Showing papers on "Aztreonam published in 2001"
TL;DR: K. pneumoniae strain 1534 is mainly due to production of a novel Bush group 2f, class A, carbapenem-hydrolyzing β-lactamase, KPC-1, although alterations in porin expression may also play a role.
Abstract: A Klebsiella pneumoniae isolate showing moderate to high-level imipenem and meropenem resistance was investigated. The MICs of both drugs were 16 microg/ml. The beta-lactamase activity against imipenem and meropenem was inhibited in the presence of clavulanic acid. The strain was also resistant to extended-spectrum cephalosporins and aztreonam. Isoelectric focusing studies demonstrated three beta-lactamases, with pIs of 7.2 (SHV-29), 6.7 (KPC-1), and 5.4 (TEM-1). The presence of bla(SHV) and bla(TEM) genes was confirmed by specific PCRs and DNA sequence analysis. Transformation and conjugation studies with Escherichia coli showed that the beta-lactamase with a pI of 6.7, KPC-1 (K. pneumoniae carbapenemase-1), was encoded on an approximately 50-kb nonconjugative plasmid. The gene, bla(KPC-1), was cloned in E. coli and shown to confer resistance to imipenem, meropenem, extended-spectrum cephalosporins, and aztreonam. The amino acid sequence of the novel carbapenem-hydrolyzing beta-lactamase, KPC-1, showed 45% identity to the pI 9.7 carbapenem-hydrolyzing beta-lactamase, Sme-1, from Serratia marcescens S6. Hydrolysis studies showed that purified KPC-1 hydrolyzed not only carbapenems but also penicillins, cephalosporins, and monobactams. KPC-1 had the highest affinity for meropenem. The kinetic studies also revealed that clavulanic acid and tazobactam inhibited KPC-1. An examination of the outer membrane proteins of the parent K. pneumoniae strain demonstrated that the strain does not express detectable levels of OmpK35 and OmpK37, although OmpK36 is present. We concluded that carbapenem resistance in K. pneumoniae strain 1534 is mainly due to production of a novel Bush group 2f, class A, carbapenem-hydrolyzing beta-lactamase, KPC-1, although alterations in porin expression may also play a role.
1,439 citations
TL;DR: It is clinically important to detect ESBL production by klebsiellae or E. coli even when cephalosporin MICs are in the susceptible range (≤ 8 μg/ml) and to report ESBL-producing organisms as resistant to aztreonam and all cep Halosporins (with the exception of cephamycins).
Abstract: Although extended-spectrum beta-lactamases (ESBLs) hydrolyze cephalosporin antibiotics, some ESBL-producing organisms are not resistant to all cephalosporins when tested in vitro. Some authors have suggested that screening klebsiellae or Escherichia coli for ESBL production is not clinically necessary, and when most recently surveyed the majority of American clinical microbiology laboratories did not make efforts to detect ESBLs. We performed a prospective, multinational study of Klebsiella pneumoniae bacteremia and identified 10 patients who were treated for ESBL-producing K. pneumoniae bacteremia with cephalosporins and whose infecting organisms were not resistant in vitro to the utilized cephalosporin. In addition, we reviewed 26 similar cases of severe infections which had previously been reported. Of these 36 patients, 4 had to be excluded from analysis. Of the remaining 32 patients, 100% (4 of 4) patients experienced clinical failure when MICs of the cephalosporin used for treatment were in the intermediate range and 54% (15 of 28) experienced failure when MICs of the cephalosporin used for treatment were in the susceptible range. Thus, it is clinically important to detect ESBL production by klebsiellae or E. coli even when cephalosporin MICs are in the susceptible range (≤ 8 μg/ml) and to report ESBL-producing organisms as resistant to aztreonam and all cephalosporins (with the exception of cephamycins).
565 citations
TL;DR: To evaluate the prevalence of extended-spectrum beta-lactamase (ESBL)-producing strains among species of Enterobacteriaceae, a microdilution susceptibility test was performed with strains of Klebsiella pneumoniae, Escherichia coli, Proteus mirabilis, and Salmonella species that were isolated as part of the SENTRY project.
