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PubMedDate not supplied

Comparative activity of beta-lactam antibiotics against 'intrinsically' ticarcillin-resistant strains of Pseudomonas aeruginosa.

The in vitro activity of piperacillin, cefoperazone, cefsulodin, ceftazidime, aztreonam and imipenem was studied against 44 isolates of Pseudomonas aeruginosa with 'intrinsic' resistance to ticarcillin in comparison with 20 ticarcillin-susceptible strains, by MIC determination and the disk diffusion test. The activity of the antibiotics, imipenem excepted, against the resistant strains was reduced when compared to the susceptible strains. The most significant reduction was found for aztreonam and the least significant for ceftazidime. When considering the breakpoints, all strains were intermediate with aztreonam and cefoperazone, but most of them remained susceptible to ceftazidime, piperacillin and cefsulodin.

Anti-Bacterial Agents↗

PubMed1995

Antimicrobial resistance and prevalence of extended spectrum beta-lactamase among clinical isolates of gram-negative bacteria in Riyadh.

The activity of ciprofloxacin, imipenem and 12 other commonly used antibiotics was evaluated against 106 documented clinical isolates from a medical Intensive Care Unit (ICU). The resistance rates to ceftriaxone, cefotaxime, aztreonam and ceftazidime were 42, 25, 24 and 21%, respectively. Apart from Pseudomonas aeruginosa, all isolates were sensitive to ciprofloxacin and imipenem. Complete cross resistance among tested beta-lactam groups was uniformly evident in Enterobacter cloacae, Citrobacter freundii and P. aeruginosa. On the other hand, penicillins and second generation cephalosporins showed cross resistance among Escherichia coli and Klebseilla pneumoniae isolates. Induction experiments indicate that 70 and 62% of P. aeruginosa and E. cloacae or C. freundii produce class I cephalosporinase, respectively. Among all tested isolates, plasmid mediated extended spectrum beta-lactamase (ESBL) was detected in one isolate of K. pneumoniae. The plasmid mediated beta-lactamase is transferable and inhibited by beta-lactamase inhibitors. The transconjugates not only expressed resistance to extended spectrum beta-lactams and aztreonam but also toward tested aminoglycoside antibiotics, with the exception of gentamicin. The obtained transconjugates conferred high level resistance to ceftazidime and aztreonam but considerably low resistance to ceftriaxone and cefotaxime. The isoelectric point for the extended-spectrum beta-lactamase is 8.2.

Anti-Bacterial Agents↗

PubMed2005

Epidemic and endemic spread of Klebsiella pneumoniae producing SHV-5 beta-lactamase in Dubrava University Hospital, Zagreb, Croatia.

Plasmid-encoded resistance to broad-spectrum cephalosporins and aztreonam is becoming a widespread phenomenon in clinical medicine. These antibiotics are inactivated by an array of different extended-spectrum beta-lactamases (ESBLs) which have evolved by point mutations of parental TEM or SHV beta-lactamases. In a previous study conducted during 1994-1995, SHV-2, SHV-2a and SHV-5 beta-lactamases were found among Klebsiella pneumoniae isolates in Dubrava University Hospital. High prevalence of ESBLs among K. pneumoniae strains in this hospital (20%) required further investigation. In this investigation, beta-lactamases from 42 K. pneumoniae strains collected in 1997 and 15 in 2004 from Dubrava University Hospital, were characterized in order to study the evolution of plasmid-encoded resistance to extended-spectrum cephalosporins and aztreonam in that hospital over a prolonged study period. Susceptibility to antibiotics was determined by disk-diffusion and broth microdilution method. beta-lactamases were characterized by isoelectric focusing, determination of hydrolysis of beta-lactam substrates, polymerase chain reaction and sequencing of bla(SHV) genes. All K. pneumoniae strains and their Escherichia coli transconjugants produced beta-lactamase with an isoelectric point of 8.2. Based on sequencing of bla(SHV) genes enzymes of all transconjugants were identified as SHV-5 beta-lactamase which conferred on the producing isolates high level of ceftazidime and aztreonam resistance. In this study, an outbreak of nosocomial infections caused by SHV-5 producing K. pneumoniae was described in 1997 which evolved to endemic spread of SHV-5 producing K. pneumoniae due to multiple plasmid transfer in the Dubrava University Hospital. The strains from 1997 and 2004 were not clonally related. Hospital hygiene measures should be applied in order to control the spread of epidemic strains through the hospital wards and the consumption of the broad-spectrum cephalosporins needs to be restricted to reduce the selection pressure which enables the proliferation of ESBL producers in hospital.

