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Cefepime Tazobactam: A new β lactam/ β lactamase inhibitor combination against ESBL producing gram negative bacilli
S. Sharma,A. Gupta,A. Arora
International Journal of Pharmacy and Biomedical Sciences , 2012,
Abstract: Gram negative bacilli (GNB) continue to be an important cause of health care associated infections. Antimicrobial resistance among these bacilli is increasing on a worldwide basis, especially resistance against β lactam antibiotics due to the development of β lactamase enzymes. Carbapenam which were considered drug of choice are now showing resistance. Thus, β lactamase inhibitors should be investigated as a therapeutic option by combining them with the respective cephalosporins/monobactam. Newer combinations like Cefepime tazobactum can be a possible carbapenem saving strategy for de-escalation as well as upfront usage in hemodynamically stable patients in ICU. The study was conducted for the period of six months from November 2010 to April 2011 in a tertiary care cardiac centre at New Delhi, India. Sensitivity pattern of 1009 gram negative isolates was tested against cefepime tazobactum, cefoperazone sulbactam, piperacillin tazobaztam, meropenem, imipenem. The incidence of ESBL in our studies was found to be 74. 6%. The sensitivity of E.Coli, Klebsiella pneumoniae, Proteus mirabilis to Cefepime tazobactum was 86.03%, 41.5% 95.2% respectively. The results showed significant differences in the sensitivities for these antibiotics. Increasing antimicrobial resistance among gram negative organisms is a growing concern. Among all β lactam inhibitor combinations tested, Cefepime Tazobactam revealed the highest activity against ESBL producing E.coli and Klebsiella pneumoniae. Further studies are needed to evaluate these combinations in clinical settings as they can play important role for the clinicians as viable alternative to carbapenems.
Evaluation of the In Vitro Sensitivity Pattern of Multi-Drug Resistant Gram-Negative Bacilli to Cefepime
N Shayanfar,A Nateghian,S Mortazavi
Iranian Journal of Public Health , 2007,
Abstract: Background: Recent increase in resistance among gram-negative bacteria, particularly in referral centers led to difficulties in medical management of severely ill patients all around the world. Given the economic issues, different epidemiologic status and absence of routine system for susceptibility testing in our setting for new antibiotics including 4th generation cephalosporines, it is an urgent need to evaluate their role in our country. Methods: Various multi-drug resistant (resistant to at least two different representatives from the main groups of commonly used antibiotics including third generation cephalosporines, aminoglycosides and new quinolones) gram-negative bacteria were subcultured again on Muller-Hinton agar. Susceptibility testing was done using disk diffusion method with NCCLS criteria and reported according to the predetermined patterns of resistance, types of organs and site of isolation separately. Results: among 96 samples of MDR gram-negative bacteria, Klebsiella spp, Ecoli, Acinetobacter and pseudomonas spp were dominant. Generalized resistance to all groups was the most common pattern of resistance in our samples, in one third of which, there was sensitivity to forth generation cephalosporines. The best observed response was seen among those bacteria with generalized resistance to third generation cephalosporines and partial resistance to new quinolones. Overall, 36% of isolates were sensitive to Cefepime. Urine culture was the most common site of sampling, still the best sensivety results were observed among those isolates from respiratory site. Conclusion: according to our preliminary study, Cefepime might be used in severe infections of gram-negative origin that show generalized resistance to third generation cephalosporines and partial resistance to new quinolones.
Cefepime restriction improves gram-negative overall resistance patterns in neonatal intensive care unit
Araujo, Orlei Ribeiro de;Silva, Dafne Cardoso Bourguignon da;Diegues, Ana Regina;Arkader, Ronaldo;Cabral, Eloíza Aparecida Ferreira;Afonso, Marta Rodriguez;Louzada, Maria Eduarda;Albertoni, Andréa de Cássia Stéfano;
Brazilian Journal of Infectious Diseases , 2007, DOI: 10.1590/S1413-86702007000200022
Abstract: antibiotic restriction can be useful in maintaining bacterial susceptibility. the objective of this study was verify if restriction of cefepime, the most frequently used cephalosporin in our neonatal intensive care unit (nicu), would ameliorate broad-spectrum susceptibility of gram-negative isolates. nine hundred and ninety-five premature and term newborns were divided into 3 cohorts, according to the prevalence of cefepime use in the unit: group 1 (n=396) comprised patients admitted from january 2002 to december 2003, period in which cefepime was the most used broad-spectrum antibiotic. patients in group 2 (n=349) were admitted when piperacillin/tazobactam replaced cefepime (january to december 2004) and in group 3 (n=250) when cefepime was reintroduced (january to september 2005). meropenem was the alternative third-line antibiotic for all groups. multiresistance was defined as resistance to 2 or more unrelated antibiotics, including necessarily a third or fourth generation cephalosporin, piperacillin/tazobactam or meropenem. statistics involved kruskal-wallis, mann-whitney and logrank tests, kaplan-meier analysis. groups were comparable in length of stay, time of mechanical ventilation, gestational age and birth weight. ninety-eight gram-negative isolates were analyzed. patients were more likely to remain free of multiresistant isolates by kaplan-meier analysis in group 2 when compared to group 1 (p=0.017) and group 3 (p=0.003). there was also a significant difference in meropenem resistance rates. cefepime has a greater propensity to select multiresistant gram-negative pathogens than piperacillin/tazobactam and should not be used extensively in neonatal intensive care.