Abstract: To evaluate the prevalence of extended-spectrum beta-lactamase (ESBL)-producing strains among species of Enterobacteriaceae, a microdilution susceptibility test was performed with strains of Klebsiella pneumoniae, Escherichia coli, Proteus mirabilis, and Salmonella species that were isolated as part of the SENTRY project. The highest percentage of ESBL phenotype (defined as a minimum inhibitory concentration [MIC] > or =2 microg/mL for ceftazidime, ceftriaxone, or aztreonam) was detected among K. pneumoniae strains from Latin America (45%), followed by those from the Western Pacific region (25%), Europe (23%), the United States (8%), and Canada (5%). P. mirabilis and E. coli strains for which MICs of extended-spectrum cephalosporins or monobactams were elevated also were more prominent in Latin America. Testing with ceftazidime revealed more isolates with elevated MICs than did testing with ceftriaxone or aztreonam. ESBL strains showed high levels of co-resistance to aminoglycosides, tetracycline, trimethoprim-sulfamethoxazole, and ciprofloxacin. Imipenem remains highly effective against ESBL strains. Organisms expressing an ESBL are widely distributed worldwide, although prevalence rates are significantly higher in certain geographic regions.
495 citations
TL;DR: The refined three-dimensional structure of the class C beta-lactamase from Citrobacter freundii is reported, confirming the predicted structural similarity and leading to the hypothesis that Tyr 150 functions as a general base during catalysis.
Abstract: BETA-LACTAMASES (EC 3.5.2.6, 'penicillinases') are a family of enzymes that protect bacteria against the lethal effects of cell-wall synthesis of penicillins, cephalosporins and related antibiotic agents, by hydrolysing the β-lactam antibiotics to biologically inactive compounds. Their production can, therefore, greatly contribute to the clinical problem of antibiotic resistance1–4. Three classes of β-lactamases—A, B and C—have been identified on the basis of their amino-acid sequence; class B β-lactamases are metalloenzymes, and are clearly distinct from members of class A and Cβ-lactamases5, which both contain an active-site serine residue involved in the formation of an acyl enzyme with β-lactam substrates during catalysis6–12. It has been predicted that class C β-lactamases share common structural features with D,D-carboxypeptidases and class A β-lactamases, and further, suggested that class A and class Cβ-lactamases have the same evolutionary origin as other β-lactam target enzymes13,14. We report here the refined three-dimensional structure of the class C β-lactamase from Citrobacter freundii12,15 at 2.0-A resolution and confirm the predicted structural similarity. The refined structure of the acyl-enzyme formed with the monobactam inhibitor aztreonam at 2.5-A resolution defines the enzyme's active site and, along with molecular modelling, indicates a mechanism for β-lactam hydrolysis. This leads to the hypothesis that Tyr 150 functions as a general base during catalysis.
275 citations
TL;DR: P. aeruginosa ED-1, isolated from a pulmonary brush of a patient hospitalized in a suburb of Paris, France, was resistant to ceftazidime and of intermediate susceptibility to ureidopenicillins and to cefotaxime.
