scholarly journals Re-thinking Treatment Strategies for Febrile Neutropenia in Paediatric Oncology Population: A Perspective from a Developing Country

Author(s):  
Vinson James ◽  
Anand Prakash ◽  
Kayur Mehta ◽  
Tarangini Durugappa

Abstract Background: This study was conducted to evaluate the microbiological profile of bacterial isolates in febrile neutropenia in a pediatric oncology unit, thereby, reviewing the use of restricted antibiotics and need for aggressive medical treatment accordingly. Methods: A prospective observational study was conducted in a paediatric haemat-oncology division of a tertiary care teaching hospital in southern India from September 2014 to August 2016. Children with febrile neutropenia were enrolled in the study. Blood cultures were performed using automated system. Cultures from other sites were obtained if needed, based on the clinical profile. Standard antibiotic susceptibility testing was done. Statistical analysis was done using SPSS.Results: One hundred and thirty children were enrolled for the study. Two hundred and fifty episodes of febrile neutropenia were studied. Three hundred and eighty four cultures were sent and 92 (24%) cultures were positive. There were 52.2% gram negative isolates followed 35.8% gram positive isolates, 6.5% fungal isolates and 5.5% poly-microbial cultures. Lactose fermenting gram negative bacteria (29 isolates, 31.5%) were the most frequently isolated in the gram negative group, with Escherichia coli being the most common organism (19 isolates, 20.6%). Amongst gram positive coagulase negative staphylococcus (CONS) was the most common (29%). Escherichia coli and NFGNB had only 36%, 25% sensitivity to ceftazidime respectively. Most gram negative bacteria were found to have better sensitivity to amikacin (mean: 57). There was a higher prevalence of extended spectrum beta lactamase producing organisms. 36 out of 48 GNB were found to be either multi/extremely/pan drug resistant. Escherichia coli and Klebsiella were often drug resistant. Significantly higher mortality was associated with gram negative isolates (61.5%)Conclusions: In view of higher prevalence of gram negative isolates and emergence of multi drug resistance, frequent audits of resistance patterns should guide the choice of antimicrobials in febrile neutropenia management. Our results show the importance of surveillance, monitoring resistance frequencies and identifying risk factors specific to each region. Given that significant mortality is attributed to drug resistant gram negative bacteria, early initiation of appropriate antibiotics to cover for drug resistance is required while formulating empirical antibiotic policies for febrile neutropenia in the oncology units in the developing world.

2020 ◽  
Author(s):  
Vinson James ◽  
Anand Prakash ◽  
Kayur Mehta ◽  
Tarangini Durugappa

Abstract Background: This study was conducted to evaluate the microbiological profile of bacterial isolates in febrile neutropenia in a pediatric oncology unit, thereby, reviewing the use of restricted antibiotics and need for aggressive medical treatment accordingly.Methods: A prospective observational study was conducted in a paediatric haemat-oncology division of a tertiary care teaching hospital in southern India from September 2014 to August 2016. Children with febrile neutropenia were enrolled in the study. Blood cultures were performed using automated system. Cultures from other sites were obtained if needed, based on the clinical profile. Standard antibiotic susceptibility testing was done. Statistical analysis was done using SPSS.Results: One hundred and thirty children were enrolled for the study. Two hundred and fifty episodes of febrile neutropenia were studied. Three hundred and eighty four cultures were sent and 92 (24%) cultures were positive. There were 52.2% gram negative isolates followed 35.8% gram positive isolates, 6.5% fungal isolates and 5.5% poly-microbial cultures. Lactose fermenting gram negative bacteria (29 isolates, 31.5%) were the most frequently isolated in the gram negative group, with Escherichia coli being the most common organism (19 isolates, 20.6%). Amongst gram positive coagulase negative staphylococcus (CONS) was the most common (29%). Escherichia coli and NFGNB had only 36%, 25% sensitivity to ceftazidime respectively. Most gram negative bacteria were found to have better sensitivity to amikacin (mean: 57). There was a higher prevalence of extended spectrum beta lactamase producing organisms. 36 out of 48 GNB were found to be either multi/extremely/pan drug resistant. Escherichia coli and Klebsiella were often drug resistant. Significantly higher mortality was associated with gram negative isolates (61.5%)Conclusions: In view of higher prevalence of gram negative isolates and emergence of multi drug resistance, frequent audits of resistance patterns should guide the choice of antimicrobials in febrile neutropenia management. Our results show the importance of surveillance, monitoring resistance frequencies and identifying risk factors specific to each region. Given that significant mortality is attributed to drug resistant gram negative bacteria, early initiation of appropriate antibiotics to cover for drug resistance is required while formulating empirical antibiotic policies for febrile neutropenia in the oncology units in the developing world.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Vinson James ◽  
Anand Prakash ◽  
Kayur Mehta ◽  
Tarangini Durugappa