Anti-Bacterial Agents↗

PubMed2000

Isolation and antibiotic susceptibility of Salmonella, Shigella, and Campylobacter from acute enteric infections in Egypt.

While Campylobacter, Salmonella, and Shigella remain major contributors to acute enteric infections, few studies on these pathogens have been conducted in Egypt. From January 1986 to December 1993, 869 Salmonella, Shigella and Campylobacter strains were isolated from stool specimens from 6,278 patients, presenting to the Abbassia Fever Hospital, Cairo, Egypt, with acute enteric infections. Salmonella predominated, totalling 465 isolates, followed by Shigella with 258 isolates, and Campylobacter with 146 isolates. Of the Shigella isolates, 124 were Shigella flexneri, 49 were S. sonnei, 47 were S. dysenteriae (mainly serotype 1, 2, and 3), and 38 were S. boydii. Campylobacter spp. comprised 92 Campylobacter jejuni and 54 C. coli isolates. Isolation of Salmonella was highest during the months of February-March, June-July, and October-November, while that of Shigella was maximal from July to October. Isolation of Campylobacter increased during May-June and again during August-October. Although Salmonella was sensitive to amikacin, aztreonam, ceftriaxone, and nalidixic acid, it was, however, resistant to erythromycin, streptomycin, ampicillin, chloramphenicol, and tetracycline. Shigella (> 80%) was sensitive to amikacin, ceftriaxone, cephalothin, sulphamethoxazole-trimethoprim (except S. sonnei), aztreonam, and nalidixic acid. Resistance (> 50%) was noted only for ampicillin, chloramphenicol, and tetracycline. C. jejuni and C. coli were resistant to cephalothin, aztreonam, and streptomycin. Some of the above antibiotics were employed to characterize the Egyptian isolates, but did not have any clinical utility in the treatment of diarrhoea. Significant differences (p < 0.05) were observed in the resistance profiles of Shigella and Salmonella between late 1980s and early 1990s. The results suggest the use of fluoroquinolones or a third-generation cephalosporin as an empirical treatment of enteric diseases. However, alternative control strategies, including the aggressive development of broadly protective vaccines, may be more effective approaches to curbing morbidity and mortality due to acute enteric infections.

Adolescent↗

PubMed2001

Comparison of three different methods for the presumptive detection of ESBL production in ceftazidime-resistant strains of Klebsiella pneumoniae.

Twenty-eight (28) strains of ceftazidime-resistant Klebsiella pneumoniae were isolated from blood cultures of in-patients from University Hospital, Kuala Lumpur between March 1995 and August 1996. Three methods were used to detect the production of ESBL enzymes by these strains. These three methods include the double-disc synergy test (DDST), inhibitor-potentiated disc-diffusion test (IPDD) and the E-test ESBL method. All strains could be identified as ESBL producers using the DDST method by a minimum of two beta-lactams and these included either a combination of ceftazidime and ceftriaxone with clavulanate respectively or cefotaxime and aztreonam with clavulanate respectively. Similarly using a combination of either cefotaxime and ceftriaxone with clavulanate or ceftriaxone and aztreonam with clavulanate respectively would have detected all strains as ESBL producers. The IPDD method could also detect for ESBL activity based on combinations of beta-lactam antibiotics with clavulanate respectively. All combinations of beta-lactam antibiotics could detect for ESBL activity in all the strains except a combination of either ceftazidime and aztreonam or cefotaxime and ceftriaxone with clavulanate respectively. The E-Test method using ceftazidime alone and in combination with clavulanate was found to be the most effective method in the presumptive identification of ESBL activity in all the strains.

Ceftazidime↗

PubMed2002

Susceptibility patterns of Escherichia coli: prevalence of multidrug-resistant isolates and extended spectrum beta-lactamase phenotype.