Antimicrobial resistance patterns among Gram-negative bacilli isolated from patients with nosocomial infections: Disk diffusion versus E-test
Hadadi A,Rasoulinejad M,Maleki Z,Mojtahedzadeh M
Tehran University Medical Journal , 2007,
Abstract: Background: The object of this study was to investigate the antimicrobial resistance pattern among common nosocomial Gram-negative bacilli isolated from patients with nosocomial infections. Methods: From June 2004 to December 2005, 380 isolates of common Gram-negative bacilli (Klebsiella, Pseudomonas, Acinetobacter and E. coli) from 270 patients with nosocomial infections in Sina and Imam Hospitals, Tehran, Iran, were evaluated for susceptibility to Imipenem, Cefepime, Ciprofloxacine, Ceftriaxone and Ceftazidime by Disc diffusion and E-test methods. Results: The most frequent pathogens isolated were Klebsiella spp. (40%), followed by Pseudomonas (28%), Acinetobacter spp. (20%) and E. coli (12%). The most active antibiotic was imipenem (84%). 26% of all isolates were sensitive to Cefepime, 26% to Ciprofloxacin, 20% to Ceftazidime and 10% to Ceftrixone. The susceptibility rates of Klebsiella to Imipenem, cefepime, ciprofloxacin, Ceftazidime and Ceftriaxone were 91, 25, 21, 13 and 7 percent, respectively and 91, 19, 17, 21 and 21 percent, respectively, for E. coli. Among Acineto- bacter spp., the susceptibility rate was 77% for Imipenem and 21% for Ciprofloxacin. Among Pseudomonas spp., 75% of isolates were susceptible to Imipenem and 39% to Ciprofloxacin. The comparison of the resistance status of microorganisms by both Disc diffusion and E-test methods showed a clinically noticeable agreement between these two tests. Conclusions: Since antibiotic resistance among Gram-negative bacilli has increased, enforcement of policy regarding proper antibiotic use is urgently needed in order to delay the development of resistance. Although it is widely accepted that E-test is more accurate in determining the resistance of microorganisms, our study showed that the Disc diffusion test will give the same results in most occasions and is therefore still considered useful in clinical practice.
The Evaluation Of Gram Negative Bacilli Isolated From Inpatiens And Its Antibiotic Resistance  [PDF]
Esen ?ZMEN, Mehmet Faruk GEY?K, Mehmet ULU?, Mustafa Kemal ?ELEN, Salih HO?O?LU, Celal AYAZ
Duzce Universitesi Tip Fakültesi Dergisi , 2010,
Abstract: Aim: Resistance to gram negative bacilli is increasing all over the world. In this study, theresistance of gram negative bacilli, which were isolated from inpatients, was evaluated forselected antibiotics. The aim of this study was to acquire the significant results for empirictherapy.Material and Method: Eight hundered ninety eight strains which were isolated from inpatientswere investigated between May 2003 and April 2005 from clinical speciments at DicleUniversity Hospital, Diyarbakir. The microdiluation test was used to determine for antibioticsresistance.Findings: Escherichia coli (n=282), Enterobacter spp. (n=215), Pseudomonas aeruginosa(n=101), Klebsiella spp. (n=95), Stenotrophomanas maltophilia (n=69) and Acinetobacter spp.(n=52) were the most frequent isolates. The resistance ratio among whole isolates againstceftriaxone was 73%, cefotaxime 68%, ceftazidime 63%, trimetoprim/sulfamethoxazole 60%,ciprofloksasin 51%, amikasin 20%, imipenem 3% and meropenem 2%. The resistance to thethird generation cephalosporins, trimetoprim/sulfamethoxazole and ciprofloxacin was foundhigher than other antibiotics in this study.Results: In conclusion, antimicrobial resistance must be monitored for each hospital for areasonable empirical antibiotic therapy. Surveillance studies might be useful for empiricaltreatment approach.