Abstract: Pseudomonas aeruginosa ED-1, isolated from a pulmonary brush of a patient hospitalized in a suburb of Paris, France, was resistant to ceftazidime and of intermediate susceptibility to ureidopenicillins and to cefotaxime. Cloning and expression of the beta-lactamase gene content of this isolate in Escherichia coli DH10B identified a novel OXA-10 variant, OXA-28, with a pI value of 8.1 and a molecular mass of 29 kDa. It differed from OXA-10 by 10 amino acid changes and from OXA-13 and OXA-19 by 2 amino acid changes, including a glycine instead of tryptophan at position 164, which is likely involved in its resistance to ceftazidime. Like OXA-11, -14, -16, and -19 and as opposed to OXA-17, OXA-28 predominantly compromised ceftazidime and had only marginal effect on the MICs of aztreonam and cefotaxime in P. aeruginosa. Once expressed in E. coli, OXA-28 raised the MIC of ceftazidime to a much higher level than those of amoxicillin, cephalothin, and cefotaxime (128, 16, 8, and 4 microg/ml, respectively). OXA-28 beta-lactamase had a broad spectrum of activity, including ceftazidime. Its activity was partially antagonized by clavulanic acid (50% inhibitory concentration, 10 microM) and NaCl addition. The oxa28 gene cassette was inserted in the variable region of a class 1 integron, In57, immediately downstream of an amino 6'-N-acetyltransferase gene cassette, aac(6')Ib. The structures of the integrons carrying either oxa28, oxa13, or oxa19 gene cassettes were almost identical, suggesting that they may have derived from a common ancestor as a result of the common European origin of the P. aeruginosa isolates. In57 was located on a self-transferable plasmid of ca. 150 kb that was transferred from P. aeruginosa to P. aeruginosa.
130 citations
TL;DR: The antibiotic susceptibilities of non-fermenting Gram-negative bacterial strains isolated from immunocompromised patients are examined for the first time, and it is shown that some strains are able to persist at the "in-use" concentration of particular biocides.
87 citations
TL;DR: Despite prolonged and intensive antibiotic treatment, susceptible mucoid isolates were isolated from the CF sputum, possibly because these bacteria are protected from the selective pressure of antibiotics by the resistant non-mucoid isolate co-existing in the biofilm in the lungs of CF patients.
Abstract: The purpose of this study was to characterize 42 paired mucoid and non-mucoid Danish cystic fibrosis (CF) Pseudomonas aeruginosa isolates collected in 1997, by RiboPrinting, antibiotic susceptibility and beta-lactamase activity. Eight P. aeruginosa isolates collected before 1991 were included for comparison. Eighteen of the 42 paired mucoid and non-mucoid isolates showed the same ribotype; the remaining 24 belonged to different ribogroups. Mucoid isolates showed higher susceptibility to antibiotics and lower beta-lactamase activity compared with non-mucoid isolates. Significant differences (P < or = 0.01) between mucoid and non-mucoid isolates were found for the meropenem and colistin MICs for the isolates with the same ribotype, and for the MICs of ceftazidime, piperacillin, aztreonam, meropenem, tobramycin, ciprofloxacin and in the basal levels of beta-lactamase for the paired isolates belonging to different ribogroups. A dominant ribotype 73-S2 with hyperinducible beta-lactamase production and significantly higher MICs of piperacillin, meropenem and tobramycin compared with the other major ribotypes (73-S1, 207-S3 and 227-S8) was present among the 84 CF isolates. The isolates collected before 1991 had an antibiotic susceptibility pattern similar to the 1997 isolates. Despite prolonged and intensive antibiotic treatment, susceptible mucoid isolates were isolated from the CF sputum, possibly because these bacteria are protected from the selective pressure of antibiotics by the resistant non-mucoid isolates co-existing in the biofilm in the lungs of CF patients.
86 citations
TL;DR: Restriction fragment length polymorphism DNA typing revealed that the outbreak of cefozopran-resistant isolates in Kitakyushu, Japan, occurred as a result of clonal spread.
Abstract: We have previously reported that the Neisseria gonorrhoeae isolates from clinical failure cases treated with cefdinir and aztreonam, beta-lactams exhibited high MICs. These resistant isolates were clearly separated from the isolates exhibiting a low level of resistance to beta-lactams as shown by the MIC distribution of cefozopran. Restriction fragment length polymorphism DNA typing revealed that the outbreak of cefozopran-resistant isolates in Kitakyushu, Japan, occurred as a result of clonal spread.
84 citations
TL;DR: A phenyl mannitol broth containing ceftizoxime and aztreonam (PHMB+) improved the rate of MRSA detection, and in a clinical setting, 40 MRSA strains were detected with PHMB+, compared with only 23 detected with a routine method.