OBJECTIVE: To study Escherichia coli (E. coli) susceptibility, prevalence of multidrug-resistant isolates and possible role of extended spectrum beta-lactamases (ESBL) in E. coli resistance. SETTING: Department of Medicine, Shifa College of Medicine, Islamabad. METHODS: Three hundred and seventy eight E. coli isolates from different sources were identified during six-month period. Susceptibility to various antibiotics was checked using standard methods. Multidrug-resistant isolates were separated. Isolates resistant to cefpodoxime and aztreonam were considered as ESBL phenotype, indicating ESBL production. RESULTS: Most of isolates were resistant to ampicillin and trimethoprim/sulfamethoxazole. Overall resistance to ciprofloxacin, ceftriaxone, cefotaxime and cefpodoxime was 49%, 34%, 36% and 38% respectively. Resistance to fourth generation cephalosporins was lower. Almost all Isolates were sensitive to amikacin, imipenem and tazobactam. Aztreonam resistance was found in 25% isolates. Similar pattern was observed for urinary E. coli isolates; 45% E. coli isolates were found to be multidrug-resistant. Nitrofurantoin showed low-level resistance both to multidrug-resistant as well as urinary isolates. Resistance to both cefpodoxime and aztreonam was found in 25% isolates suggesting ESBL production. CONCLUSION: E. coli resistance in Pakistan is much higher than reported from western literature. Multidrug-resistant isolates, including third generation cephalosporins and quinolones, are very common. ESBL production may contribute to this high level resistance against beta-lactams.

Adolescent↗

PubMed1990

Ecological impact of antimicrobial prophylaxis on intestinal microflora in patients undergoing colorectal surgery.

During recent years the impact of different antimicrobial agents on the intestinal microflora in patients undergoing colorectal surgery has been investigated by our research group. Thus the effects on the microflora by parenteral administration of piperacillin, cefoxitin, cefbuperazone, moxalactam, aztreonam, imipenem, ampicillin + sulbactam, clindamycin, tinidazole, ciprofloxacin and ofloxacin have been studied. Pronounced changes were observed in the aerobic microflora in patients receiving ciprofloxacin and ofloxacin, in the anaerobic microflora in patients receiving clindamycin and tinidazole and in both the aerobic and anaerobic microflora in those patients receiving piperacillin, cefoxitin, cefbuperazone, moxalactam, aztreonam, imipenem and ampicillin + sulbactam. Postoperative infections were observed in patients receiving piperacillin (2), ampicillin + sulbactam (1), cefoxitin (1), aztreonam (3), tinidazole (6), clindamycin (5) and ofloxacin (5). In the patient groups receiving cefbuperazone, moxalactam, imipenem and ciprofloxacin, no postoperative infections occurred.

4-Quinolones↗

PubMed1986

[Urinary infections in patients in the U.S.L. 25 Val di Cornia. Percentage frequency and sensitivity to antibiotics].

In order to estimate the present situation concerning bacterial resistance to a group of widely-used antibiotics, the results of several antibiograms, which were carried out from October 1984 to February 1985 on bacterial stocks isolated from urinary cultures sent to the Laboratory of Clinical Chemistry at the Campiglia Marittima Hospital U.S.L. 25 (Livorno) have been collected. The bacterial species most frequently observed are Gram-negative, namely: Escherichia coli (54%), Proteus (19%), Klebsiella (13%) and Pseudomonas (9%). E. coli turned out to be particularly sensitive to cephotaxim, phosphomicin, nalidixic acid but only slightly to gentamycin. Klebsiella was very sensitive to cephotaxim, gentamycin and amikacin, while Proteus reacted positively against cephotaxim, aztreonam and oxolinic acid. Pseudomonas was resistant to nearly every antibiotic examined, except amikacin and aztreonam. Overall analysis reveals that cephotaxim an aztreonam are the most active on E. coli, Proteus and Klebsiella, while gentamycin is only slightly.

Drug Resistance, Microbial↗

PubMed1996

In vitro susceptibility of 124 Xanthomonas maltophilia (Stenotrophomonas maltophilia) isolates: comparison of the agar dilution method with the E-test and two agar diffusion methods.

