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[Which betalactam antibiotic use as a marker of multiresistance in Pseudomonas aeruginosa?].

The determination of an indicating antibiotic for multiresistance, as methicillin in staphylococci, can be useful for Pseudomonas aeruginosa. Until now, the majority of the hygienists used ticarcillin, ceftazidim or imipenem in their investigations as markers of multiresistance for this species. Piperacillin has never been proposed for this purpose. To evaluate this choice, 2098 non-repetitive P. aeruginosa strains collected from 15 teaching hospitals in 1997-1999 were analysed, for eight antibiotics (ticarcillin, piperacillin, ceftazidim, imipenem, tobramycin, amikacin, ciprofloxacin, fosfomycin) according (i) to the results of the minimal inhibiting concentrations obtained by dilution in Mueller-Hinton agar, (ii) to their susceptibility following the criteria of Comité de l'antibiogramme de la Société Française de Microbiologie and (iii) to the determination of the mechanisms of resistance to the beta-lactam antibiotics. The low rates of sensitivity to the beta-lactam antibiotics, aminoglycosides, ciprofloxacin and fosfomycin were more frequent for piperacillin-resistant strains than for ceftazidim-resistant ones. Resistance to the other beta-lactam antibiotics are poor markers of multiresistance. In the light of the presented data, piperacillin seems to be, among the beta-lactam antibiotics, the best candidate as a marker of multiresistance for P. aeruginosa, followed by ceftazidim. This multiresistance is mainly found in strains overproducing AmpC cephalosporinase or transferable beta-lactamases. These mechanisms are well detected by resistance to piperacillin.

Anti-Bacterial Agents↗

Evaluation of the in vitro activity of six broad-spectrum beta-lactam antimicrobial agents tested against over 2,000 clinical isolates from 22 medical centers in Japan. Japan Antimicrobial Resistance Study Group.

Numerous broad-spectrum beta-lactam antimicrobial agents have been introduced into medical practice since 1985. Although several of these compounds have advanced, infectious disease therapy resistances to them has also emerged world-wide. In 1997, a Japanese 22 medical center investigation was initiated to assess the continued utility of these agents (oxacillin or piperacillin, ceftazidime, cefepime, cefpirome, cefoperazone/sulbactam [C/S], imipenem). The participating medical centers represented a wide geographic distribution, and a common protocol and reagents were applied. Three control strains and a set of challenge organisms were provided to participant centers. Etest (AB BIODISK, Solna, Sweden) strips were used in concurrent tests of these organisms and a qualitative determination of participant skills in the identification of resistant and susceptible phenotypes was established. The quantitative controls demonstrated 97.7-99.2% of MIC values within established QC limits, and the qualitative (susceptibility category) controls documented a 97.3% agreement of participant results with that of reference values (1,320 total results). Only 0.2% of values were false-susceptible errors. After the participant quality was assured, a total of 2,015 clinical strains were tested (10 strains from 10 different organism groups including methicillin-susceptible Staphylococcus aureus and coagulase-negative staphylococci [CoNS], Escherichia coli, Klebsiella spp., Citrobacter freundii, Enterobacter spp., indole-positive Proteae, Serratia spp., Acinetobacter spp., and Pseudomonas aeruginosa). The staphylococci were uniformly susceptible to all drugs tested except ceftazidime (MIC90, 24 micrograms/ml) that had a potency six- to 12-fold less than either cefepime or cefpirome. Only 3.7 and 45.1% of S. aureus and CoNS were susceptible to ceftazidime, respectively. Among E. coli and Klebsiella spp. the rank order of antimicrobial spectrum was imipenem = "fourth-generation" cephalosporins > ceftazidime > C/S > piperacillin. Possible extended spectrum beta-lactamase phenotypes were identified in 2.9-8.6% of these isolates. Isolates of C. freundii, Enterobacter spp., Proteae, and Serratia spp. that were resistant to ceftazidime and piperacillin remained susceptible to imipenem (0.0-4.5% resistance) and cefepime (0.0-5.0%). Acinetobacters were inhibited best by C/S (99.5% susceptible) and least susceptible to piperacillin (MIC90, > 256 micrograms/ml; 21.7% susceptible) activity. P. aeruginosa isolates were most susceptible to cefepime (83.6%) and this zwitterionic cephalosporin also had the lowest level of resistance (9.1% of MICs at > or = 32 micrograms/ml). Several multi-resistant organisms were identified in participant medical centers including S. marcescens strains resistant to cefepime, imipenem, or both observed in six hospitals. Clonal spread was documented in two medical centers; one hospital having two distinct epidemic clusters. Also a multi-resistant E. cloacae was found in two patients in the same hospital. Evaluations of carbapenem resistance in four species discovered only two strains (in same hospital) among 40 P. aeruginosa isolates (5.0%) with a metallo-enzyme, with nearly all of the remaining strains inhibited by an Ambler Class C enzyme inhibitor (BRL42715) indicating a hyperproduction of a chromosomal cephalosporinase. These results indicate that most newer beta-lactams remain widely useable in medical centers in Japan, but emerging often clonal, resistances have occurred. The overall rank order of antimicrobial spectrum against all ten tested bacterial groups favors the "fourth-generation" cephalosporin, cefepime (96.4% susceptible) as an equal to imipenem (95.9%) > C/S (90.9%) = cefpirome (90.0%) > ceftazidime (75.1%) = penicillins, either oxacillin or piperacillin (76.4%).

