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Monobactam antibiotics in subinhibitory concentrations enhance opsonophagocytosis and serum bacteriolysis in certain Escherichia coli strains.

Capsular polysaccharides are known to protect Gram-negative bacteria from complement-mediated killing and opsonophagocytosis. Monobactam antibiotics selectively inhibit penicillin-binding protein 3 (PBP3), resulting in abnormally structured peptidoglycan, causing defective cell surface structures. The authors studied the influence of subinhibitory concentrations of the monobactam antibiotics aztreonam and carumonam on serum bacteriolysis and opsonophagocytosis of four K-encapsulated and five non-K-encapsulated Escherichia coli strains. It was observed that monobactam antibiotics in subinhibitory concentrations enhanced opsonophagocytosis of the four K-encapsulated and one non-K-encapsulated E. coli strains tested. Opsonophagocytosis of the other four non-K-encapsulated E. coli strains was not enhanced. Serum bacteriolysis studies revealed that of the four K-encapsulated strains tested only one strain showed a significant enhancement of bacteriolysis after treatment with subinhibitory concentrations of monobactam antibiotics. None of the unencapsulated strains showed a significant change in percentage lysis after treatment with either aztreonam or carumonam.

Anti-Bacterial Agents↗

[Comparative antibacterial activity of a new monobactam, carumonam (RO 17-2301, AMA 1080) on hospital bacteria resistant to beta lactams].

In vitro activity of a new monobactam, carumonam (RO 17-2301, AMA 1080) was tested against 370 hospital bacterial isolates. Results were compared to aztreonam, cefotaxime, cefmenoxime, latamoxef, ceftazidime, ceftriaxone, pefloxacin against Enterobacteriaceae, to aztreonam, piperacillin, cefoperazone, cefsulodin, ceftazidime, imipenem and pefloxacin against P. aeruginosa. All Enterobacteriaceae strains produced cephalosporinases and all P. aeruginosa strains were ticarcillin resistant. MIC 90% of carumonam against Enterobacteriaceae strains was lower than 0.25 mg/l for P. mirabilis, P. vulgaris, P. stuartii, Salmonella sp., ranged from 0.25 to 0.5 mg/l for Klebsiella sp. and S. marcescens, from 1 to 2 mg/l for E. coli and P. morganii, and from 4 to 8 mg/l for C. freundii and E. cloacae. The rate of strains inhibited with 4 mg/l of carumonam was 95.3%. So carumonam was at the second place from eight tested products, after latamoxef (97.5% of susceptible strains). Carumonam was active against second generation cephalosporins resistant strains when these strains were susceptible or intermediate to cefotaxime. Strains resistant to this compound escaped to its action. Its activity against A. calcoaceticus was weak (22.6% of strains inhibited by 4 mg/l), but was superior to that of cefsulodin against ticarcillin resistant P. aeruginosa strains (54.5 versus 16.1% of susceptible strains). However carumonam was less active against this last species than ceftazidime or imipenem (92.6 and 91% of susceptible strains respectively).

Anti-Bacterial Agents↗

New trends in paediatric antibiotic therapy.

Recently many new antibiotics have been marketed for use in paediatrics. Most of them offer no real advantage in comparison to older drugs and their prescription is questionable, particularly because they are highly expensive. Only a few have a number of special characteristics which permit in certain patients a significant improvement of antibiotic therapy. Among these there are some third-generation cephalosporins such as ceftazidime and cefsulodin, aztreonam and the new macrolides. Ceftazidime and cefsulodin are highly active, particularly against Pseudomonas spp., thus offering new therapeutic possibilities in life-threatening infections due to these bacteria. Aztreonam is the first monobactam and has a spectrum of activity limited to the aerobic Gram-negative bacilli. Its indications are therefore very similar to those of the aminoglycosides but its use seems to be safer because it has none of the important side-effects of those drugs. Alone or in combination, it may become the drug of choice to treat children with infection due to Gram-negative bacteria. New macrolides are active against erythromycin-resistant bacteria, have a lower risk of gastrointestinal side-effects and have no interference with concomitant administered drugs such as theophylline. Therefore they may be used with higher compliance and better efficacy, especially in the areas where erythromycin-resistant Gram-positive strains are increasingly evident.

Aminoglycosides↗

Comparative in vitro activity and beta-lactamase stability of CGP 31523A, a new aminothiazolyl cephalosporin.