Abstract: We tested a phenyl mannitol broth containing ceftizoxime and aztreonam
(PHMB(+)) for detection of methicillin-resistant Staphylococcus aureus
(MRSA) with reference MRSA strains and, subsequently, with clinical
samples (n = 1,098). All reference MRSA strains induced color change in
PHMB(+) after 24 to 72 h of incubation. In a clinical setting, 40 MRSA
strains were detected with PHMB(+), compared with only 23 detected with a
routine method. Thus, this selective broth significantly (P < 0.001)
improved the rate of MRSA detection.
82 citations
TL;DR: In Japan, patients with gonococcal urethritis caused by these resistant N. gonorrhoeae strains should be treated with cefodizime or spectinomycin, because of the serious problem that these isolates were already resistant to non-β-lactam antimicrobials.
74 citations
TL;DR: A critical evaluation of the English literature was performed on treatment outcomes associated with ESBL‐producing Enterobacteriaceae and Discordant outcomes in relation to in vitro susceptibility of the agent did not occur exclusively with cephalosporins but with all drugs including imipenem.
Abstract: The emergence of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, particularly Escherichia coli and Klebsiella pneumoniae, presents significant diagnostic and therapeutic challenges to the management of infections due to these organisms. Detection of resistant isolates is difficult based on routine susceptibility testing performed by a clinical microbiology laboratory. In addition, the utility of penicillins, cephalosporins, and aztreonam in treating serious infections due to these organisms is uncertain due to reports of treatment failure despite apparent in vitro susceptibility. A critical evaluation of the English literature was performed on treatment outcomes associated with ESBL-producing Enterobacteriaceae. Imipenem and extended-spectrum cephalosporins were commonly administered. Discordant outcomes in relation to in vitro susceptibility of the agent did not occur exclusively with cephalosporins but with all drugs including imipenem. Until more outcome data are available, drug selection must take into consideration whether or not an outbreak is occurring and whether therapy is empirical or definitive.
TL;DR: In this paper, the authors evaluated the relationship between serum pharmacokinetics, pharmacodynamics, pathogen susceptibility, and clinical outcomes in patients receiving aztreonam or tobramycin monotherapy.
TL;DR: Results indicate that the newer fluoroquinolones or the triple combination of ticarcillin/clavulanate plus aztreonam may be potential options for treatment of infection caused by S. maltophilia in patients who are intolerant to or fail trimethoprim/sulfamethoxazole therapy.
TL;DR: The objective of this study was to determine the susceptibility of Arcobacter butzleri isolates to various antimicrobial agents used in the treatment of infectious diseases in humans and animals.
Abstract: Aims: The objective of this study was to determine the susceptibility of Arcobacter butzleri isolates to various antimicrobial agents used in the treatment of infectious diseases in humans and animals. Methods and Results: Thirty-nine A. butzleri strains isolated from broiler chickens were tested for their susceptibility to 23 antimicrobial agents using a disc diffusion method. All isolates were resistant to aztreonam, cefuroxime sodium, cephalothin, orbenin, oxacillin, penicillin G and trimethoprim/sulphamethoxazol. Of the 39 isolates tested, 26 were also found resistant to amoxycillin, amoxycillin/clavulanic acid and ampicillin. One isolate was resistant to, and four showed intermediate level of resistance to, erythromycin. All isolates were susceptible to amikacin, chloramphenicol, danofloxacin, enrofloxacin, nitrofurantoin, nalidixic acid, tetracyclines and tobramycin. Conclusions: The majority of the isolates were found resistant to antibiotics commonly used for the treatment of infectious bacterial diseases in humans and animals. Significance and Impact of the Study: This study shows that A. butzleri strains vary in their resistance to certain kinds of antibiotics and caution should be taken when choosing a suitable antibiotic for the treatment of disease(s) caused by this organism.
TL;DR: Enterobacter hormaechei was the species most susceptible to fosfomycin, and beta-Lactam susceptibility patterns pointed to the presence of chromosomally-encoded AmpC enzymes in all taxa of the E. cloacae complex.