Anti-Bacterial Agents↗

Association of antibiotic utilization measures and control of multiple-drug resistance in Klebsiella pneumoniae.

OBJECTIVE: To study the association of antibiotic-utilization measures and control of multidrug-resistant (MDR) Klebsiella pneumoniae after emergence in two hospitals in our medical center. DESIGN AND SETTING: Rates of MDR K. pneumoniae at two hospitals were compared before and after acute interventions, including emphasis on Contact Precautions and education in antibiotic utilization. Antipseudomonal beta-lactam antibiotic use was measured before and after the interventions at both hospitals. Pulsed-field gel electrophoresis of whole cell DNA was used as a marker of strain identity. RESULTS: Clonal strain dissemination was the major mechanism of emergence at hospital A; emergence was polyclonal at hospital B. Antibiotic-utilization interventions at both institutions included physician education regarding the association of ceftazidime use and MDR K. pneumoniae. At hospital A, ceftazidime use decreased from 4,301 g in the preintervention period, to 1,248 g in the postintervention period. Piperacillin-tazobactam use increased from 12,455 g to 17,464 g. Ceftazidime resistance in K. pneumoniae decreased from 110 (22%) of 503 isolates to 61 (15%) of 407 isolates (P<.05); piperacillin-tazobactam resistance decreased from 181 (36%) of 503 to 77 (19%) of 407 isolates (P<.05). At hospital B, ceftazidime use decreased from 6,533 g in the preintervention period to 4,792 g in the postintervention period. Piperacillin-tazobactam use increased from 58,691 g to 67,027 g. Ceftazidime resistance in K. pneumoniae decreased from 42 (10%) of 415 isolates to 19 (5%) of 383 isolates (P<.05). Piperacillin-tazobactam resistance decreased from 91 (22%) of 415 isolates to 54 (14%) of 383 isolates (P<.05). Follow-up data showed continued decrease in piperacillin-tazobactam resistance despite increased use at both hospitals. CONCLUSIONS: Antibiotic-use measures may be particularly important for control of MDR K. pneumoniae, whether emergence is clonal or polyclonal.

Anti-Bacterial Agents↗

Resistance determinants for beta-lactam antibiotics in laboratory mutants of Streptococcus pneumoniae that are involved in genetic competence.

Laboratory mutants of Streptococcus pneumoniae resistant to either cefotaxime or piperacillin reveal defects in competence development independent of the selective beta-lactam. A resistance determinant ciaH encoding a putative histidine kinase of a two-component signal-transducing system that is also involved in competence regulation was recently identified in cefotaxime-resistant mutants. We show now that the CiaH protein can be phosphorylated by ATP in vitro, and that it also phosphorylates the cognate response regulator CiaR. The mutant C306 containing the CiaH mutation Thr-230-Pro is completely noncompetent. It does not release competence-inducing activity (competence factor) into the medium nor can such an activity be released from the cells. Competence in C306 cannot be induced upon addition of external competence factor, in contrast to the competence-defective piperacillin-resistant mutants P506 and P408. A novel resistance determinant cpoA specific for piperacillin was identified in piperacillin-resistant mutants. CpoA is responsible for the competence defect in P506 but not in P408. The results document a tight link between the action of beta-lactams and competence development in the pneumococcus and confirm that the two beta-lactams piperacillin and cefotaxime act via different primary targets.