Abstract Background This study was conducted to evaluate the microbiological profile of bacterial isolates in febrile neutropenia in a pediatric oncology unit, thereby, reviewing the use of restricted antibiotics and need for aggressive medical treatment accordingly. Methods A prospective observational study was conducted in a paediatric haemat-oncology division of a tertiary care teaching hospital in southern India from September 2014 to August 2016. One hundred and thirty children with febrile neutropenia were enrolled in the study. Blood cultures were performed using automated system. Cultures from other sites were obtained if needed, based on the clinical profile. Standard antibiotic susceptibility testing was done. Statistical analysis was done using SPSS. Results One hundred and thirty children were enrolled for the study. Two hundred and fifty episodes of febrile neutropenia were studied. Three hundred and eighty four cultures were sent and 92 (24%) cultures were positive. There were 48 (52.2%) Gram negative isolates followed by 33 (35.8%) Gram positive isolates, six (6.5%) fungal isolates and five (5.5%) poly-microbial cultures. Lactose fermenting Gram negative bacilli (20 isolates, 31.5%) were the most frequently isolated in the Gram negative group, with Escherichia coli being the most common organism (19 isolates, 20.6%). Amongst the Gram positive coagulase negative staphylococcus was the most common (twenty seven isolates, 29%). Escherichia coli and Non lactose fermenting gram negative bacteria (NFGNB) had only 36, 25% sensitivity to ceftazidime, respectively. Most Gram negative bacilli were found to have better sensitivity to amikacin (mean: 57%). There was a higher prevalence of extended spectrum beta lactamase producing organisms. Pan drug resistance, Extreme drug resistance and Multi drug resistance was found in three, twenty and thirteen Gram negative isolates respectively.Escherichia coli and Klebsiella were often drug resistant. Significantly higher mortality was associated with Gram negative isolates (eight deaths out of the thirteen deaths, 61.5%). Conclusions Our results show the importance of surveillance, monitoring resistance frequencies and identifying risk factors specific to each region. Given that significant mortality is attributed to drug resistant Gram negative bacilli, early initiation of appropriate antibiotics to cover for drug resistance is required while formulating empirical antibiotic policies for febrile neutropenia in the oncology units in the developing world.


Author(s):  
Sulochana Manandhar ◽  
Raphael M. Zellweger ◽  
Nhukesh Maharjan ◽  
Sabina Dongol ◽  
Krishna G. Prajapati ◽  
...  

