scholarly journals Alternative empiric therapy to carbapenems in management of drug resistant gram negative pathogens: a new way to spare carbapenems

2015 ◽  
Vol 3 (1) ◽  
pp. 2 ◽  
Author(s):  
Prashant Bhatia
2020 ◽  
Vol 20 (1) ◽  
pp. 69-75
Author(s):  
Santi M. Mandal ◽  
Subhanil Chakraborty ◽  
Santanu Sahoo ◽  
Smritikona Pyne ◽  
Samaresh Ghosh ◽  
...  

Background: The need for suitable antibacterial agents effective against Multi-drug resistant Gram-negative bacteria is acknowledged globally. The present study was designed to evaluate the possible antibacterial potential of an extracted compound from edible flowers of Moringa oleifera. Methods: Five different solvents were used for preparing dried flower extracts. The most effective extract was subjected to fractionation and further isolation of the active compound with the highest antibacterial effect was obtained using TLC, Column Chromatography and reverse phase- HPLC. Approaches were made for characterization of the isolated compound using FTIR, NMR and Mass spectrometry. Antibacterial activity was evaluated according to the CLSI guidelines. Results: One fraction of aqueous acetic acid extract of M. oleifera flower was found highly effective and more potent than conventional antibiotics of different classes against Multi-drug resistant Gram-negative bacilli (MDR-GNB) when compared. The phytochemical analysis of the isolated compound revealed the presence of hydrogen-bonded amine and hydroxyl groups attributable to unsaturated amides. Conclusion: The present study provided data indicating a potential for use of the flowers extract of M. oleifera in the fight against infections caused by lethal MDR-GNB. Recommendations: Aqueous acetic acid flower extract of M. oleifera is effective, in-vitro, against Gram-negative bacilli. This finding may open a scope in pharmaceutics for the development of new classes of antibiotics.


2013 ◽  
Vol 7 (1) ◽  
pp. 72-82 ◽  
Author(s):  
Marta Martins ◽  
Matthew P McCusker ◽  
Miguel Viveiros ◽  
Isabel Couto ◽  
Séamus Fanning ◽  
...  

It is known that bacteria showing a multi-drug resistance phenotype use several mechanisms to overcome the action of antibiotics. As a result, this phenotype can be a result of several mechanisms or a combination of thereof. The main mechanisms of antibiotic resistance are: mutations in target genes (such as DNA gyrase and topoisomerase IV); over-expression of efflux pumps; changes in the cell envelope; down regulation of membrane porins, and modified lipopolysaccharide component of the outer cell membrane (in the case of Gram-negative bacteria). In addition, adaptation to the environment, such as quorum sensing and biofilm formation can also contribute to bacterial persistence. Due to the rapid emergence and spread of bacterial isolates showing resistance to several classes of antibiotics, methods that can rapidly and efficiently identify isolates whose resistance is due to active efflux have been developed. However, there is still a need for faster and more accurate methodologies. Conventional methods that evaluate bacterial efflux pump activity in liquid systems are available. However, these methods usually use common efflux pump substrates, such as ethidium bromide or radioactive antibiotics and therefore, require specialized instrumentation, which is not available in all laboratories. In this review, we will report the results obtained with the Ethidium Bromide-agar Cartwheel method. This is an easy, instrument-free, agar based method that has been modified to afford the simultaneous evaluation of as many as twelve bacterial strains. Due to its simplicity it can be applied to large collections of bacteria to rapidly screen for multi-drug resistant isolates that show an over-expression of their efflux systems. The principle of the method is simple and relies on the ability of the bacteria to expel a fluorescent molecule that is substrate for most efflux pumps, ethidium bromide. In this approach, the higher the concentration of ethidium bromide required to produce fluorescence of the bacterial mass, the greater the efflux capacity of the bacterial cells. We have tested and applied this method to a large number of Gram-positive and Gram-negative bacteria to detect efflux activity among these multi-drug resistant isolates. The presumptive efflux activity detected by the Ethidium Bromide-agar Cartwheel method was subsequently confirmed by the determination of the minimum inhibitory concentration for several antibiotics in the presence and absence of known efflux pump inhibitors.


2021 ◽  
Vol 10 (Supplement_1) ◽  
pp. S19-S19
Author(s):  
Valentina Gutiérrez ◽  
Ximena Claverie