Anti-Bacterial Agents↗

Comparative in vitro synergistic activity of new beta-lactam antimicrobial agents and amikacin against Pseudomonas aeruginosa and Serratia marcescens.

The in vitro synergistic activities of moxalactam, cefoperazone, or cefotaxime in combination with amikacin or piperacillin were compared against aminoglycoside-susceptible and aminoglycoside-resistant isolates of Pseudomonas aeruginosa and Serratia marcescens by the checkerboard agar dilution method. All antimicrobial combinations demonstrated some synergy, and no antagonism was observed. Moxalactam plus amikacin and piperacillin plus amikacin were most frequently synergistic (two-thirds of the isolates inhibited synergistically by each combination), whereas combinations of moxalactam, cefotaxime, or cefoperazone with piperacillin were synergistic against only 18 to 25% of the isolates. Moxalactam plus amikacin was the combination most often synergistic for amikacin-susceptible P. aeruginosa, and piperacillin plus amikacin was the combination most frequently synergistic for amikacin-resistant P. aeruginosa and amikacin-susceptible S. marcescens. These results demonstrate frequent in vitro synergistic activity between the new beta-lactam agents and amikacin (especially moxalactam or piperacillin with amikacin), but comparative clinical trials are needed to establish the relative efficacy and toxicity of these combinations.

Amikacin↗

Comparison of methodologies for synergism testing of drug combinations against resistant strains of Pseudomonas aeruginosa.

The purpose of this study was to determine if synergism was maintained for various combinations of beta-lactams with an aminoglycoside against four clinical strains and one laboratory strain of Pseudomonas aeruginosa which were resistant, according to the MICs, to the beta-lactams and/or aminoglycoside. The results from both the checkerboard and killing curve methodologies were compared. The laboratory strain (ATCC 27853) was manipulated in vitro by serial passage onto agar containing increasing concentrations of each antibiotic to select for resistance. One clinical isolate (R61) was also serially passed to raise the MIC of piperacillin from 128 to 1,024 micrograms/ml. The fractional inhibitory concentration indices for all isolates indicated indifference for all combination therapies, with values ranging from 0.6 to 3. In contrast, killing curve results for all isolates demonstrated synergism with drug concentrations at either one-fourth or one-half the MIC for each organism. The MIC of piperacillin for the laboratory-manipulated clinical isolate R61 was 1,024 micrograms/ml, and synergism was still observed with concentrations of one-half the MIC of piperacillin and amikacin. For clinical isolate R166, which was beta-lactam and tobramycin resistant, synergism continued to be demonstrated with concentrations of tobramycin (1/16 MIC) in combination with piperacillin and cefepime at 1/2 the MIC. The results of this study indicate that against P. aeruginosa, synergism is observed in spite of resistance to beta-lactams and/or aminoglycosides. Synergism appears to be maintained even at very high MICs (piperacillin, 1,024 micrograms/ml; tobramycin, 128 micrograms/ml) with drug concentrations within achievable therapeutic ranges. With current definitions of synergism there was a complete lack of correlation between the results obtained by the checkerboard and killing curve methodologies, with the fractional inhibitory concentration indices showing indifference and killing curves resulting in synergism. The methodologies and definitions of synergism or antagonism are variable and not standardized and should be reevaluated.

Aminoglycosides↗

In vitro activities of the beta-lactamase inhibitors clavulanic acid, sulbactam, and tazobactam alone or in combination with beta-lactams against epidemiologically characterized multidrug-resistant Acinetobacter baumannii strains.

