepime at 90.2%. These drugs were superior to the other tested compounds (48.8-84.3%). Ticarcillin/clavulanic acid had the narrowest spectrum of activity (48.8% of isolates susceptible). These results indicate that carbapenems and a new fourth-generation cephalosporin, cefepime, possess usable in vitro potencies against current clinical strains of Gram-negative bacilli, many of which harbored resistance to other antimicrobial agents.

Anti-Bacterial Agents↗
PubMed1998

National surveillance of nosocomial blood stream infection due to Candida albicans: frequency of occurrence and antifungal susceptibility in the SCOPE Program.

Surveillance of nosocomial blood stream infections (BSI) in the USA between April 1995 and June 1996 revealed that Candida was the fourth leading cause of nosocomial BSI, accounting for 8% of all infections. Fifty-two percent of 379 episodes of candidemia were due to Candida albicans. In vitro susceptibility studies using the 1997 National Committee for Clinical Laboratory Standards reference method demonstrated that 92% of C. albicans isolates were susceptible to 5-fluorocytosine and 90% were susceptible to fluconazole and itraconazole. Geographic variation in susceptibility of fluconazole and itraconazole was observed. Isolates from the Northwest and Southeast regions were more frequently resistant to fluconazole (13.3-15.5%) and to itraconazole (17.2-20.0%) than those from the Northeast and Southwest regions (2.9-5.5% resistant to fluconazole and itraconazole). Continued surveillance for infections caused by C. albicans and other species of Candida among hospitalized patients is recommended.

Antifungal Agents↗
PubMed1998

In vitro activity of two echinocandin derivatives, LY303366 and MK-0991 (L-743,792), against clinical isolates of Aspergillus, Fusarium, Rhizopus, and other filamentous fungi.

LY303366 and MK-0991 (previously L-743,792) are new echinocandin derivatives with excellent broad-spectrum antifungal activity. We investigated the in vitro activity of LY303366, MK-0991, itraconazole, amnphotericin B, and 5-flucytosine against 51 clinical isolates of filamentous fungi, including Aspergillus flavus (10), A. fumigatus (12), Fusarium spp. (13), Rhizopus spp. (6), Pseudallescheria boydii (5), and one isolate each of Acremonium spp., A. niger, A terreus, Paecilomyces spp., and Trichoderma spp. In vitro susceptibility testing was performed using a microdilution broth method performed according to National Committee for Clinical Laboratory Standards guidelines. Ly303366 was two- to fourfold more active than MK-0991 against A. flavus, A. fumigatus, and Trichoderma spp. Both LY303366 and MK-0991 were considerably more active (MIC90 of 0.03-0.12 micrograms/mL) than itraconazole, amphotericin B, and 5-flucytosine against Aspergillus spp., but were less active than intraconazole and amphotericin B against Rhizopus spp. MK-0991 was more active than either LY303366 or intraconazole against Acremonium spp., Paecilomyces spp., and P. boydii. These data demonstrate promising activity of both LY303366 and MK-0991 against Aspergillus spp. and other species of filamentous fungi that are likely to be encountered clinically. Further in vitro and in vivo investigation is indicated.

Anidulafungin↗
PubMed1998

In vitro evaluation of sparfloxacin activity and spectrum against 24,940 pathogens isolated in the United States and Canada, the final analysis.