Abstract Background Multi-drug resistance (MDR) and extensive-drug resistance (XDR) associated with extended-spectrum beta-lactamases (ESBLs) and carbapenemases in Gram-negative bacteria are global public health concerns. Data on circulating antimicrobial resistance (AMR) genes in Gram-negative bacteria and their correlation with MDR and ESBL phenotypes from Nepal is scarce. Methods A retrospective study was performed investigating the distribution of ESBL and carbapenemase genes and their potential association with ESBL and MDR phenotypes in E. coli, Klebsiella spp., Enterobacter spp. and Acinetobacter spp. isolated in a major tertiary hospital in Kathmandu, Nepal, between 2012 and 2018. Results During this period, the hospital isolated 719 E. coli, 532 Klebsiella spp., 520 Enterobacter spp. and 382 Acinetobacter spp.; 1955/2153 (90.1%) of isolates were MDR and half (1080/2153) were ESBL producers. Upon PCR amplification, blaTEM (1281/1771; 72%), blaCTXM-1 (930/1771; 53%) and blaCTXM-8 (419/1771; 24%) were the most prevalent ESBL genes in the enteric bacilli. BlaOXA and blaOXA-51 were the most common blaOXA family genes in the enteric bacilli (918/1771; 25%) and Acinetobacter spp. (218/382; 57%) respectively. Sixteen percent (342/2153) of all isolates and 20% (357/1771) of enteric bacilli harboured blaNDM-1 and blaKPC carbapenemase genes respectively. Of enteric bacilli, Enterobacter spp. was the most frequently positive for blaKPC gene (201/337; 60%). The presence of each blaCTX-M and blaOXA were significantly associated with non-susceptibility to third generation cephalosporins (OR 14.7, p < 0.001 and OR 2.3, p < 0.05, respectively).The presence of each blaTEM, blaCTXM and blaOXA family genes were significantly associated with ESBL positivity (OR 2.96, p < 0.001; OR 14.2, p < 0.001 and OR 1.3, p < 0.05 respectively) and being MDR (OR 1.96, p < 0.001; OR 5.9, p < 0.001 and OR 2.3, p < 0.001 respectively). Conclusions This study documents an alarming level of AMR with high prevalence of MDR ESBL- and carbapenemase-positive ESKAPE microorganisms in our clinical setting. These data suggest a scenario where the clinical management of infected patients is increasingly difficult and requires the use of last-resort antimicrobials, which in turn is likely to intensify the magnitude of global AMR crisis.


2021 ◽  
Author(s):  
Zimeng Hu ◽  
Weiye Chen ◽  
Genglin Guo ◽  
Chen Dong ◽  
Yun Shen ◽  
...  

Abstract Carbapenems, as the “last line of defense” against gram-negative bacteria, are increasingly being challenged by drug-resistant bacteria, especially in Enterobacteriaceae. In this study, a carbapenems resistant gram-negative bacterium, named AH001, was isolated from hospital sewage, and modified Hoge test confirmed this bacterium can produce carbapenemase. Further analysis revealed that this bacterium is multi-drug resistance, which against additional seven antibiotics. Whole-genome sequencing and analysis showed that AH001 could not be classified by existing MLST, and its serotype couldn’t be distinguished among O9, O89 or O168 in O antigen prediction. More attention should be paid to the role of environmental source Escherichia coli in the development and transfer of drug resistance in the hospital environment.


Author(s):  
Amit Bhatia ◽  
Juhi Kalra ◽  
Saurabh Kohli ◽  
Barnali Kakati ◽  
Reshma Kaushik

Background: Antimicrobials are a major class of drugs prescribed in Intensive Care Unit (ICU). Widespread use of empirical antibiotic therapy has facilitated the emergence of drug resistance, since empirical therapy is very often initiated at the outset, even before culture and sensitivity reports are available. The problem of drug resistance is on a rise, therefore, this study was planned to assess the drug resistance and sensitivity patterns of the blood isolates recovered from ICU.Methods: An observational- prospective study was conducted in the Tertiary care teaching hospital over a period of twelve months to assess antibiotic resistance and sensitivity pattern. A total of 104 consecutive patients receiving antibiotics in the ICU and having blood cultures with significant growth were included in the study. Blood sample was collected and after obtaining a culture growth, the identification and antimicrobial sensitivity testing was done.Results: Blood stream infection by Gram-negative bacteria (50.96%) was more common than Gram-positive bacteria (49.04%). Coagulase negative Staphylococci (CoNS) was the predominant single blood culture isolate (35.58%). Klebsiella pneumoniae (13.46%), Escherichia coli (12.50%), Acinetobacter baumannii complex (7.69%) were commonly isolated gram negative organisms. Gram positive isolates were resistant to beta lactams in maximum patients whereas Tigecycline, Linezolid, Daptomycin, Vancomycin, Nitrofurantoin and Teicoplanin were sensitive against them. Common gram negative isolates were sensitive to Colistin and Tigecycline but resistant to most of the antibiotics.Conclusions: A preponderance of gram negative bacteria over gram positive bacteria was noted with a higher degree of resistance to most of the first line antimicrobial agents. 