The in vitro activity of CGP 31523A, an aminothiazolyl cephem, was compared to that of other cephalosporins--imipenem, aztreonam, carbenicillin, and gentamicin. CGP 31523A inhibited E. coli, K. pneumoniae, P. mirabilis, C. diversus, K. oxytoca, P. stuartii, Salmonella and Shigella at less than or equal to 0.25 micrograms/ml. It was equal or 2-fold more active than cefotaxime and ceftazidime, and 4-fold more active than imipenem against these organisms. It inhibited all carbenicillin and gentamicin-resistant isolates of these species. Neisseria and Haemophilus were inhibited by less than or equal to 0.12 micrograms/ml. Some C. freundii, E. cloacae, E. aerogenes, P. vulgaris, and P. penneri had MICs greater than or equal to 16 micrograms/ml similar to cefotaxime, ceftazidime and aztreonam. Pseudomonas were resistant, MIC 128 micrograms/ml. CGP 31523A inhibited streptococci at less than or equal to 0.25 micrograms/ml with the exception of S. faecalis, and staphylococci were inhibited by 0.5 micrograms/ml but methicillin-resistant isolates were resistant. Bacteroides and some Clostridium had MICs greater than or equal to 16 micrograms/ml. CGP 31523A was less stable than cefotaxime and ceftazidime to the plasmid TEM/SHV/PSE-4 beta-lactamases. Like cefotaxime it was hydrolyzed by the P. vulgaris type Ic beta-lactamase but not by the type Ia enzymes. CGP 31523A was not an effective beta-lactamase inhibitor nor did it induce beta-lactamases. It had overall activity comparable to available extended spectrum cephalosporins.

Aztreonam↗

Antimicrobial susceptibility profile of molecular typed cystic fibrosis Stenotrophomonas maltophilia isolates and differences with noncystic fibrosis isolates.

Multiresistance in Stenotrophomonas maltophilia limits the effectiveness of antimicrobial therapy for infections due to this organism. It can be of special concern in cystic fibrosis (CF) patients due to frequent antimicrobial administration. The in vitro activity of 41 antimicrobial agents against 76 epidemiologically defined CF S. maltophilia isolates by pulsed-field-gel electrophoresis (PFGE) technique under XbaI and SpeI restriction was compared with that obtained with 51 non-CF strains recovered from respiratory sources. Minimal inhibitory concentrations (MICs) were determined with the standard National Committee for Clinical Laboratory Standards agar dilution technique, but with 24-hr incubation. Forty-seven different PFGE profiles were observed within 76 S. maltophilia CF isolates. Minocycline (resistance rate, 0%; MIC(90), 1 microg/ml), doxycycline (6.4%; 8 microg/ml), trovafloxacin (4.2%; 2 microg/ml), moxifloxacin (6.3%; 2 microg/ml), clinafloxacin (6.3%; 2 g/ml), and moxalactam (17.0%; 64 g/ml) displayed low resistance rates. On the contrary, resistance rates were higher with ceftazidime (70.0%; 256 microg/ml), cefepime (83.0%; 128 microg/ml), piperacillin (87.2%; >1,024 microg/ml), ticarcillin (87.2%; >512 microg/ml), and aztreonam (95.7%; >1,024 microg/ml). Clavulanate reverted resistance to ticarcillin and aztreonam in 40.4% and 31.7% of strains, respectively. Aminoglycosides displayed reduced activities with susceptibility rates lower than 20% and MIC(90) higher than 128 microg/ml. With the exception of trimethoprim-sulfamethoxazole (25.4 vs. 31.3%), CF isolates were more resistant than non-CF isolates. Remarkably, resistance was enhanced in S. maltophilia isolates persistently recovered in chronically colonized patients. Susceptibility analysis demonstrated higher resistance rates among CF S. maltophilia isolates when compared with respiratory isolates from non-CF patients. Moreover, persistently recovered CF S. maltophilia isolates were more resistant than sporadic non-CF isolates.

Adolescent↗

Perspectives of beta-lactamases inhibitors in therapy of infections caused by Escherichia coli or Klebsiella with plasmidic resistance to third generation cephalosporins.