The in vitro susceptibility of 124 Xanthomonas maltophilia isolates was tested by four methods: Agar dilution (reference method), E-test, a disk diffusion and a tablet diffusion method. Trimethoprim-sulfamethoxazole had the highest activity against X. maltophilia, followed by a combination of aztreonam-clavulanic acid at different ratios, the ratio 1:1 being the most active with a susceptibility rate of 85% as compared to 2% for aztreonam alone. Addition of the beta-lactamase inhibitor tazobactam to piperacillin enhanced the rate of susceptible isolates from 31% to 53%, Relatively few isolates were susceptible to ciprofloxacin (27%) and gentamicin (9%). Generally, the disk diffusion method had a considerably higher frequency of "very major" discrepancies when compared with the agar dilution method than with the other methods. The susceptibility of X. maltophilia to trimethoprim-sulfamethoxazole and ciprofloxacin could reliably be determined by all the diffusion methods tested, but otherwise the agar dilution method is to be preferred. A standardized and reliable diffusion method for susceptibility testing of X. maltophilia remains to be found. Trimethoprim-sulfamethoxazole must be considered the drug of choice in the treatment of severe X. maltophilia infections. The combination aztreonam-clavulanic acid is promising, but must be proved in a clinical setting.

Anti-Bacterial Agents↗

PubMed2026

Efficacy of the NMIC-150 system in identifying extended-spectrum beta-lactamases in clinical isolates.

Extended-spectrum beta-lactamases (ESBLs) are significant contributors to the growing global crisis of antimicrobial resistance. This study evaluated the performance of the NMIC-150 System for susceptibility testing of third-generation cephalosporins (3GCs) and assessed whether ceftazidime-avibactam and aztreonam-avibactam could identify ESBL-producing carbapenem-resistant Enterobacterales (CREs). A total of 278 non-duplicate clinical isolates (Klebsiella pneumoniae, E. coli, and Proteus mirabilis) were analyzed. Antimicrobial susceptibility was determined using reference broth microdilution (BMD) and the NMIC-150 System. ESBL production was defined as an ≥eight-fold reduction in the minimum inhibitory concentration (MIC) of 3GCs in the presence of clavulanic acid, according to CLSI criteria. Whole-genome sequencing was performed to characterize ESBL and carbapenemase genes among 3GC-resistant isolates. A Random Forest model was used to predict ESBL-producing isolates based on MIC values. The NMIC-150 System demonstrated over 90% categorical and essential agreement with BMD for ceftazidime and ceftriaxone, along with robust predictive performance via Random Forest analysis. These findings suggest that the NMIC-150 System is a reliable platform for 3GC susceptibility testing and that an ≥eight-fold MIC reduction with ceftazidime-avibactam or aztreonam-avibactam may serve as a phenotypic indicator of ESBL production in CRE isolates. In conclusion, the NMIC-150 System shows potential for routine antimicrobial resistance surveillance and may facilitate the rapid identification of ESBL-producing CREs in clinical settings.

Microbial Sensitivity Tests↗

PubMed1984

Hemophilus influenzae type b meningitis in infant rabbits. Pathogenesis and therapy.

A model of human Hemophilus influenzae type b meningitis was developed in infant rabbits infected intranasally. The pathogenesis and course resembled that in human beings; bacteremia was followed by meningitis with a high mortality. Pretreatment of the nasopharyngeal mucosa with 0.5% trypsin or normal saline significantly increased the rate of bacteremia. Death was age related. Intranasal challenge with type f and nontypeable H influenzae was associated with transient bacteremia. Our results suggest that factors on the respiratory tract epithelial cell surface influence colonization and infection with H influenzae type b and confirm the importance of other host and parasite factors. Intravenous aztreonam resulted in a peak CSF concentration that was 6% to 7% of the serum concentration in infected meninges but only 2% to 3% in normal meninges. Aztreonam reduced mortality in established H influenzae type b meningitis from 88% in untreated animals to 9%.

Animals↗

PubMed1997

Treatment of pneumonia in mechanically ventilated trauma patients. Results of a prospective trial.