Acinetobacter baumannii is an important nosocomial pathogen usually in the context of serious underlying disease. Multidrug resistance in these organisms is frequent. The beta-lactamase inhibitors clavulanic acid, sulbactam, and tazobactam have intrinsic activity against Acinetobacter strains. To evaluate their potential therapeutic usefulness, we determined the in vitro activity of ampicillin, sulbactam, ampicillin-sulbactam, cefoperazone, cefoperazone-sulbactam, piperacillin, piperacillin-sulbactam, tazobactam, piperacillin-tazobactam, amoxicillin, clavulanic acid, amoxicillin-clavulanic acid, ticarcillin, and ticarcillin-clavulanic acid against multidrug-resistant A. baumannii. All isolates were epidemiologically characterized by RAPD [random(ly) amplified polymorphic DNA] analysis and/or pulsed-field gel electrophoresis and represented different strain types, including sporadic strains, as well as outbreak-related strains. The MICs were determined by agar dilution on Mueller-Hinton agar (using fixed concentrations, as well as fixed ratios for beta-lactamase inhibitors) and the E-test. The majority of E-test results were within two dilutions of those recorded by agar dilution, with the exception of piperacillin-tazobactam. Sulbactam was superior to clavulanic acid and tazobactam and may represent an alternative treatment option for infections due to multiresistant A. baumannii strains. beta-Lactamase inhibitors have intrinsic activity but do not enhance activity of beta-lactams against A. baumannii. Testing with the inhibitor added at a fixed concentration as recommended for piperacillin-tazobactam and ticarcillin-clavulanic acid by the National Committee for Clinical Laboratory Standards may falsely suggest high activity or gives uninterpretable results due to trailing. If combinations are used for testing, fixed ratios may give more useful results.

Acinetobacter Infections↗

Wide variability in Pseudomonas aeruginosa aminoglycoside results among seven susceptibility testing procedures.

Seven commonly used antimicrobial susceptibility testing methods were used to test the susceptibility of 150 isolates of Pseudomonas aeruginosa against gentamicin, tobramycin, amikacin, carbenicillin, and piperacillin. Results were compared with respect to the susceptibility characteristics of the population of isolates as defined by each method. Conventional methods included agar disk diffusion and agar dilution, carried out in accordance with current recommendations of the National Committee for Clinical Laboratory Standards, as well as broth microdilution testing with cation-supplemented Mueller-Hinton broth (CSMHB). Methods in which instrumentation was used for result determination included the Autobac I, Avantage, Sensititre Autoreader (using a breakpoint panel at 18 h of incubation), and Vitek (AMS-240, using the GNS susceptibility card). When necessary for comparison, MIC data were converted to categorical interpretations (susceptible, intermediate, and resistant). With respect to gentamicin, no significant differences were noted among the results of disk diffusion, broth microdilution, Sensititre Auto breakpoint, or Vitek methods which characterized 60 to 67% of isolates as susceptible, 16 to 22% as intermediate, and 13 to 17% as resistant. In contrast, agar dilution, Autobac, and Avantage, although yielding gentamicin results similar to those of one another, were each significantly different in result reporting from the other four methods above for gentamicin results, and they characterized the Pseudomonas population largely as susceptible (88 to 97%), with 0 to 6% intermediate and only 3% to 6% resistant. More isolates were characterized as being resistant to gentamicin in the Avantage test if an assay broth supplemented with increased amounts of calcium was used. Cation impregnation of Autobac disks did not appreciably change Autobac results. The geometric mean MIC of gentamicin was 4 micrograms/ml lower in the agar dilution method than in the CSMHB microdilution method, despite monitoring of the agar for cation content through performance disk diffusion testing with P. aeruginosa ATCC 27853. Tobramycin activity was greater than gentamicin activity, and susceptibility to tobramycin ranged from 89 to 97%, with few statistically significant differences noted among the seven methods studied. Differences in MIC distribution and geometric mean MIC between agar dilution and CSMHB microdilution testing were minimal and suggested less of a cation influence on tobramycin than gentamicin results. Although amikacin was also more active than gentamicin (83 to 99% of isolates were susceptible), differences in the amikacin results among methods tended to reflect the same trends in reporting as seen with gentamicin testing, with the exception that results of Avantage testing were similar to those of disk diffusion, CSMHB microdilution, Sensititre, and Vitek. A difference in geometric mean MIC of 5 micrograms/ml between CSMHB testing and agar dilution testing suggested the influence of divalent cations on amikacin results. Few highly significant differences were noted among methods when isolates were tested against carbenicillin and piperacillin, except that Avantage piperacillin results (66% susceptible) and Autobac piperacillin results (98% susceptible) were noticeably different from the percent piperacillin susceptibility (range, 85 to 92%) measured by the other methods. Method-dependent variability among aminoglycoside susceptibility results, particularly when testing gentamicin, prevents meaningful comparison of Pseudomonas susceptibility trends among hospitals when different methods are used and promotes confusion and frustration among clinical microbiologists and clinicians owing to the uncertainties of clinical meaning of these data.