Sparfloxacin, a recently marketed oral fluoroquinolone, was tested against 24,940 recent clinical strains isolated from blood stream and respiratory tract cultures at 187 hospitals in the USA and Canada. Sparfloxacin activity was compared with 5 to 13 antimicrobial agents using either Etest (AB BIODISK, Solna, Sweden) and a reference broth microdilution or a standardized disk diffusion method. When applying recommended MIC breakpoint criteria of sparfloxacin susceptibility (< or = 0.5 microgram/mL) for Streptococcus pneumoniae (4,410 strains) and other Streptococcus spp. (554 isolates), 93% and 88% were inhibited, respectively. Furthermore, at < or = 1 microgram/mL sparfloxacin susceptibility rates for streptococci increased to 98% overall and 99.3% for S. pneumoniae. In contrast, only 46% and 68% of pneumococci were susceptible to ciprofloxacin (MIC90, 3 micrograms/mL; susceptible at < or = 1 microgram/mL) and penicillin (MIC90, 1.5 microgram/mL; susceptible at < or = 0.06 microgram/mL), respectively. Differences between regions in the USA for rates of penicillin-resistant pneumococcal strains were observed (greatest resistances in southeast and midwest), but results indicate that the sparfloxacin potency was not adversely influenced (MIC90, 0.5 microgram/mL). Also pneumococcal isolates from the lower respiratory tract were more resistant to penicillin and other beta-lactams. Nearly all Haemophilus species and Moraxella catarrhalis strains, including those harboring beta-lactamases, were susceptible to tested fluoroquinolones (sparfloxacin, ciprofloxacin), amoxicillin/clavulanic acid, and newer oral cephalosporins. Sparfloxacin was very active against oxacillin-susceptible Staphylococcus aureus (MIC90, 0.12 microgram/mL; 96-97% susceptible), Klebsiella spp. (MIC90 0.12 microgram/mL), and other tested enteric bacilli (92-95% susceptible). Comparisons between the broth microdilution MIC and disk diffusion interpretive results demonstrated excellent intermethod susceptibility category agreement (> 95%) using current sparfloxacin breakpoints, but some compounds (cefpodoxime disk diffusion tests for S. aureus) may require modifications. These results demonstrate that new Gram-positive focused fluoroquinolones (sparfloxacin) possess an excellent in vitro activity and spectrum against pathogens that cause respiratory tract infections. This spectrum of activity includes strains resistant to other antimicrobial classes, including the oral cephalosporins, macrolides, amoxicillin/clavulanic acid, and earlier fluoroquinolones (ciprofloxacin, ofloxacin). Overall, sparfloxacin inhibited 89% to nearly 100% of the isolates (species variable) tested against those species against which it has Food and Drug Administration indications for clinical use.

Anti-Infective Agents↗
PubMed1998

Combinations of orally administered beta-lactams to maximize spectrum and activity against drug-resistant respiratory tract pathogens: I. Synergy studies of amoxicillin and cefixime with Streptococcus pneumoniae.

Streptococcus pneumoniae strains have emerged that are resistant to penicillin (MICs >0.06 microg/mL) and many other beta-lactams. However, some older compounds such as amoxicillin have potency against these pneumococci with altered penicillin-binding proteins, but are labile to beta-lactamases produced by other prevalent respiratory tract pathogens. The interactions of amoxicillin with an enzyme-stable cephalosporin (cefixime) with a long elimination half-life were examined by the checkerboard dilution method versus 39 S. pneumoniae strains (13 resistant, 15 intermediate, and 11 susceptible to penicillin). Among 24 strains with evaluable drug interaction tests, 17 (71%) demonstrated partial or complete synergy. This favorable interaction produces a cefixime susceptibility category change from resistant or intermediate to susceptible for 16 of 28 strains (57%), when combined with < or = 1 microg/mL amoxicillin. Thus, the use of two currently available oral beta-lactams (amoxicillin twice a day + cefixime once a day; three total doses) appears to be a potential alternative treatment with greater spectrum for community-acquired respiratory tract infections pending clinical trial results.

Administration, Oral↗
PubMed1998

Comparative antimicrobial activity and kill-curve investigations of novel ketolide antimicrobial agents (HMR 3004 and HMR 3647) tested against Haemophilus influenzae and Moraxella catarrhalis strains.