OBJECTIVES: To determine the efficacy and magnitude of associated adverse effects of 2 different antibiotic regimens for the treatment of pneumonia in intubated surgical patients and to assay and compare blood samples and bronchoalveolar lavage fluid with respect to some host-defense parameters, especially in patients with unilateral pneumonia. DESIGN: Randomized, prospective, unblinded clinical comparison of 2 treatment arms with respect to intent to treat and clinical and microbiologically evaluable patients. SETTING: Six university surgical services in teaching hospitals with modern and well-staffed intensive care units. INTERVENTIONS: The consistency and objectively of the diagnosis of pneumonia was improved by the use of a grid of diagnostic parameters. Aggressive mechanical approaches to pneumonia in intubated surgical patients were supplemented by therapeutic use of aztreonam and vancomycin hydrochloride or combined imipenem and cilastatin sodium. RESULTS: Patients randomized to the aztreonam-vancomycin group were somewhat more ill, fared slightly better, and had fewer serious drug-related side effects than did those treated with imipenem-cilastatin (all P > .05). Immunologic parameters assessed by evaluation of bronchoalveolar lavage fluid showed differences between infected pulmonary lobes and noninfected ones; some changes were also noted in patients who recovered compared with those whose pneumonia persisted or recurred. CONCLUSIONS: Clinical studies of pneumonia in surgical patients need to be stratified to assure comparability, to identify patients in whom treatment is likely to fail, and to display differences between more and less effective therapies. Studies of blood and bronchoalveolar lavage samples showed that certain local and systemic immunologic parameters correlate with clinical status and outcome.

Aztreonam↗

PubMed1986

Antibiotic stability in an implantable pump.

We measured the stability of vancomycin, amikacin, netilmicin, tobramycin, gentamicin, clindamycin, and aztreonam in an implantable drug pump. Two pumps were filled with the antibiotic being tested and were incubated at 37 degrees for 3 weeks. Samples were taken daily. At 3 weeks the pumps were disassembled and examined microscopically for signs of deterioration. If the pumps were intact, bioassays were used to quantitate the biologic activity of each daily antibiotic sample. Vancomycin degraded the pump. Amikacin, netilmicin, tobramycin, gentamicin, clindamycin, and aztreonam had no effect on the pump and maintained their biologic activity over the 3-week period.

Amikacin↗

PubMed1987

Selection and properties of Pseudomonas aeruginosa variants resistant to beta-lactam antibiotics.

The relation between basal and inducible beta-lactamase production and resistance to beta-lactam compounds was studied in five clinical Pseudomonas aeruginosa isolates and their corresponding resistant variants selected in the presence of either piperacillin, ceftazidime or aztreonam. In all wild-type strains enzyme levels were barely detectable in the uninduced state and most beta-lactams, including sulbactam and clavulanic acid, exhibited poor induction potency. Imipenem proved to be the most potent inducer in both these strains and their resistant variants. In the variants selected by either piperacillin or ceftazidime enzyme production amounted to 1.28 units/mg protein of the cell-free supernatants following the addition of beta-lactams as inducers. Additionally, these variants exhibited the phenomenon of "non-specific" induction, i.e. the increase of enzyme production by either a complex nutrient medium or by addition of vitamins. Enzyme production in the aztreonam-resistant variants was identical to that in the wild-type strains with a single exception, where the entire derepression of beta-lactamase production in one of the variants took place. Derepression of the chromosomally mediated enzyme affects the susceptibility to ureidopenicillins more than that to carboxy-penicillins and cephalosporins, whereas the beta-lactamase-independent resistance results in increased resistance to all beta-lactams with the single exception of imipenem.

Anti-Bacterial Agents↗

PubMedDate not supplied

Monobactams and carbapenems for treatment of intraabdominal infections.