Aminoglycosides↗

Comparison of in vitro activities of eight new beta-lactam compounds against cephalothin-resistant Enterobacteriaceae from hospital patients.

The in vitro antibacterial activity of eight newer beta-lactam antibiotics (mecillinam, piperacillin, mezlocillin, cefoxitin, cefotaxime, moxalactam, ceftriaxone and ceftazidime) was determined against 87 cephalothin-resistant strains of Enterobacteriaceae isolated during 6 months in a general hospital. Ceftriaxone, cefotaxime, moxalactam and ceftazidime proved to be highly active; only a minority of strains required higher concentrations than 0.125 microgram/ml for inhibition of growth. Cefoxitin, mecillinam, mezlocillin and piperacillin were less active. Mecillinam displayed greater efficacy against Escherichia coli, Klebsiella and Enterobacter spp., while the same was the case for piperacillin against Proteus mirabilis and Serratia marcescens, and for cefoxitin against indole-positive Proteus spp. The production of beta-lactamase was correlated with a reduced activity of mecillinam, mezlocillin and piperacillin but not of cefoxitin or the other beta-lactamase-stable cephalosporins. However, some strains, mainly those of Proteus, Enterobacter and Serratia, though resistant to mecillinam, mezlocillin and piperacillin did not produce beta-lactamases. This observation might indicate that ceftriaxone, moxalactam, cefotaxime and ceftazidime, besides their indifference to beta-lactamases, are characterized also by a high degree of intrinsic activity.

Anti-Bacterial Agents↗

The effect of an antimicrobial restriction program on Pseudomonas aeruginosa resistance to beta-lactams in a large teaching hospital.

STUDY OBJECTIVES: To compare the use of beta-lactams and subsequent Pseudomonas aeruginosa sensitivity patterns before and after implementation of a clinical pharmacist-facilitated antimicrobial restriction program in August 1997. DESIGN: Retrospective consecutive data collection. SETTING: Large university-affiliated medical center. INTERVENTION: The study results are the accumulation of the daily intervention activities of the antimicrobial restriction program. Data on antimicrobial grams purchased/1,000 patient-days and susceptibility patterns were collected and analyzed retrospectively. MEASURES AND MAIN RESULTS: Annual grams of ceftazidime, piperacillin, piperacillin-tazobactam, and other antipseudomonal beta-lactams purchased/1,000 patient-days were compared during the 2 full calendar years before the antimicrobial restriction program (1995-1996) with the 4 full calendar years after the program was implemented (1998-2001). Pseudomonas aeruginosa resistance trends for the antipseudomonal beta-lactams, ciprofloxacin, and tobramycin also were compared for the 2 years before the program (1995-1996) with the last 2 years of the program (2000-2001). A 44% reduction in ceftazidime use was documented; ostensibly, minimal changes occurred in the overall use of piperacillin and piperacillin-tazobactam. During the same time period, ceftazidime resistance fell from 24% to 11.8% (p<0.001), whereas piperacillin resistance fell from 32.5% to 18.5% (p<0.001). Imipenem resistance declined from 20.5% to 12.3% (p<0.001) with an 18% reduction in use. Aztreonam resistance declined from 29.5% to 16.5% (p<0.001) despite a 57% increase in use. No changes in resistance to either ciprofloxacin or tobramycin were found. CONCLUSION: Through an antimicrobial restriction program, a dramatic reduction in ceftazidime use was achieved with judicious use of other antipseudomonal antimicrobials, which resulted in reduced resistance of P aeruginosa to other beta-lactams.

Anti-Bacterial Agents↗

["In vitro" activity of ten antimicrobial agents against anaerobic bacteria. A collaborative study, 1999-2002].