TL;DR: Piperacillin-tazobactam, as well as amikacin and meropenem appear to be important therapeutic options for infections due to multidrug-resistant, ESBL-producing P. mirabilis.
TL;DR: Taking into account the species distribution and the prevalence of resistance, cefepime, imipenem, amikacin and gentamicin appeared generally suitable for empirical therapeutic use in severe ICU-acquired Gram-negative infections in Belgium, but the therapeutic strategy should be adapted according to the local ecology of resistance.
Abstract: Objective : to assess the distribution and prevalence of resistance rates among Gram-negative isolates in Belgian intensive care units (ICUs) between 1996 and 1999. Methods : During 1996-1997 and 1998-1999, over a total period of 10 and 9 months respectively, members of the NPRS Belgian Study group collected, on clinical indications, 3029 consecutive initial isolates of Gramnegative bacteria from patients admitted to 26 Belgian hospitals and performed minimal inhibitory concentration (MIC) determinations by means of the E-test. Breakpoints were defined according to the criteria of the NCCLS. Results : The overall distribution of bacterial species was, in decreasing order of frequency : Pseudomonas aeruginosa >E. coli >E. aerogenes >K., pneumoniae >P. mirabilis >S. marcescens >E. cloacae >K. oxytoca >M. morganii >Stenotrophomonas maltophilia >Acinetobacter spp. All together these species and genera constituted about 90% of all isolates. The frequency of resistance for all the initial Gram-negative isolates in 1998-9 were : amoxicillin-clavulanic acid 60%, piperacillin 31%, piperacillin-tazobactam 20%, cefuroxime 58%, ceftriaxone 31%, ceftazidime 17%, aztreonam 23%, cefepime 10%, imipenem 13%, gentamicin 12%, amikacin 12% and ciprofloxacin 21%. Apart for an increase in multiple drug resistance among P. aeruginosa isolates, no significant trends were observed neither in species distribution nor in the overall prevalence of antimicrobial resistance among Gramnegative isolates from Belgian ICUs between 1996-7 and 1998-9. Conclusions : Among Gram-negative isolates in Belgian ICUs, a very high frequency of resistance was seen to amoxicillin-clavulanic acid and cefuroxime, and rather high frequencies of resistance to piperacillin, ceftriaxone and,aztreonam. Taking into account the species distribution and the prevalence of resistance, cefepime, imipenem, amikacin and gentamicin appeared generally suitable for empirical therapeutic use in severe ICU-acquired Gram-negative infections in Belgium. However, the therapeutic strategy should be adapted according to the local ecology of resistance.
TL;DR: The natural susceptibility of 74 Plesiomonas shigelloides strains isolated from humans, water, and animals (n = 2) to 71 antibiotics was examined using a microdilution procedure with Mueller-Hinton broth and an inoculum of 1 x 10(6) cfu/mL.
Abstract: The natural susceptibility of 74 Plesiomonas shigelloides strains isolated from humans (n = 50), water (n = 22) and animals (n = 2) to 71 antibiotics was examined. MICs were performed using a microdilution procedure with Mueller-Hinton broth and an inoculum of 1 x 10(6) cfu/mL. Plesiomonas strains were naturally susceptible or naturally susceptible and intermediate to tetracyclines, several aminoglycosides, aminopenicillins in combination with beta-lactamase inhibitors, all cephalosporins except cefoperazone, ceftazidime and cefepime, carbapenems, aztreonam, quinolones, trimethoprim, sulfamethoxazole, azithromycin, chloramphenicol, nitrofurantoin and fosfomycin. Uniform natural resistance was found to all penicillins tested, roxithromycin, clarithromycin, lincosamides, streptogramins, glycopeptides and fusidic acid. Plesiomonas strains were naturally resistant and intermediate to streptomycin, erythromycin and rifampicin. There were two susceptibility patterns to piperacillin/tazobactam, several cephalosporins and aztreonam. In contrast to a previous study with beta-lactam antibiotics, susceptibility testing of non-beta-lactams revealed no alterations of the MICs of most antibiotics, using different inocula and media. A database is described of the natural susceptibility of P. shigelloides strains to a wide range of antibiotics. It can be used for the validation of susceptibility test results of these bacteria.