New plasmidic beta-lactamases inactivating so far stable cephalosporins, aztreonam and cephamycins restrict the use of these antibiotics in therapy of infections, e.g., by Escherichia coli and Klebsiella. Thus, combinations of beta-lactamase inhibitors and beta-lactam antibiotics were investigated in vitro with regard to their therapeutic perspectives. Minimal inhibitory concentrations and the kinetics of killing in a pharmacodynamic model were determined. Extended broad spectrum beta-lactamases (EBS-beta-lactamases) representative both for the TEM- and SHV-type were included. None of the available fixed combinations of penicillins and beta-lactamase inhibitors appears useful for therapy of infections caused by producers of EBS-beta-lactamases. In contrast, combinations of piperacillin and tazobactam or sulbactam plus cephalosporins (cefoperazone, cefotaxime, ceftazidime) or aztreonam are highly active (both by their MICs and bactericidal activity) against TEM-type EBS-beta-lactamases, but less promising for the SHV-type EBS-beta-lactamases, and plasmidic cephamycinase. Of the beta-lactams available, the monobactam carumonam and the carbapenems (imipenem, meropenem) remain safe in infections caused by E. coli and Klebsiella EBSBase producers.

Anti-Bacterial Agents↗

Bactericidal activity of cefpirome (HR 810) against 513 gram-negative bacteria isolated from blood of septicemic patients.

The profile of antibacterial activity of cefpirome was compared with that of nine other antimicrobial agents against 513 gram-negative bacteria isolated from septicemic patients. All strains were evaluated for their sensitivity by disc diffusion and broth dilution tests (MIC and MBC). Cefpirome was compared to cefazolin, cefuroxime, ceftazidime, ceftriaxone, aztreonam, imipenem, ticarcillin, tobramycin and ciprofloxacin. Among the five cephalosporins tested in this study, cefpirome was the most active against all isolates. The MIC50 and MIC90 of eight isolates of Acinetobacter calcoaceticus were 2 and 4 mg/l and those of 89 Pseudomonas aeruginosa were 2 and 8 mg/l, respectively. The MIC90 values of cefpirome for all other groups of bacteria were < or = 1 mg/l. The activity of cefpirome against gram-negative bacteria is at least as good as that of aztreonam and imipenem. The only drug showing a better profile of activity than cefpirome is ciprofloxacin. The scattergram of the 513 isolates for cefpirome MICs and inhibitory zones with the 30 micrograms disc, showed that only eight isolates were not susceptible to cefpirome. These data suggest that the in vitro activity of cefpirome is comparable to if not better than that of other beta-lactams and tobramycin.

Bacteremia↗

Outbreak of nosocomial infections due to Klebsiella pneumoniae producing SHV-4 beta-lactamase.

One hundred and fifty-four clinical isolates of Klebsiella pneumoniae resistant to broad-spectrum cephalosporins, aztreonam and amikacin were responsible for an outbreak of nosocomial infections lasting eight months in a university hospital in Paris. This outbreak occurred in the intensive care unit (39 patients), haematology units (8 patients) and surgical and medical units (11 patients). Antibiotic resistant strains were isolated from the urinary tract (48%), wound and drainage fluids (21%), respiratory tract (14%), blood (12%) and stools (5%). High resistance to oxyimino-beta-lactams was mediated by a plasmid-encoded beta-lactamase with an isoelectric point of 7.8 (SHV-4). This CAZ-type enzyme conferred a higher level of resistance to ceftazidime and aztreonam (geometric mean MIC 135 mg/l) than to cefotaxime (geometric mean MIC 14 mg/l). All isolates were of the same biotype (weakly urease positive and no sucrose fermentation). Eight Klebsiella pneumoniae strains isolated in different units and at different times of the outbreak were of the same serotype, had common plasmid patterns and harboured a large self-transferable plasmid of about 180 kilobases encoding resistance to penicillins, oxyimino-beta-lactams, aminoglycosides, tetracycline and trimethoprim. These eight large plasmids had indistinguishable EcoRI restriction patterns. These results suggest that a single strain of Klebsiella pneumoniae was responsible for this outbreak.

Anti-Bacterial Agents↗

In vitro activity of new antibiotics against Haemophilus influenzae.