The antimicrobial activity of ampicillin, ampicillin-sulbactam, cefoxitin, ceftriaxone, imipenem, piperacillin, piperacillin-tazobactam, clindamycin, metronidazole, and azitromycin was assesed against 166 strains of anaerobic bacteria recovered from eight hospitals in Buenos Aires. The strains studied were Bacteroides fragilis group (65), Fusobacterium spp. (26), Prevotella spp. (21), Porphyromonas spp. (10), Clostridium difficile (10), other clostridia (12), and gram-positive cocci (22). The MICs were determined by the agar dilution method according to NCCLS document M11-A5. Metronidazole and piperacillin-tazobactam were the most active antimicrobial agents tested and exhibited MIC90 values of < or = 2 microg/ml and < or = 4 microg/ml against gram-negative organisms, and < or = 2 microg/ml, and < or = 8 microg/ml against gram-positive organisms, respectively. Among beta-lactams the activity against gram-negative rods was in the following order: imipenem > piperacillin > cefoxitin > ceftriaxone > ampicillin. Among the gram-positive bacteria the decreased activity was: piperacillin > imipenem > cefoxitin > ceftriaxone > ampicillin. The majority of the species studied showed different degrees of resistance to clindamycin and azitromycin. Nevertheless, 90% of Fusobacterium nucleatum and Porphyromonas spp. isolates were inhibited by 0.125 mg/ml of clindamycin and azitromycin, respectively.

Anti-Bacterial Agents↗

In vitro and in vivo activity of various antibiotics against Listeria monocytogenes type 4b.

Inadequate guidelines for the treatment of neonatal listeriosis led us to evaluate various antibiotics in a newborn rat model of Listeria monocytogenes type 4b sepsis. Minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC based on 99.9% killing), expressed as micrograms/ml, were determined for: ampicillin (MIC 0.46/MBC 3.20); ampicillin with subinhibitory concentrations of gentamicin (0.24/not done); erythromycin (0.14/3.59); gentamicin (0.38/1.11); gentamicin with subinhibitory concentrations of ampicillin (0.235/ND); piperacillin (2.7/16.8); rifampin (0.026/0.094); sulfamethoxazole (SMZ 47.5/ND); SMZ with subinhibitory concentrations of trimethoprim (0.74/1.48); trimethoprim (TMP 0.12/ND); and TMP with subinhibitory concentrations of SMZ (0.04/0.08). In the in vivo model, rats were challenged intraperitoneally with 2 X 10(6) cfu of L. monocytogenes at 3 days-of-age. Antibiotics (ampicillin, ampicillin + gentamicin, erythromycin, piperacillin or TMP/SMZ) were given every 12 h for 2 days starting on day 5 of life while rifampin was given once daily for 2 days. Survival tabulations and spleen cultures were done on day 8 of life. All animals who received antibiotics had better survival than the controls given saline (p less than 0.01 for rifampin, erythromycin, TMP/SMZ, ampicillin, ampicillin + gentamicin; p less than 0.05 for piperacillin). Rifampin, erythromycin and TMP/SMZ gave better survival than piperacillin (p less than 0.01). Although ampicillin plus gentamicin were superior to ampicillin alone (p less than 0.01) in reducing the number of organisms in the spleens, rifampin was superior to all regimens in this regard (p less than 0.0005 vs piperacillin, ampicillin, TMP/SMZ; p less than 0.05 vs ampicillin + gentamicin, erythromycin). Rifampin may be a useful addition to other regimens in speeding the elimination of the organism.

Animals↗

In vitro antienterococcal activity explains associations between exposures to antimicrobial agents and risk of colonization by multiresistant enterococci.

We compared ceftriaxone and piperacillin-tazobactam at doses ranging from 0.1 to 2 times the human equivalent daily dose (HEDD), to determine their impact on gastrointestinal colonization by ampicillin- and vancomycin-resistant Enterococcus faecium C68 in a mouse model. Ceftriaxone failed to promote colonization at doses up to 0.25 times the HEDD, whereas piperacillin-tazobactam promoted colonization at doses up to 0.5 times the HEDD. Ceftriaxone promoted colonization at doses at least 0.5 times the HEDD, whereas piperacillin-tazobactam inhibited colonization at doses at least 0.75 times the HEDD. Both piperacillin-tazobactam and ceftriaxone inhibited colonization by an enterococcal strain devoid of low-affinity penicillin-binding protein-5 (significantly increasing its susceptibility to these agents), at doses that promoted colonization by E. faecium C68. These results support a model in which the impact that different beta -lactam agents have on colonization by VRE is related to the level of the beta -lactam agent's intrinsic antienterococcal activity against the colonizing strain.