Gut Pathogens ◽  
2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Deepa Karki ◽  
Binod Dhungel ◽  
Srijana Bhandari ◽  
Anil Kunwar ◽  
Prabhu Raj Joshi ◽  
...  

Abstract Background The prevalence of antimicrobial resistance (AMR) among Gram-negative bacteria is alarmingly high. Reintroduction of colistin as last resort treatment in the infections caused by drug-resistant Gram-negative bacteria has led to the emergence and spread of colistin resistance. This study was designed to determine the prevalence of drug-resistance among beta-lactamase-producing strains of Escherichia coli and Klebsiella pneumoniae, isolated from the clinical specimens received at a tertiary care centre of Kathmandu, Nepal during the period of March to August, 2019. Methods A total of 3216 different clinical samples were processed in the Microbiology laboratory of Kathmandu Model Hospital. Gram-negative isolates (E. coli and K. pneumoniae) were processed for antimicrobial susceptibility test (AST) by using modified Kirby-Bauer disc diffusion method. Drug-resistant isolates were further screened for extended-spectrum beta-lactamase (ESBL), metallo-beta-lactamase (MBL), carbapenemase and K. pneumoniae carbapenemase (KPC) production tests. All the suspected enzyme producers were processed for phenotypic confirmatory tests. Colistin resistance was determined by minimum inhibitory concentration (MIC) using agar dilution method. Colistin resistant strains were further screened for plasmid-mediated mcr-1 gene using conventional polymerase chain reaction (PCR). Results Among the total samples processed, 16.4% (529/3216) samples had bacterial growth. A total of 583 bacterial isolates were recovered from 529 clinical samples. Among the total isolates, 78.0% (455/583) isolates were Gram-negative bacteria. The most predominant isolate among Gram-negatives was E. coli (66.4%; 302/455) and K. pneumoniae isolates were 9% (41/455). In AST, colistin, polymyxin B and tigecycline were the most effective antibiotics. The overall prevalence of multidrug-resistance (MDR) among both of the isolates was 58.0% (199/343). In the ESBL testing, 41.1% (n = 141) isolates were confirmed as ESBL-producers. The prevalence of ESBL-producing E. coli was 43% (130/302) whereas that of K. pneumoniae was 26.8% (11/41). Similarly, 12.5% (43/343) of the total isolates, 10.9% (33/302) of E. coli and 24.3% of (10/41) K. pneumoniae were resistant to carbapenem. Among 43 carbapenem resistant isolates, 30.2% (13/43) and 60.5% (26/43) were KPC and MBL-producers respectively. KPC-producers isolates of E. coli and K. pneumoniae were 33.3% (11/33) and 20% (2/10) respectively. Similarly, 63.6% (21/33) of the E. coli and 50% (5/10) of the K. pneumoniae were MBL-producers. In MIC assay, 2.2% (4/179) of E. coli and 10% (2/20) of K. pneumoniae isolates were confirmed as colistin resistant (MIC ≥ 4 µg/ml). Overall, the prevalence of colistin resistance was 3.1% (6/199) and acquisition of mcr-1 was 16.6% (3/18) among the E. coli isolates. Conclusion High prevalence of drug-resistance in our study is indicative of a deteriorating situation of AMR. Moreover, significant prevalence of resistant enzymes in our study reinforces their roles in the emergence of drug resistance. Resistance to last resort drug (colistin) and the isolation of mcr-1 indicate further urgency in infection management. Therefore, extensive surveillance, formulation and implementation of effective policies, augmentation of diagnostic facilities and incorporation of antibiotic stewardship programs can be some remedies to cope with this global crisis.