The activity of sulbactam/ampicillin, aztreonam, cefetamet, cefixime, ciprofloxacin, enoxacin, fleroxacin and ofloxacin was determined against 160 Haemophilus influenzae strains using a standardized microdilution method. The strains were categorized into four groups according to beta-lactamase production and their resistance to ampicillin, chloramphenicol, erythromycin, tetracycline and cotrimoxazole. All isolates tested, regardless of their beta-lactamase production or resistance to the above mentioned drugs, were susceptible to the nine antibiotics. The most active antimicrobial agents were aztreonam, cefixime, and the two quinolone derivatives ciprofloxacin and ofloxacin.

Anti-Bacterial Agents↗

In vitro susceptibility of Aeromonas caviae, Aeromonas hydrophila and Aeromonas sobria to fifteen antibacterial agents.

In vitro testing of the activity of 15 antibacterial agents against 522 clinical isolates of Aeromonas species demonstrated some species-associated trends. Amoxicillin plus clavulanic acid was effective against approximately 45% of Aeromonas caviae and Aeromonas hydrophila, but all Aeromonas sobria isolates were resistant. Aztreonam, piperacillin and mezlocillin were highly active against all the strains of Aeromonas tested. Ticarcillin was equally effective against Aeromonas caviae and Aeromonas hydrophila, but more than 50% of Aeromonas sobria isolates were resistant. The latter species was more susceptible to cephalosporins than Aeromonas hydrophila and Aeromonas caviae. Chloramphenicol, tetracycline and trimethoprim-sulfamethoxazole were extremely active against all three Aeromonas species, likewise ofloxacin and ciprofloxacin. Aztreonam, third-generation cephalosporins, chloramphenicol and the quinolones can thus be considered for therapy of infections when Aeromonas is implicated.

Aeromonas↗

Antimicrobial susceptibility of respiratory isolates of Enterobacteriaceae and Staphylococcus aureus in Italy: incidence and trends over the period 1997-1999.

The antibiotic susceptibility of members of the family Enterobacteriaceae and of Staphylococcus aureus strains isolated from the respiratory tract was assessed over the period 1997-1999 as part of the Italian Epidemiological Observatory survey sponsored by the Smith-Kline Foundation. A standardised method was used to determine the MICs of 22 antibiotics against isolates of Klebsiella pneumoniae (n=870), Escherichia coli (n=684), Enterobacter cloacae (n=342), Enterobacter aerogenes (n=187) and Serratia marcescens (n=135) as well as the MICs of 11 antibiotics against isolates of Staphylococcus aureus (n=1,606). Overall, the susceptibility rate of Enterobacteriaceae isolates was > or = 90% to 5 agents (meropenem, imipenem, amikacin, cefepime and gentamicin); 89-80% to 2 agents (ciprofloxacin and tobramycin); and <80% to 11 agents (cefotaxime, piperacillin-tazobactam, trimethoprim-sulfamethoxazole, cefetamet, ceftriaxone, ceftazidime, aztreonam, ticarcillin-clavulanate, tetracycline, piperacillin, cefuroxime, chloramphenicol, ticarcillin, amoxicillin-clavulanate and amoxicillin). During the 3-year monitoring period, antibiotic susceptibility increased in Klebsiella pneumoniae against amoxicillin-clavulanate, in Escherichia coli against third-generation cephalosporins and aztreonam, in Enterobacter aerogenes against amoxicillin and piperacillin-tazobactam and in Serratia marcescens against most of the antibiotics. In contrast, Enterobacter cloacae showed a tendency to develop resistance to cefetamet, amikacin and ciprofloxacin. Of the total number of Staphylococcus aureus strains, 38% were methicillin resistant. Nearly 80% of the methicillin-resistant strains displayed a multiresistance pattern (additional resistance to 2 or more non-beta-lactam antibiotics). Rates of susceptibility of particular species (Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus) were compared using strains from different geographical areas of Italy (northern, central and southern) and from different nosocomial areas (outpatients, intensive care unit [ICU] inpatients, non-ICU inpatients). Susceptibility of Klebsiella pneumoniae to several antibiotics was lower in southern Italy, whereas the incidence of methicillin-resistant strains was higher in northern and central Italy. The susceptibility of Escherichia coli was similar in all three areas. No significant differences in susceptibility of Klebsiella pneumoniae or Escherichia coli were found between strains from inpatients and outpatients or from inpatients admitted to ICU and non-ICU units. The incidence of methicillin-resistant Staphylococcus aureus was higher in ICU inpatients (52%) than in non-ICU inpatients (38%) and lower in outpatients (19%) than in inpatients.