Animals↗

Reappraisal of the antimicrobial susceptibilities of Chryseobacterium and Flavobacterium species and methods for reliable susceptibility testing.

Several Flavobacterium species, comprising a heterogeneous group of gram-negative bacilli that are capable of causing opportunistic infections in humans, have recently been reclassified as Chryseobacterium or Myroides species. Intrinsically resistant to a number of antibiotics, these organisms have been reported to be susceptible to vancomycin and certain other drugs that are normally active against gram-positive bacteria. By using the National Committee for Clinical Laboratory Standards (NCCLS) broth microdilution procedure, 58 clinical isolates of former flavobacteria (36 Chryseobacterium meningosepticum isolates, 11 C. indologenes isolates, 3 C. gleum isolates, 4 unspeciated former members of Flavobacterium group IIb, and 4 Myroides odoratum isolates) were tested with 23 antibiotics, including conventional and investigational agents. In addition, the broth microdilution results were compared to those generated by agar dilution, E-test, and disk diffusion for vancomycin and piperacillin-tazobactam. Compared to the NCCLS microdilution results, there were 7.1 and 17.9% very major errors with piperacillin-tazobactam by agar dilution and E-test, respectively. In addition, there were from 12.1 to 48.3% minor errors with both procedures with vancomycin and piperacillin-tazobactam. The very major and minor error rates were unacceptably high with disk testing of piperacillin-tazobactam; the use of enterococcal vancomycin disk breakpoints (zone diameter of > or =17 mm = susceptible) resulted in >20% minor errors but only one very major error. All of the isolates were susceptible to minocycline; over 90% were susceptible to sparfloxacin, levofloxacin, and clinafloxacin; and 88% were susceptible to rifampin. None was susceptible to vancomycin. When Chryseobacterium or Myroides species are isolated from serious infections, susceptibility testing by broth microdilution should be performed and therapy should be guided by those results.

Anti-Bacterial Agents↗

Antimicrobial susceptibility of aerobic microorganisms isolated from intraabdominal infections in pediatric patients in Poland.

BACKGROUND: Growing resistance to antibiotics among both community-acquired and hospital pathogens is making the treatment of most infections increasingly difficult. Therefore, the aim of our multi-center study was to determine the antimicrobial susceptibility of the most frequent aerobic microorganisms isolated from children with intraabdominal infections. MATERIAL/METHODS: Bacterial pathogens were isolated from 256 consecutive patients treated in five large specialized hospitals in Poland from January 2001 to February 2002. Minimal inhibitory concentrations (MICs) of piperacillin, piperacillin-tazobactam, cefotaxime, ceftazidime and cefepime were determined by Etests. The production of extended spectrum beta-lactamases (ESBL) was detected by a double-disk test. RESULTS: Piperacillin-tazobactam was the most active agent against Enterobacteriaceae and Pseudomonas aeruginosa, inhibiting 92% and 78% of isolates respectively. Susceptibility of Enterobacteriaceae to cefotaxime, ceftazidime and cefepime was 73%, 73% and 87% respectively, and susceptibility of P. aeruginosa to both ceftazidime and cefepime was 76%. Extended-spectrum beta-lactamases were detected in 56% Klebsiella sp. and 11.5% E. coli, but the vast majority of these isolates remained susceptible to piperacillin-tazobactam (MIC(90) = 12 mg/L and MIC(90) = 1 mg/L, respectively). CONCLUSIONS: Piperacillin/tazobactam remains a valuable therapeutic option in Polish pediatric patients with intraabdominal infections, due to its good activity against ESbetaL-producing organisms and P. aeruginosa.

Abdomen↗

Piperacillin/tazobactam in comparison with clindamycin plus gentamicin in the treatment of intra-abdominal infections.