Quinolones resistance and R-plasmids of some gram negative enteric bacilli
OA Daini, OD Ogbolu, A Ogunledun
African Journal of Clinical and Experimental Microbiology , 2005,
Abstract: Out of the two hundred and sixty bacteria isolates from clinical specimens obtained from different body sites at the University College Hospital Ibadan, 166 belonged to the family of Enterobacteriaceae and Pseudomonaceae. The isolated gram-negative enteric bacilli consist of Escherichia coli (22), Klebsiella species (65), Proteus species (20), Salmonella typhi (2), Pseudomonas aeruginosa (39) and Pseudomonas species (18). Among the antimicrobial agents tested, high resistance was found with ofloxacin 44.0%, followed by pefloxacin 30.1% and ciprofloxacin 21.7%. Ciprofloxacin has the lowest MIC of 2 – 32 μg/ml while ofloxacin has the highest 64 μg/ml. Of the 166 strains, 44 were resistant to most of the antimicrobial agents tested. All the strains that were resistant to any antimicrobial agents were also resistant to ofloxacin. A total of 27 plasmids ranging in molecular sizes from 6.6.kb to 17.4kb were extracted from the resistant strains and grouped into 5 plasmid profiles. Transformation experiment revealed that 59.2% of the resistant strains carried a common R-plasmid of size 10.7kb. Plasmid-mediated resistance to ciprofloxacin and pefloxacin was found. Klebsiella species harboured the highest number of R-plasmids with 8, followed by Pseudomonas aeruginosa with 4. Afr. J. Clin. Exper. Microbiol. Vol.6(1) 2005: 14-20
Beta lactamases mediated resistance amongst gram negative bacilli in burn infection  [PDF]
Nitin Bandekar,Vinodkumar CS, Basavarajappa KG, Prabhakar PJ, Nagaraj P
International Journal of Biological and Medical Research , 2011,
Abstract: Introduction: Burn is one of the most common and devastating forms of trauma. Patients with serious thermal injury require immediate specialized care in order to minimize morbidity and mortality. Significant thermal injuries induce a state of Immuno- suppression, which predisposes infectious complications in burn patients. In burn patient infections arise from multiple sources and infect burn wounds by a variety of micro-organisms. Gram negative bacterial infection results from translocation from colon, further more burn patients are infected by Hospital acquired bacteria by various invasive and non invasive procedures Early diagnosis of microbial infections and screening for mechanism of drug resistance is aimed to institute the appropriate antibacterial therapy and to avoid further complications. Objectives: Beta lactamases are enzymes responsible for the resistance to beta lactam antibiotics. This study is aimed at the detection of various types of beta lactamases present among the gram negative bacilli isolated from burn infection. Methods: patients admitted to burn intensive care unit were included in the study.83 gram negative bacilli were isolated and screened for the presence of extended spectrum beta lactamase, AmpC lactamase, Metallo beta lactamase and confirmed by the respective confirmatory tests. Results: 39.8% produced extended spectrum beta lactamases, 22.9% AmpC beta lactamase and 15.7% strains produced metallo beta lactamases. Pseudomonas aeruginosa was the predominant bacteria producing ESBL and AmpC mediated resistance, whereas Acinetobacter baumannii was the predominant MBL producer. Conclusion: It is important to monitor the bacteriology in burn patients at all time, and understand the changing pattern of bacterial flora, antibiotic susceptibility and bacterial strains spreading in burn ward. Extended-spectrum beta-lactamases is the cause of resistance. After sulbactam added to the third generation of cephalosporins, the beta-lactamases were inhibited, but it lead to increase use of carbapenems leading to emergence of metallo beta lactamase mediated resistance. Hence, screening techniques should be performed routinely to detect these β-lactamase producers so that suitable antimicrobial therapy can be instituted.
Antimicrobial susceptibility patterns of unusual nonfermentative gram-negative bacilli isolated from Latin America: report from the SENTRY Antimicrobial Surveillance Program (1997-2002)
Gales, Ana C;Jones, Ronald N;Andrade, Soraya S;Sader, Helio S;
Memórias do Instituto Oswaldo Cruz , 2005, DOI: 10.1590/S0074-02762005000600011
Abstract: the antimicrobial susceptibility of 176 unusual non-fermentative gram-negative bacilli (nf-gnb) collected from latin america region through the sentry program between 1997 and 2002 was evaluated by broth microdilution according to the national committee for clinical laboratory standards (nccls) recommendations. nearly 74% of the nf-bgn belonged to the following genera/species: burkholderia spp. (83), achromobacter spp. (25), ralstonia pickettii (16), alcaligenes spp. (12), and cryseobacterium spp. (12). generally, trimethoprim/sulfamethoxazole (mic50, < 0.5 μg/ml) was the most potent drug followed by levofloxacin (mic50, 0.5 μg/ml), and gatifloxacin (mic50, 1 μg/ml). the highest susceptibility rates were observed for levofloxacin (78.3%), gatifloxacin (75.6%), and meropenem (72.6%). ceftazidime (mic50, 4 μg/ml; 83.1% susceptible) was the most active b-lactam against b. cepacia. against achromobacter spp. isolates, meropenem (mic50, 0.25 μg/ml; 88% susceptible) was more active than imipenem (mic50, 2 μg/ml). cefepime (mic50, 2 μg/ml; 81.3% susceptible), and imipenem (mic50, 2 μg/ml; 81.3% susceptible) were more active than ceftazidime (mic50, >16 μg/ml; 18.8% susceptible) and meropenem (mic50, 8 μg/ml; 50% susceptible) against ralstonia pickettii. since selection of the most appropriate antimicrobial agents for testing and reporting has not been established by the nccls for many of nf-gnb species, results from large multicenter studies may help to guide the best empiric therapy.