Drug Resistance, Bacterial↗

Multidrug resistant Acinetobacter baumannii isolates from a teaching hospital.

Abstract Acinetobacter baumannii is the most common nosocomial pathogen among all Acinetobacter spp. A. baumannii tend to be resistant to multiple antibiotics, and represent a severe threat in the treatment of hospitalized patients. The purpose of this study was to evaluate the prevalence, biotyping, and antibiotic resistance status of A. baumannii isolates recovered from submitted hospital clinical specimens. The in-vitro activity of 29 currently used antimicrobial agents was studied in 180 isolates of A. baumannii. The prevalence was higher in wound exudates (32%) and urine samples (22%) than in other specimens. Forty-six percent of the isolates were of biotype 9. The evolution of resistance from November 1996 through October 1998 was studied. More than 75% of the isolates were multidrug resistant (MDR) and more than 70% were #-lactamase producers. Amikacin, ampicillin + sulbactam, and imipenem are still effective antimicrobial agents, but a steady rise in the values of the minimum inhibitory concentration at which 50% of the isolates were inhibited (MIC50 )and MIC90 was observed. Resistance to aztreonam (60%), enrofloxacin (60%), imipenem (29%), moxalactam (73%), and sparfloxacin (25%) was noted; enrofloxacin and sparfloxacin are not generally used in this hospital. From the findings of the present study, no single drug appears to be suitable for empirical therapy for this nosocomial pathogen. Abstract Acinetobacter baumannii is the most common nosocomial pathogen among all Acinetobacter spp. A. baumannii tend to be resistant to multiple antibiotics, and represent a severe threat in the treatment of hospitalized patients. The purpose of this study was to evaluate the prevalence, biotyping, and antibiotic resistance status of A. baumannii isolates recovered from submitted hospital clinical specimens. The in-vitro activity of 29 currently used antimicrobial agents was studied in 180 isolates of A. baumannii. The prevalence was higher in wound exudates (32%) and urine samples (22%) than in other specimens. Forty-six percent of the isolates were of biotype 9. The evolution of resistance from November 1996 through October 1998 was studied. More than 75% of the isolates were multidrug resistant (MDR) and more than 70% were #-lactamase producers. Amikacin, ampicillin + sulbactam, and imipenem are still effective antimicrobial agents, but a steady rise in the values of the minimum inhibitory concentration at which 50% of the isolates were inhibited (MIC50) and MIC90 was observed. Resistance to aztreonam (60%), enrofloxacin (60%), imipenem (29%), moxalactam (73%), and sparfloxacin (25%) was noted; enrofloxacin and sparfloxacin are not generally used in this hospital. From the findings of the present study, no single drug appears to be suitable for empirical therapy for this nosocomial pathogen.

Acinetobacter baumannii↗

Aminoglycosides plus beta-lactams against gram-negative organisms. Evaluation of in vitro synergy and chemical interactions.

Combination antibiotic therapy has been used mainly to broaden the antibacterial spectrum and prevent the development of resistance. Antibiotic combinations proven to be synergistic in vitro are associated with a significantly better in vivo response, particularly in the compromised host in whom traditional treatment combines an antipseudomonal penicillin plus an aminoglycoside. Several investigators have examined combining new agents, such as the third-generation cephalosporins (cefotaxime, ceftriaxone, ceftizoxime, ceftazidime, cefoperazone, and moxalactam), aztreonam, or the ureidopenicillins, with amikacin. When compared with combinations of an older cephalosporin, carbenicillin or ticarcillin, plus gentamicin or tobramycin, these newer combinations produce higher rates of clinically meaningful synergy and rapid enhancement of in vitro bactericidal activity against the difficult-to-treat Enterobacteriaceae (i.e., Serratia, Citrobacter, Enterobacter, Providencia, and indole-positive Proteus species). This effect, without any evidence of antagonism, has been reported even for strains moderately or completely resistant to the former antibiotics. Unsatisfactory and unpredictable synergistic interactions against both resistant and susceptible strains of Pseudomonas aeruginosa--the most difficult nosocomial pathogen to treat--have been noted with combinations of tobramycin or gentamicin plus cefotaxime, moxalactam, or cefoperazone. Conversely, the use of amikacin plus various beta-lactams against multi-resistant strains is more frequently synergistic. Agents have been observed to exhibit such synergy in the following order of activity, from most to least synergistic: ceftazidime, ceftriaxone, moxalactam, aztreonam, cefotaxime, azlocillin, cefoperazone, cefsulodin, and carbenicillin. The combination of amikacin plus imipenem or ciprofloxacin against strains of P. aeruginosa resistant to the former and moderately resistant to the latter was recently reported to have a low probability of synergy; the combination of two of the newer beta-lactams had mostly an unpredictable or even antagonistic result. In vitro studies have also demonstrated that high concentrations of the antipseudomonal penicillins can inactivate the aminoglycosides. Among the latter compounds, the inactivation order, from most to least inactivated, was as follows: tobramycin, gentamicin, netilmicin, and amikacin. To date, the reports of aminoglycoside inactivation by the newer cephalosporins have been rather contradictory; only moxalactam has been shown produce a significant decrease in activity.