TL;DR: Klebsiella oxytoca strains resistant to both aztreonam and ceftriaxone strains isolated from six neonates in a neonatal intensive care unit and water reservoirs of two humidifiers attached to the neonatal incubators established that the drug resistance was attributed to overproduction of chromosomally encoded Kl β-lactamase.
Patent•
20 Dec 2001
TL;DR: A method and a composition for treatment of pulmonary bacterial infections caused by gram-negative bacteria was proposed in this paper, using a concentrated formulation of aztreonam or a pharmaceutically acceptable salt thereof, delivered as an aerosol or dry powder formulation.
Abstract: A method and a composition for treatment of pulmonary bacterial infections caused by gram-negative bacteria suitable for treatment of infection caused by Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Pseudomonas aeruginosa, Haemophilus influenzae, Proteus mirabilis, Enterobacter species, Serratia marcescens as well as those caused by Burkholderia cepacia, Stenotrophomonas maltophilia, Alcaligenes xylosoxidans, and multidrug resistant Pseudomonas aeruginosa, using a concentrated formulation of aztreonam, or a pharmaceutically acceptable salt thereof, delivered as an aerosol or dry powder formulation.
TL;DR: It is found that most SHV-producing klebsiellae have MICs of cefpirome that imply susceptibility at the moderate inoculum size, in spite of the fact that, according to the NCCLS, all ESBL producers should be considered resistant to all cephalosporins, independent of MIC values.
TL;DR: Imipenem and meropenem resistance due to production of carbapenem-hydrolyzing enzymes among clinical isolates is still very rare, but microbiology laboratories should be aware of these chromosomally encoded enzymes among class C beta-lactamases producing enteric bacilli such as S. marcescens and Enterobacter cloacae.
TL;DR: Pseudomonas aeruginosa clinical isolate PA35 is resistant to amino- and ureido-penicillins, has intermediate susceptibility to cefsulodin, cefepime and aztreonam, and is susceptible to imipenem and ceftazidime, and a new beta-lactamase variant, OXA-35, is revealed.
Abstract: Pseudomonas aeruginosa clinical isolate PA35 is resistant to amino- and ureido-penicillins, has intermediate susceptibility to cefsulodin, cefepime and aztreonam, and is susceptible to imipenem and ceftazidime. Cloning and sequencing revealed a new beta-lactamase variant, OXA-35, sharing 96% amino acid identity with OXA-10. OXA-35 displays a restricted-substrate hydrolysis profile with improved hydrolysis of amoxicillin and cloxacillin compared with OXA-10. OXA-35 differs from derivatives OXA-19 and OXA-28 by one amino acid substitution and may be a progenitor of these OXA-13-like extended-spectrum beta-lactamases.
TL;DR: A database on the natural susceptibility of Brevibacterium casei, Dermabacter hominis, and Turicella otitidis to a wide range of antibiotics is described, which can be applied for the validation of susceptibility testing results of these recently established coryneform bacteria.
Abstract: The natural susceptibility of 20 strains each of Brevibacterium casei (formerly CDC coryneform groups B-1 and B-3), Dermabacter hominis (formerly CDC coryneform groups 3 and 5), and Turicella otitidis (formerly coryneform group ANF-1-like) isolated from clinical specimens to 71 antibiotics was investigated. Susceptibility testing was carried out with a microdilution procedure using H medium. All three species were naturally sensitive to tetracyclines, most aminoglycosides, carbapenems, macrolides, lincosamides, glycopeptides, and rifampin. Susceptibility patterns indicating natural resistance to pipemidic acid, sulfamethoxazole, and cotrimoxazole also were found for all three species. Species-dependent discrepancies in susceptibility leading to completely different categorizations (changing from sensitive to resistant or vice versa) were found for some penicillins (e.g., oxacillin and amoxicillin), a few cephalosporins (e.g., ceftibutene), aztreonam, tobramycin, norfloxacin, fleroxacin, trimethoprim, nitrofurantoin, fosfomycin, and fusidic acid. For the majority of antibiotics, Brevibacterium casei was the least susceptible species and Turicella otitidis the most susceptible taxon. The present study describes a database on the natural susceptibility of Brevibacterium casei, Dermabacter hominis, and Turicella otitidis to a wide range of antibiotics. This database can be applied for the validation of susceptibility testing results of these recently established coryneform bacteria.