Sensitivity pattern of Gram negative bacteria to the new β-lactam/ β-lactamase inhibitor combination: Cefepime/tazobactam
Abdul Ghafur,Ramasamy Pushparaju,Sarathy Nalini,Krishnamurthy Rajkumar
Journal of Microbiology and Infectious Diseases , 2012,
Abstract: Objectives: Increasing prevalence of carbapenem-resistant Gram negative bacteria has prompted researchers to explorealternative antibiotic options. Different -lactam/ -lactamase inhibitor (BL/BLI) combinations are used in manycountries, as a carbapenem saving strategy. The purpose of our study was to evaluate the sensitivity pattern of cefepime/tazobactam combination in comparison to piperacillin/tazobactam, cefoperazone/sulbactam, cefepime andcarbapenem agents.Materials and methods: We conducted retrospective analysis of the sensitivity pattern of Gram negative bacterialisolates in Apollo Speciality Hospital; a 300 bedded, tertiary care Oncology, Neurosurgical and Orthopaedic Centre inSouth India.Results: Out of the 1003 Gram negative, non-repetitive isolates collected over a period of one year; 60.5% were sensitiveto piperacillin-tazobactam, 46.2% to cefepime, 80.4% to cefepime/tazobactam, 71.3% to cefoperazone-sulbactam,79.1% to imipenem and 78.2% to meropenem. Addition of tazobactam increased the susceptibility of cefepime from46.2% to 80.4% in gram negative isolates in general; from 34.4 to 87.9% in E. coli, from 42.3 to 81.0% to Klebsiella, from72.0 to 81.4% in Pseudomonas and 17.2-54.5% to Acinetobacter.Conclusion: Cefepime/tazobactam provided a better invitro sensitivity profile than other BL-BLI combinations studied.This in vitro data needs to be confirmed by clinical studies. J Microbiol Infect Dis 2012; 2(1): 5-8
The effect of silver nanoparticles on Gram-negative bacilli Resistant to Extended-Spectrum
Doudi M
Medical Laboratory Journal , 2012, DOI: http://www.goums.ac.ir/mljgoums/index.php?slc_lang=en&sid=1
Abstract: Background and objectives: Antibiotic resistant to Antimicrobial agents isone of the most important concerns in hospitals, which can lead toincreased costs, treatment fails and mortality rates. The aim of this studywas identification of Gram-negative bacilli resistant to extended-spectrumβ-lactamase Enzymes (ESBLs) and determination of the effect of silvernanoparticles on them.Materials & Methods: Of 276 clinical samples referred to three hospitalsof Isfahan city, 186 gram negative bacilli were studied. To recognizeESBLs production, the bacilli was assessed by disk diffusion method andconfirmed by DDT and Double Disk approximation Test. The ESBLproducing bacteria were subjected to increasing concentrations (12.5, 25,50,100,200,400 and 500 ppm) of silver nanoparticles, prepared in TehranNano Pars Company, and Inhibitory zone diameter was measured.Results: Of 186 isolates, 140 (%75/3) are gram-negative bacilli producingESBLs and 46 (24.7%) of them without this capability. Most of ESBLsbacteria are belonged to urine infections and the most prevalent bacteriumis Klebsiella pneumonia. All samples are sensitive to the nano silversolution with density of 100 ppm. Enterobacter aerogenes (24 mm) andPseudomonas aeruginosa (23mm) have the greatest Inhibitory zonediameter in the presence of 500 ppm of silver nanoparticles.Conclusion: It seems that silver nanoparticles have inhibitory effect on allstudied gram negative bacilli. The inhibitory effect of silver nanoparticlesagainst ESBL producing Gram negative bacteria is dose depended.Keywords: Gram-negative bacilli, ESBLs, silver nanoparticles
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