Abstract Background Fever during neutropenia is a common occurrence in children with cancer. In a systematic review of RCTs of pediatric febrile neutropenia, compared monotherapy with aminoglycoside-containing combination therapy found no significant differences in failure rates, infection-related mortality, or overall mortality. The updated pediatric-specific guidelines recommend initiation of empirical antibiotic monotherapy using an antipseudomonal β-lactam, a fourth-generation cephalosporin, or a carbapenem for pediatric high-risk febrile neutropenia. However, local epidemiology and resistance patterns should be evaluated regularly. Our local hospital epidemiology does not have Pseudomonas aeruginosa isolates, therefore, we used ceftriaxone as monotherapy in patients with high-risk febrile neutropenia without other risk factors. The goal of our investigation is to describe the experience of using third-generation cephalosporins in these patients. Methods Descriptive study of high-risk febrile neutropenia episodes in patients admitted to the Pediatric Oncology Unit of Hospital Dr. Sótero del Río, Santiago, Chile. We included patients ≤15 years from June 2016 until November 2019. Results We found a total of 133 high-risk febrile neutropenia episodes corresponding to 50 patients, 78% were leukemia and 22% were solid tumor patients. Of the 133 episodes, 92 (69%) had clinical signs at admission, mostly respiratory in 46 (50%) of the cases, 18 (29%) had mucositis and 13 (14%) had diarrhea. Of 133 episodes, 41 (31%) did not have any source at clinical examination. Eighty-six (65%) cases started ceftriaxone at admission, 28 (33%) maintained ceftriaxone for 7 days of treatment with good clinical response. Of this group 58 (67%) patients changed treatment: 32 (37%) cases started second-line antibiotics for clinical worsening, 19 (22%) cases required second- and third-line antibiotics for persistent fever and clinical worsening, and 7 (8%) received third-line antibiotics from the start for past microbiological history. Sixteen (12%) cases of total evolved with sepsis requiring intensive care unit management. We had 30 (23%) episodes with positive blood culture, 11 (37%) due to gram-positive bacteria, 16 (53%) gram-negative bacteria, and 3 (10%) cases of fungal infections. Of the gram-negative bacteria, 7 (44%) were ESBL producers, without P. aeruginosa isolates. One case died (0.7%) for refractory sepsis due to gram-negative bacteria. Conclusion Although we did not have P. aeruginosa isolates, due to the spread of ESBL strains, monotherapy with ceftriaxone is not a good option as initial therapy for high-risk febrile neutropenia patients. The empiric therapy has to be evaluated regularly and should always be based on local epidemiology.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S479-S479
Author(s):  
Farah Tanveer ◽  
Dima Youssef ◽  
Mamta Youssef ◽  
Susanna Szpunar ◽  
Michelle Flood

Abstract Background Surgical site infection (SSI) after breast surgery is much more common than expected after a clean surgical procedure. Although breast SSIs are primarily Gram-positive; recent literature shows an increase in Gram-negative infections. We assessed the risk factors and microbiology of SSI following breast surgery at our institution. Methods We conducted a historical cohort study of all (³ 18 y) females who had surgery from 1/1/2014-3/31/2019 and subsequent SSI within 90 days of the procedure. Two controls, matched for surgery type, were selected per case. Data were collected on demographic and clinical characteristics, surgery type, microbiology and antibiotics. Data were analyzed using the χ 2 test, Student’s t-test and multivariable logistic regression with a forward likelihood ratio algorithm. Results After excluding patients with limited data, we reviewed 284 charts: 95 of 132 cases and 189 controls. The 90-day incidence of SSI was 3.5 % (132/3755). Cases were younger than controls: 53.9 ± 12.4 years vs. 58.3± 13.7 years, respectively, p=0.02. Controls had more comorbidities: 1.8 ± 1.3 vs. 1.4 ± 0.7,respectively, p=0.001. Tissue expanders were placed in 65 (70%) cases versus 11 (5.8%) controls (p < 0.0001). After controlling for age, BMI, comorbidities and post-operative antibiotics, only tissue expanders were associated with infection (OR=35.1, p< 0.0001, 95% CI: 16.6, 74.0). Microbiological data were available for 84 cases. Gram-positive organisms accounted for 45 (53.6%) infections and Gram-negative organisms accounted for 39 (46.4%) infections. Over 72% of African Americans (p= 0.014), 76.5% of patients with diabetes (p=0.005) and 57.1 % with tissue expanders (p= 0.02) had Gram-negative infections. The table shows the multivariable predictors of Gram-negative infection. Tissue expander removal was required in 61.5% of patients with Gram-negative infections compared to 39% with Gram-positive infections. Predictors of Gram-negative SSI after breast surgery Conclusion Patients with tissue expanders had a higher incidence of SSI after breast surgery; removal was often required in Gram-negative infections. Diabetes and post-operative antibiotics were significant predictors of Gram-negative infection. Knowledge of local epidemiology is a key factor in deciding empiric therapy for SSI. Disclosures All Authors: No reported disclosures


1998 ◽  
Vol 42 (8) ◽  
pp. 2006-2011 ◽  
Author(s):  
Yoichi Hirakata ◽  
Koichi Izumikawa ◽  
Toshiyuki Yamaguchi ◽  
Hiromu Takemura ◽  
Hironori Tanaka ◽  
...  

Gram-negative rods (GNR) carrying the transferable carbapenem resistance gene blaIMP, includingPseudomonas aeruginosa and Serratia marcescens, have been isolated from more than 20 hospitals in Japan. Although the emergence of such multiple-drug-resistant bacteria is of utmost clinical concern, little information in regard to the distribution ofblaIMP-positive GNR in hospitals and the clinical characteristics of infected patients is available. To address this, a system for the rapid detection of theblaIMP gene with a simple DNA preparation and by enzymatic detection of PCR products was developed. A total of 933 ceftazidime-resistant strains of GNR isolated between 1991 and 1996 at Nagasaki University Hospital, Nagasaki, Japan, were screened for theblaIMP gene; 80 isolates were positive, including 53 P. aeruginosa isolates, 13 other glucose-nonfermenting bacteria, 13 S. marcescens isolates, and 1 Citrobacter freundii isolate. Most of the patients from whom blaIMP-positive organisms were isolated had malignant diseases (53.8%). The organisms caused urinary tract infections, pneumonia, or other infections in 46.3% of the patients, while they were just colonizing the other patients evaluated. It was possible that blaIMP-positive P. aeruginosa strains contributed to the death of four patients, while the other infections caused by GNR carryingblaIMP were not lethal. DNA fingerprinting analysis by pulsed-field gel electrophoresis suggested the cross transmission of strains within the hospital. The isolates were ceftazidime resistant and were frequently resistant to other antibiotics. Although no particular means of pathogenesis ofblaIMP-positive GNR is evident at present, the rapid detection of such strains is necessary to help with infection control practices for the prevention of their dissemination and the transmission of the resistance gene to other pathogenic bacteria.


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