BACKGROUND: Concerned about the inactivation of piperacillin by beta-lactamase and the risk of aminoglycoside-induced nephrotoxicity and clindamycin-induced enterocolitis, we conducted the following phase III clinical trial. METHODS: Between November 1991 and March 1993, 77 surgical patients with intraabdominal infections were enrolled and randomly assigned in a 3:2 ratio to receive either piperacillin/tazobactam or clindamycin plus gentamicin to compare safety, tolerance and efficacy between both two treatment groups. RESULTS: There were 76 clinically and 50 bacteriologically evaluable patients with 80 isolated pathogens. The demographic data were comparable in both groups. There was no statistically significant difference of clinical response at any time-point of treatment, with 97.8% favorable clinical response rate in piperacillin tazobactam group and 96.6% in clindamycin plus gentamicin group at endpoint. The bacteriological eradication rates were similar, with 97.7% in piperacillin/tazobactam group and 94.4% in clindamycin plus gentamicin group at pathogen level, and 96.7% in piperacillin/tazobactam group and 95.0% in clindamycin plus gentamicin group at patient level. By susceptibility tests, only 3 (4%) isolated pathogens were resistant to piperacillin/tazobactam, which was much superior to the use of piperacillin, clindamycin or gentamicin alone in antimicrobial activity. The piperacillin tazobactam-related adverse experiences included 1 (2.1%) urticaria and 2 (4.3%) diarrhea. However, there were no significant differences in the adverse experiences between these two groups. CONCLUSIONS: This study has demonstrated that piperacillin/tazobactam is comparable with clindamycin plus gentamicin in efficacy, safety and tolerance in the treatment of surgical patients with intra-abdominal infections. The combination of piperacillin/tazobactam could potentially be the treatment of choice in adjunt to surgical management in intra-abdominal infection.

Abdomen↗

Randomized trial of beta-lactam regimens in febrile neutropenic cancer patients.

A three-arm prospective randomized trial was designed to compare the efficacies of piperacillin plus vancomycin, ceftazidime plus vancomycin, or all three drugs as initial therapy for fever in neutropenic cancer patients. The objectives were to determine whether a broad-spectrum penicillin was as effective as a broad-spectrum cephalosporin and whether two beta-lactam antibiotics were more effective than one. Four hundred and seventy of the 519 febrile episodes entered in the study could be evaluated for response. Ceftazidime plus vancomycin was significantly more effective than piperacillin plus vancomycin, considering all febrile episodes (79 percent versus 61 percent, p = 0.001), documented infections (79 percent versus 57 percent, p = 0.004), gram-negative infections (88 percent versus 47 percent, p = 0.001), and bacteremias (81 percent versus 51 percent, p = 0.01). The addition of piperacillin to ceftazidime (piperacillin plus ceftazidime and vancomycin versus ceftazidime plus vancomycin) did not improve the response rate and was associated with a significantly higher incidence of skin rash. Vancomycin plus ceftazidime provides adequate antibiotic coverage for initial treatment of fever in neutropenic patients. This combination was equally effective, less expensive, and less toxic than the double beta-lactam combination used in this study.

Adult↗

Comparative in vitro beta-lactam activity against aerobic and anaerobic surgical isolates.

The comparative in vitro activity of cefoxitin, piperacillin, cefotetan, and ceftizoxime was compared against 843 surgical microbial isolates. All compounds exhibited excellent activity against the streptococcal isolates. Antimicrobial activity was poor for Staphylococcus aureus and S. epidermidis. Cefotetan activity against the Enterobacteriaceae was comparable to ceftizoxime (greater than 95% susceptible). Resistance rates of 0, 1, 5, and 2% were observed with cefoxitin, piperacillin, cefotetan, and ceftizoxime against the anaerobic cocci and anaerobic gram-positive non-spore-forming rods. Ninety-six and ninety-nine percent of the clostridial strains were susceptible to cefotetan and piperacillin, respectively. Piperacillin, cefotetan, and ceftizoxime exhibited similar activity against Bacteroides fragilis (resistance less than 10%). Cefotetan and cefoxitin exhibited poor activity against Bacteroides distasonis, B. ovatus, and B. thetaiotaomicron. Antimicrobial activities were comparable for the four drugs against other Bacteroides and Fusobacterium species. The results demonstrate that all four compounds exhibited broad antimicrobial activity against facultative and obligate anaerobic surgical isolates from intraabdominal and soft tissue infections.

Abdomen↗