Journal Article•
TL;DR: The incidence of ES beta L producing strains of Klebsiella and other members of enterobacteriaceae should be carefully monitored in children to prevent unnecessary use of antibiotics especially 3GC and aminoglycoside antibiotics.
Abstract: BACKGROUND & OBJECTIVES Extended spectrum beta-lactamases (ES beta L) are enzymes produced in some Gram-negative bacilli that mediate resistance to third generation cephalosporins (3GC) and aztreonam. These are common in Klebsiella spp. and Escherichia coli and in other members of the family enterobacteriaceae. ES beta L production is accompanied by resistance to other antibiotics as these are encoded by multi drug resistance conjugative plasmids. The present study was undertaken to study the incidence of multi drug resistant and ES beta L producing Klebsiella spp. in children under five years of age suffering from intestinal and extraintestinal infections. METHODS A total of 90 strains of Klebsiella spp. (76 isolates of K. pneumoniae and 14 of K. oxytoca) were tested for resistance to 3GC antibiotics (ceftazidime, cefotaxime, ceftriaxone), amikacin, ampicillin, erythromycin, gentamycin and streptomycin by disc diffusion method. Isolates found resistant to 3GC antibiotics were tested for the production of ES beta L by double disc diffusion synergy test. Transconjugation experiments were done to study the transfer of drug resistance and ES beta L production from Klebsiella isolates to an Esch. coli strain (K12 J62-2). RESULTS All the 90 isolates showed multi drug resistance; 87 (96.6%) isolates showed resistance or decreased susceptibility to at least one of the three 3GC. ES beta L production was detected in four strains of K. pneumoniae and two K. oxytoca. ES beta L activity could be experimentally transferred to recipient Esch. coli in all the 6 isolates. Resistance to beta-lactam antibiotics was co-transferred along with resistance to gentamycin. INTERPRETATION & CONCLUSION This study has shown the incidence of ES beta L producing Klebsiella strains in children in Chennai, and possibly poses a threat in the treatment and management of Klebsiella associated infections. The incidence of ES beta L producing strains of Klebsiella and other members of enterobacteriaceae should be carefully monitored in children to prevent unnecessary use of antibiotics especially 3GC and aminoglycoside antibiotics. Hence, tests for the detection of ES beta L producing Klebsiella strains should be carried out routinely for better therapeutic management.
TL;DR: Cftazidime, remained the best cephalosporin except against the strains overexpressing the chromosomal type 1 beta-lactamase, and cefepime was less affected by the overproduction of constitutive cEPhalosporainase, which was probably related with non enzymatic mechanisms.
TL;DR: The in vitro susceptibility of B. burgdorferi to mezlocillin, meropenem, aztreonam, vancomycin, teicoplanin, ribostamycin and fusidic acid is explored and the excellent in vitro effectiveness of acylamino-penicillin derivatives is emphasised.
TL;DR: In conclusion, antimicrobial management of BCC in CF remains a complex problem, and hence some form of synergy testing, especially testing to examine and prevent antagonism, should form a basis to help guide more efficacious combinations of agents used.