The activity of two ketolide compounds, HMR 3004 and 3647, were compared to those of five macrolides, quinupristin/dalfopristin, ciprofloxacin, and ampicillin. The rate of killing for the ketolides was also assessed against Haemophilus influenzae and Moraxella catarrhalis. One hundred H. influenzae and 148 M. catarrhalis isolates were tested using broth microdilution and appropriate growth media. The killing rates of HMR 3004 and 3647 were analyzed using the time-kill method against five strains from each of the two species. Against H. influenzae, the activity of the ketolides (MIC90, 2 or 4 microg/mL) resembled that of azithromycin and quinupristin/dalfopristin and was more active than any tested macrolide. Against M. catarrhalis, HMR 3004 and 3647 were equally potent as azithromycin and clarithromycin (MIC50, 0.06 microg/mL and MIC90, 0.12 microg/mL) and more potent than all other macrolides or quinupristin/dalfopristin. Time-kill kinetic studies revealed that like the macrolide compounds, the ketolides are bacteristatic at or near the MIC for both H. influenzae and M. catarrhalis. This activity can be increased to a bactericidal level if the concentration is increased four- or eightfold the MIC for H. influenzae. In conclusion, HMR 3004 and 3647 have bacteristatic activity against tested respiratory pathogens and may prove to have an important role against macrolide-resistant isolates.

Anti-Bacterial Agents↗
PubMed1998

Important and emerging beta-lactamase-mediated resistances in hospital-based pathogens: the Amp C enzymes.

Resistance to third-generation cephalosporins mediated by beta-lactamases is an increasing problem for clinical therapeutics. A wide range of Enterobacteriaceae produce these AmpC enzymes (Bush-Jacoby-Medeiros group 1), including Enterobacter spp., Citrobacter freundii, Morganella morganii, Providencia spp., and Serratia marcescens. Resistance via this mechanism has been shown to be statistically correlated with the use of some third-generation cephalosporins, and the infections caused by these stably derepressed enzyme-producing species seem to occur most frequently in the seriously ill. More recently the genes encoding this enzyme have been documented on plasmids capable of transfer into other species such as Klebsiella pneumoniae. Fourth-generation cephalosporins, with stability and low affinity for the Amp C beta-lactamases and the ability to penetrate rapidly into the periplasmic space of Gram-negative organisms, offer a viable alternative in the treatment of these infections or as empiric regimens. Furthermore, these compounds (example: cefpirome) possess greater potency against the frequently occurring Gram-positive cocci such as oxacillin-susceptible staphylococci and the streptococci (including some penicillin-resistant strains) as compared to previously used anti-pseudomonal cephalosporias, ceftazidime.

Bacterial Proteins↗
PubMed1998

Bacterial resistance: a worldwide problem.

The therapeutic crisis produced by emerging antimicrobial resistances has compromised the chemotherapy of hospitalized patients with serious infections. For the most prevalent resistance problems, meropenem, a new carbapenem, appears to provide a potency and spectrum for: 1) extended-spectrum beta-lactamase-producing Enterobacteriaceae; 2) Bush-Jacoby-Merdeiros group 1 enzyme-producing ceftazidime-resistant Enterobacter spp., Citrobacter freundii, and some Serratia spp.; 3) ceftazidime- and imipenem-resistant Pseudomonas aeruginosa; and 4) some Streptococcus spp. with elevated penicillin MICs. Documented in vitro study results using 1997 gram-negative blood stream infection isolates indicate a wider spectrum and a two- to fourfold greater potency for meropenem compared with imipenem. This was especially true for P. aeruginosa where 93.4% of strains were susceptible to meropenem (84.1% for imipenem). Also among over 30,000 reported in vitro meropenem results from the United States and Europe, 90.6% of gram-positive cocci and 99.1% of anaerobes were inhibited at < or = 4 microg/ml. Over 90% of ceftazidime-resistant blood stream infection strains were meropenem susceptible, a rate greater than those of imipenem, ciprofloxacin, and gentamicin. As the clinical utility of many contemporary antimicrobial agents is challenged by emerging resistance, the carbapenems (meropenem, imipenem) appear positioned for a greater role in the treatment of infections in hospitalized patients.

Bacteria↗