During the last decade improved clinical and microbiological methods have resulted in the realization that most intraabdominal infections involve both aerobic and anaerobic bacteria. Papers on the use of different antimicrobial agents directed against the polymicrobial flora of the infected site have been published. In this paper the use of monobactams and carbapenems for treatment of intraabdominal infections is reviewed. The review is based on data published since 1990. Three hundred forty-four patients participated in three trials where aztreonam combined with clindamycin was compared with other antimicrobial agents for treatment of intraabdominal infections. Eighty-six percent of the patients receiving aztreonam plus clindamycin were cured/improved, while 83% of the patients receiving the comparative drugs had favorable outcomes. Eleven trials compared imipenem/cilastatin versus other antimicrobial combinations for therapy of intraabdominal infections. One thousand three hundred seventy-five patients were evaluated in the trials. Eighty percent of patients treated with imipenem/cilastatin had favorable outcomes, while 81% of the patients receiving the comparative drugs were cured/improved. Nine studies including 1,205 patients for evaluation of meropenem versus other antimicrobial agents in the treatment of intraabdominal infections have been published. Cure/improvement was seen in 96% of the patients treated with meropenem and in 91% receiving the comparative drugs. One trial has been published comparing biapenem with imipenem/cilastatin for treatment of intraabdominal infections. Eighty-three patients participated, 65% of the patients in the biapenem group were cured/improved and 68% in the imipenem/cilastatin group.

Abdomen↗

PubMed1997

Cell elongation and septation are two mutually exclusive processes in Escherichia coli.

Bacterial rod morphogenesis was studied in synchronously growing cells of Escherichia coli C600 during the reshaping process that follows the removal of mecillinam, a beta-lactam antibiotic that specifically inhibits lateral wall formation of gram-negative rods and causes transition to coccal shape. Removal of mecillinam after 30 min of action did not affect the timing of subsequent cell division, but removal after 50 min delayed resumption of cell division for approximately one generation time. In order to study the interplay between lateral wall elongation and septum formation in determining and maintaining the bacterial rod shape, we evaluated the effect of re-adding mecillinam or of adding aztreonam (a specific inhibitor of septum formation) at various stages of the reshaping process. We conclude that mecillinam was active only during the reshaping process, while aztreonam was active only later when the cells were close to dividing again. These results provide further evidence for our previous proposal according to which elongation and septation are two alternating and competing events of the cell cycle and are linked to each other to force bacterial rods to grow to a given length.

Amdinocillin↗

PubMed1994

Superiority of aztreonam/clindamycin compared with gentamicin/clindamycin in patients with penetrating abdominal trauma.

There were 73 evaluable patients entered into a prospective, double-blinded trial comparing aztreonam/clindamycin (A/C) to gentamicin/clindamycin (G/C) for the prevention of infection after penetrating abdominal trauma. Aztreonam was administered at a dosage of 2 g every 8 hours and gentamicin at 5 mg/kg for the first 24 hours and then adjusted by serum monitoring to a peak of 6 to 8 micrograms/mL and a trough of less than 2 micrograms/mL; all patients received 900 mg of clindamycin every 8 hours. Patients with colon wounds received 4 days of antibiotics, and the remaining patients received a 24-hour course. Gunshot wounds occurred in 69% of patients: 74% of all patients had some hollow viscus injury, and 26% had only solid viscus injury. The groups were well matched according to abdominal trauma index, percentage with colon injury, and transfusion requirements. Failures occurred in eight patients (11%): two wound infections, five intra-abdominal infections, and one case of necrotizing fasciitis. Seven infections occurred in 36 (19%) G/C patients compared with 1 in 37 (3%) A/C patients (p < 0.03). The hospital stay was 12 +/- 11 days for G/C patients and 8 +/- 7 for A/C patients (p < 0.12). The superiority of the A/C regimen may be partially attributable to relative underdosing of gentamicin (approximately half of the patients had inadequate levels after 24 hours) combined with a favorable pharmacokinetic profile (significantly prolonged half-life) of aztreonam in this clinical setting.

Abdominal Injuries↗

PubMed1990

Penicillin binding proteins of Vibrio cholerae.

Eleven penicillin binding proteins (PBPs) of Vibrio cholerae have been identified using [125I] labelled p-hydroxybenzyl penicillin (PenX). These proteins are localised in the inner membrane and have molecular weights ranging from 97,000 to 22,000. Neutral hydroxylamine released the labelled PenX from the PBPs and pretreatment with cold benzyl penicillin inhibited labelling completely. The PBP 4 is the most sensitive target for cephaloridine and aztreonam. Cephaloridine also binds to three other high molecular weight PBPs, 1, 2 and 3. Aztreonam, in addition to PBP 4, has affinity for another low molecular weight PBP, PBP 7. Mecillinam has affinity for PBPs 1, 4 and 11.

Aztreonam↗