2021 ◽  
pp. 67-69
Author(s):  
A.P. More ◽  
J.D. Andhale

Introduction: Infections caused by Gram negative bacteria is major health threat to patients in intensive care units and to patients with some comorbidity. Constant surveillance of drug-resistance among the different bacterial pathogens is important in prevention and management of infections caused by these pathogens. Such type of study also help clinicians to prescribe correct drug regimen to the patients suffering from these infections which may be primary, secondary or nosocomial, reducing the morbidity, mortality and hospitalization period. The present study is undertaken to study the drug susceptibility pattern and its incidence among the different bacterial pathogens isolated from different clinical samples obtained at Tertiary Care Hospital. Materials and Methods: The samples received from different clinical units were subjected to bacteriological investigations using standard microbiological procedures. The isolated pure cultures of bacterial pathogens were subjected to antibiotic susceptibility testing as per the CLSI guidelines of 2016. The data of antibiotic susceptibility of each isolated pathogens were tabulated and prevalence of each drug resistance and multidrug resistance were determined to study the trends of drug resistance among these pathogens. Results: The incidence of infections caused by Gram negative bacteria was found to be 74.67% among all the isolates and that of Gram positive bacterial infections was found to be 25.33% respectively. Esch.coli (37.32%) was the most frequently isolated Gram negative bacterium followed by Ps. aeruginosa, Klebsiella spp., Acinetobacter spp. and Proteus spp.in the descending order among all the isolates of Gram positive and Gram negative isolates. Conclusion: The incidence of infections caused by Gram negative bacteria was higher than those caused by Gram positive bacteria. Esch.coli was the most common pathogen among the Gram negative bacterial isolates whereas Staph.aureus was the most common pathogen among all the Gram positive bacterial isolates. All the bacterial isolates showed 100% multi-drug resistance and the incidence of drug resistance to second generation penicillin and cephalosporins were found to be remarkably higher among all the bacterial isolates.


Author(s):  
Saurav Das ◽  
Santosh Kumar ◽  
Pabitra Bhagowati ◽  
Ashish Kumar Singh

Bacterial antibiotic resistance has become a major global health concern. One of the main reasons for the development of multi-drug resistance properties in bacteria is due to the bacterial efflux pump systems. They are important transport proteins, mainly involved in the removal of toxic substrates like antibiotics from inner cell environment. These pumps are responsible for the intrinsic ability of bacteria to get resistant to the antibiotic. Various types of efflux pumps are present in the Gram-positive and Gram-negative bacteria. Plant-derived products like Capsaicin, Olympicin A, and Indirubicin were found to be inhibitors of an efflux pump in Staphylococcus aureus similarly Ursolic acid derivatives; Daidzein and Lanatoside C were plant-derived inhibitors of an efflux pump in Escherichia coli. In this review detail information have been provided about efflux pump inhibitors that have been found to be effective in the Gram-positive bacteria and Gram-negative bacteria. The aim of this review is to focus on the role of plant-derived compounds as effective efflux pumps inhibitors with reference to mainly Staphylococcus aureus and Escherichia coli.


Author(s):  
Saad Alhumaid ◽  
Abbas Al Mutair ◽  
Zainab Al Alawi ◽  
Ahmad J. Alzahrani ◽  
Mansour Tobaiqy ◽  
...  