Amikacin↗

Quantitative relationship between sensitivity to beta-lactam antibiotics and beta-lactamase production in gram-negative bacteria--II. Non-steady-state treatment and progress curves.

A non-steady-state model is discussed for the study of the interplay between beta-lactamase activity and outer membrane permeability with slowly hydrolysed beta-lactams. The analysis shows: (1) that the simple, steady-state model presented in the accompanying paper remains valid as long as kcat (i.e. k3 with chromosome-encoded class C beta-lactamases) is larger than 10(-3)/sec (generation time = 20 min or more); (2) that among the beta-lactam antibiotics studied here, the complete, non-steady-state model needs only be used in the case of aztreonam; (3) that the term "trapping" should be replaced by "formation of a covalent acyl-enzyme" and that such a phenomenon only contributes significantly to the resistance when penetration and hydrolysis are very slow and the periplasmic beta-lactamase concentration is very high. Aztreonam seems to be the only compound which fulfils the first two conditions.

Anti-Bacterial Agents↗

Synergistic interactions of ciprofloxacin and extended spectrum beta-lactams or aminoglycosides against Acinetobacter calcoaceticus ss. anitratus.

The susceptibility of 54 clinical isolates of Acinetobacter calcoaceticus ss. anitratus to 16 antimicrobial agents was determined in vitro with inoculum of 10(4) and 10(6) cfu by a standard agar dilution method. The most active agents were imipenem, SCH 34343, ciprofloxacin, difloxacin (A-56619), and A-56620. Only imipenem and Abbott quinolones (A-56619 and A-56620) remained active when tested with the heavier inoculum. Except for ticarcillin and ceftazidime, which showed only moderate activity, the extended-spectrum penicillins and cephalosporins, as well as aztreonam and aminoglycosides, were inactive against these highly resistant strains. Nine isolates were selected for combination studies of ciprofloxacin with seven beta-lactams and three aminoglycosides using a checkerboard agar dilution technique. Synergistic or additive interactions at clinically achievable concentrations were more common with amikacin (eight isolates), tobramycin (seven), ceftazidime (six), cefoperazone (six), and aztreonam (six), than with other agents, including mezlocillin (four), piperacillin (three), gentamicin (two), and cefsulodin (two). Antagonism was rare, only occurring with mezlocillin in a single strain. These data suggest that combinations of ciprofloxacin with these agents may be useful for some nosocomial multidrug resistant A. calcoaceticus ss. anitratus infections.

Acinetobacter↗

Resistance of Xanthomonas maltophilia to antibiotics and the effect of beta-lactamase inhibitors.

We examined the susceptibility of 50 isolates of Xanthomonas maltophilia and the effect of beta-lactamase inhibitors upon the susceptibility. The majority of isolates were resistant to azlocillin, piperacillin, mezlocillin, ticarcillin, cefotaxime, ceftizoxime, ceftriaxone, cefoperazone, and ceftazidime. All isolates were resistant to imipenem, CGP 31608, aztreonam, and carumonam. Although disk susceptibility tests showed that the combination of clavulanate with ticarcillin inhibited many isolates, at a ratio of 1:20 few isolates were susceptible to the combination. Addition of clavulanate to aztreonam and to imipenem failed to make organisms susceptible. Sulbactam combined with cefoperazone made some organisms susceptible, but ampicillin-sulbactam was ineffective, whereas tazobactam combined with piperacillin at a ratio of 1:4 made half the isolates have MICs of 32 micrograms/ml or less. The beta-lactamases from the isolates hydrolyzed all of the beta-lactams.