Abstract: a population of 230 (3%), and all of these children have B. cepacia genomovar III. Antimicrobial susceptibility assays were performed on all recent BCC isolates employing a modified Stokes’ disc diffusion assay on DST agar (Oxoid Ltd, Basingstoke, UK) supplemented with 5% v/v defibrinated horse blood, with the following antibiotics (� g): ciprofloxacin (5), colistin (10), ceftazidime (30), azlocillin (75), aztreonam (30), imipenem (10), gentamicin (10), tobramycin (10), meropenem (10), amikacin (30), temicillin (30) and piperacillin/tazobactam (110). Antibiotic disc concentrations were similar for adults and children with the exception of colistin, which was 25 � g for testing with children. Susceptibility data are shown in the Table. Overall, the paediatric isolates were more susceptible to several antibiotics than the adult BCC organisms, and this may allow for an opportunity to attempt to eradicate the organism on first isolation from the lung, when the organism is still relatively susceptible. In addition, the B. multivorans isolates were more susceptible in the adult patients than B. cepacia genomovar III isolates. However, it was noted that 81% of the adults were infected with a pan-resistant genomovar III epidemic organism. With the emergence of pan-resistance in BCC organisms, in particular in B. cepacia genomovar III, clinicians are often compromised in choosing combinations of two or more agents in order to obtain a synergic effect, in the absence of any in vitro synergy data. Previous data from North America, where such synergy testing is available on request, have indicated various combinations with limited activity in vitro. 1 In this study, 47% of isolates demonstrated antagonism when a second antibiotic was added, and triple combinations of tobramycin, meropenem and an additional antibiotic were most effective and were bactericidal against 81‐93% of isolates tested. However, no data are available to indicate the in vitro efficacy of these combinations against UK isolates. Recently, Mackay et al. 4 examined a chequerboard method and time‐kill curves to examine antagonism and synergy in seven BCC isolates, and showed synergy by time‐kill curve with a combination of rifampicin and ceftazidime, but were unable to demonstrate antagonism in any of the combinations employed. In conclusion, antimicrobial management of BCC in CF remains a complex problem, and hence some form of synergy testing, especially testing to examine and prevent antagonism, should form a basis to help guide more efficacious combinations of agents used. Development of a UK reference laboratory for antagonism/synergy testing of isolates should be evaluated further to help guide optimal and appropriate therapy in such patients.
TL;DR: 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 and the susceptibility of Escherichia coli was similar in all three areas.
Abstract: 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 SmithKline 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 ≥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.
TL;DR: The susceptibility of 10 Plesiomonas shigelloides strains to 30 beta-lactam antibiotics was examined and revealed a medium-independent inoculum dependency, characterized by a step-to-step correlation between MICs and inocula.
Abstract: The susceptibility of 10 Plesiomonas shigelloides strains to 30 beta-lactam antibiotics was examined. Susceptibility testing was carried out with a microdilution procedure using 3 media (Isosensitest broth, Mueller-Hinton broth and cation-adjusted Mueller-Hinton broth) and 4 inocula [1 x 10(4), 1 x 10(5), 1 x 10(6) and 1 x 10(7) colony-forming units (CFU)/ml]. A high inoculum dependency of MIC values was found for numerous beta-lactams. Each strain showed 2 completely different susceptibility patterns to several cephalosporins and aztreonam, but the same patterns were found with little variation in each strain. Using an inoculum of 1 x 10(4) CFU/ml the strains showed a high susceptibility to aztreonam and to all cephalosporins in all media (pattern 1), whereas they showed a decreased susceptibility to aztreonam and numerous cephalosporins with an inoculum of 1 x 10(7) CFU/ml (pattern 2). Using an inoculum of 1 x 10(6) CFU/ml, 4/10 strains in lsosensitest broth and 2/10 strains in Mueller-Hinton media showed pattern 1. Susceptibility testing of numerous penicillins revealed a medium-independent inoculum dependency, characterized by a step-to-step correlation between MICs and inocula. The beta-lactam susceptibility patterns arising from different inocula point to new beta-lactamase expression and regulation mechanisms in Plesiomonas. The potential to be resistant to a variety of beta-lactams under conceivable testing conditions should question the use of numerous beta-lactams for the treatment of Plesiomonas infections.