Abstract Background Studying time-related changes in susceptible pathogens causing healthcare-associated infections (HAIs) is vital in improving local antimicrobial and infection control practices. Objectives Describe susceptibility patterns to several antimicrobials in gram-positive and gram-negative pathogens isolated from patients causing HAIs at three private tertiary care hospitals in Saudi Arabia over a 5-year period. Methods Data on trends of antimicrobial susceptibility among bacteria causing HAIs events in children and adults at three tertiary private hospitals located in Riyadh and Qassim, Saudi Arabia, were collected retrospectively between 2015 and 2019 using the surveillance data datasets. Results Over a 5-year period, 38,624 pathogens caused 17,539 HAI events in 17,566 patients. About 9450 (53.8%) of patients who suffered HAIs were females and the average age was 41.7 ± 14.3 years (78.1% were adults and 21.9% were children). Gram-negative pathogens were 2.3-times more likely to cause HAIs compared to gram-positive bacteria (71.9% vs. 28.1%). The ranking of causative pathogens in decreasing order was: Escherichia coli (38%), Klebsiella species (15.1%), and Staphylococcus aureus (12.6%). Gram-positive isolates were mostly susceptible to linezolid (91.8%) whereas they were resistant to ampicillin (52.6%), cefoxitin (54.2%), and doxycycline (55.9%). Gram-negative isolates were mostly sensitive to tigecycline (95%) whereas they were resistant to cefotaxime (49.5%) and cefixime (59.6%). During the 5 years, there were relatively stable susceptibility patterns to all tested antimicrobials, except for cefotaxime which shown a susceptibility reduction by 41.4%, among Escherichia coli and Klebsiella species. An increase in the susceptibility of Acinetobacter and Enterobacter and Citrobacter species to all studied antimicrobials was observed except for colistin that had a slight sensitivity reduction in 2019 by 4.3% against Acinetobacter species. However, we noted reduced sensitivity of MRSA, CoNS and Enterococcus species to gentamicin; and increased resistance of MRSA to linezolid and vancomycin. Conclusion The observed increase in susceptibility of gram-positive and gram-negative bacteria to studied antimicrobials is important; however, reduced sensitivity of MRSA, CoNS and Enterococcus species to gentamicin; and increased resistance of MRSA to linezolid and vancomycin is a serious threat and calls for effective antimicrobial stewardship programs.


Children ◽  
2021 ◽  
Vol 8 (6) ◽  
pp. 436
Author(s):  
Giovanni Parente ◽  
Tommaso Gargano ◽  
Stefania Pavia ◽  
Chiara Cordola ◽  
Marzia Vastano ◽  
...  

Pyelonephritis (PN) represents an important cause of morbidity in the pediatric population, especially in uropathic patients. The aim of the study is to demonstrate differences between PNs of uropathic patients and PNs acquired in community in terms of uropathogens involved and antibiotic sensitivity; moreover, to identify a proper empiric therapeutic strategy. A retrospective study was conducted on antibiograms on urine cultures from PNs in vesicoureteral reflux (VUR) patients admitted to pediatric surgery department and from PNs in not VUR patients admitted to Pediatric Emergency Unit between 2010 and 2020. We recorded 58 PNs in 33 patients affected by VUR and 112 PNs in the not VUR group. The mean age of not VUR patients at the PN episode was 1.3 ± 2.6 years (range: 20 days of life–3 years), and almost all the urine cultures, 111 (99.1%), isolated Gram-negative bacteria and rarely, 1 (0.9%), Gram-positive bacteria. The Gram-negative uropathogens isolated were Escherichia coli (97%), Proteus mirabilis (2%), and Klebsiella spp. (1%). The only Gram-positive bacteria isolated was an Enterococcus faecalis. As regards the antibiograms, 96% of not VUR PNs responded to beta-lactams, 99% to aminoglycosides, and 80% to sulfonamides. For the VUR group, mean age was 3.0 years ± 3.0 years (range: 9 days of life–11 years) and mean number of episodes per patient was 2.0 ± 1.0 (range: 1–5); 83% of PNs were by Gram-negatives bacteria vs. 17% by Gram-positive: the most important Gram-negative bacteria were Pseudomonas aeruginosa (44%), Escherichia coli (27%), and Klebsiella spp. (12%), while Enterococcus spp. determined 90% of Gram-positive UTIs. Regimen ampicillin/ceftazidime (success rate: 72.0%) was compared to ampicillin/amikacin (success rate of 83.0%): no statistically significant difference was found (p = 0.09). The pathogens of PNs in uropathic patients are different from those of community-acquired PNs, and clinicians should be aware of their peculiar antibiotic susceptibility. An empiric therapy based on the association ampicillin + ceftazidime is therefore suggested.


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