Anti-Bacterial Agents↗

Susceptibility testing accuracy of a CTX-M-type extended-spectrum beta-lactamase organism-producing population of Enterobacteriaceae: intermethod analysis for 9 beta-lactams.

To assess the wide geographical applicability of the current and proposed susceptibility breakpoint criteria for 9 beta-lactam antimicrobials, the performance characteristics of 2 standardized methods were analyzed by testing a contemporary collection of 354 isolates of Enterobacteriaceae, enriched (76; 21.5%) for extended-spectrum beta-lactamase (ESBL)-producing strains. Molecular characterization of 57 ESBL strains revealed that majority of the strains (94.7%) were CTX-M type, with a predominance (85.2%) of CTX-M-14 and -3 types, those types prevalent in China. Bloodstream isolates constituted 68.6% of the entire collection. The 9 beta-lactam antimicrobials analyzed were aztreonam, cefepime, cefotaxime, cefotetan, cefoxitin, ceftazidime, ceftriaxone, ceftizoxime, and cefuroxime. Reference broth microdilution minimal inhibitory concentration (MIC) results were compared to those zone diameters obtained by disk diffusion testing. The regression coefficient was acceptable for most antimicrobials, ranging from r = 0.84 (cefotetan) to r = 0.98 (cefotaxime, cefuroxime, and ceftriaxone). Using the current breakpoint criteria, the absolute intermethod categorical agreement was acceptable for 8 of the 9 antimicrobials (not cefoxitin, 85.1%) ranging from 92.6% (cefotaxime) to 97.8% (ceftazidime). Very major (false-susceptible) and major (false-resistant) errors were nil (0.0%) for 5 of the beta-lactams and minor errors ranged from 0.8% (cefotetan) to 14.1% (cefoxitin). The proposed (generally lower) MIC breakpoint criteria also had acceptable intermethod concordance ranging from 91.6% (cefoxitin) to 99.2% (cefotaxime and ceftriaxone). Furthermore, an improvement in the intermethod absolute categorical agreement ranging from +0.8% (ceftazidime) to +6.6% (cefotaxime) was observed for 7 of 9 antimicrobials tested, including the ESBL screening test compounds (aztreonam, ceftazidime, cefotaxime, and ceftriaxone). No modification of the susceptible breakpoint criteria, with removal of the intermediate category, was proposed for cefoxitin and cefuroxime, resulted in a shift of error type from minor to major or very major, but the categorical agreement improved (+ >or=1.2%) for both cephems. In conclusion, our results confirm that both the current and the proposed MIC breakpoint criteria with appropriately selected zone diameter correlates have acceptable intermethod error rates even when tested against an Enterobacteriaceae collection enriched with CTX-M-type ESBL-producing strains that are endemic in locations (China) outside the United States.

Anti-Bacterial Agents↗

Plasmid-mediated, inducible AmpC beta-lactamase (DHA-1)-producing Enterobacteriaceae at a Korean hospital: wide dissemination in Klebsiella pneumoniae and Klebsiella oxytoca and emergence in Proteus mirabilis.

The aim of the study was to investigate the phenotypic and genetic characteristics of recently emerging cefoxitin-resistant and induction-positive isolates of Escherichia coli, Klebsiella species, and Proteus mirabilis. Strains of Enterobacteriaceae were isolated at a Korean tertiary care hospital between June and December 2002. Induction was tested using cefoxitin and aztreonam disks, the blaDHA allele was detected by PCR, and pulsed-field gel electrophoresis (PFGE) patterns were also analyzed. Among the cefoxitin-resistant isolates, 2.7% of E. coli, 21.1% of Klebsiella pneumoniae, 32.0% of Klebsiella oxytoca, and 8.3% of P. mirabilis isolates showed induction, and were blaDHA-1 allele positive. To the best of our knowledge, this is the first report of blaDHA-1 in P. mirabilis. The MICs of ceftazidime, cefotaxime, and aztreonam increased significantly by higher inoculum, suggesting that their clinical usefulness is limited. Presence of multiple PFGE patterns and identical patterns in some isolates suggest that the widely disseminated blaDHA-1 in Klebsiella species was because of both horizontal and clonal spread.

Anti-Bacterial Agents↗