Pandrug-resistant Bacteria Research Articles

Extensively drug-resistant and pandrug-resistant Gram-negative bacteria in a tertiary-care hospital in Eastern India: A 4-year retrospective study

Bacteria resistant to different classes of antimicrobial agents are a major threat to humanity and risk leading the world towards the return of the pre-antimicrobial era. This study was undertaken to detect the incidence of extensively drug-resistant (XDR) and pandrug-resistant (PDR) bacteria in a tertiary-care hospital in Bhubaneswar, Odisha, India. Positive bacterial cultures from different clinical samples were identified using a VITEK®2 compact system and the antimicrobial susceptibility profile of different Gram-negative bacteria was analysed. A total of 2489 clinical samples were collected and processed for culture during the period January 2013 to April 2017. Of 1103 pure bacterial cultures, 690 (62.6%) were Gram-negative bacteria. The antimicrobial susceptibility profile of Gram-negative bacterial strains revealed that 41.3% (n=285) were XDR and 8.1% (n=56) were PDR. Rates of colistin and tigecycline resistance were 16% and 51.9%, respectively. This situation demands regular surveillance of antimicrobial resistance of Gram-negative bacteria and implementation of an efficient infection control programme.

Prevalence of aerobic pathogenic bacteria isolated from patients with burn infection and their antimicrobial susceptibility patterns in Al-Najaf City, Iraq- a three-year cross-sectional study.

Background: Burn infections are one of the most common serious illnesses caused by pathogens, mainly by both gram-negative and gram-positive bacteria. The aim of this study was to detect of the prevalence of multi-drug resistant and extended-spectrum β-lactamase-producing (ESBL) bacteria isolated from inpatients with burn infection and the antimicrobials sensitivity patterns of all bacterial isolates during three years. Methods: This cross-sectional study was performed in Al-Najaf Central Hospital in Al-Najaf City, Iraq from January 2015 to December 2017. A total of 295 burns swabs were collected from hospitalized patients with burn infection. All grown bacterial isolates were identified by standardized microbiological tests. Antimicrobials susceptibility testing was done using the disc diffusion method. Multi-drug, extensive-drug and pan-drug resistant bacteria and extended-spectrum β-lactamase-producing bacteria were determined according to standardized methods and guidelines. Results: Of the 295 burn swabs, 513 different bacteria strains were isolated. Pseudomonas aeruginosa was the most common bacteria with 142 isolates (27.6%) followed by methicillin resistance Staphylococcus aureus 106 isolates (20.6%), while Staphylococcus typhi was the least common bacteria with only 17 isolates (3.3%). 323 (63%) different bacterial strains were isolated from patients who stayed in hospital for 15 days. Most bacterial isolates were resistant to most antimicrobials with high percentages. Out of the 513 bacterial isolates; only 33 isolates (6.4%) were resistant to imipenem 10µg and 464 isolates (90.4%) were multi-drug resistant, 20 isolates (14%) were extensive-drug resistant and 17 isolates (3.3%) were pan-drug resistant. Pseudomonas aeruginosa was the most common ESBL-producing bacteria (51 isolates-35.9%). Conclusions: There was a high prevalence of multi-drug resistant bacteria in burn infection in Al-Najaf hospital. Pseudomonas aeruginosa was the most common multi-drug resistant bacteria, and the most common of ESBL bacteria causing burn infection over the three years.

Clinical Impact and Emerging Multi Drug Resistance of Acinetobacter Baumannii and Pseudomonas Aeruginosa Isolates

Background: Acinetobacter and Pseudomonas are the two most important member of the Non fermenter group. They cause serious life threatening infections. They are mainly nosocomial causing infection in deprived immunity. Multi drug resistance is the major problem which may be intrinsic, or extrinsic. Methods: It was a prospective study done in tertiary care hospital, Surat. All clinical samples were included. Processing of samples, identification of isolates and antibiotic susceptibility were done using standard guidelines. Clinical correlation of the patients was done. Result: Total 151 samples showed growth of Acinetobacter and Pseudomonas. A. Baumannii was the most common isolated followed by P. aeruginosa. Only Polymyxins showed complete sensitivity. Most of the isolates were from surgical and orthopedic wards with trauma as predominant infectious cause. Monomicrobial infections and male preponderance were observed. Most of the patients got discharged within 10 days of admission. Clinical outcome showed 72 % of discharge rate followed by death. Conclusion: The only group having complete sensitivity towards organisms was the Polymyxin group. The most common cause being trauma, strict infection control practices with emphasis on hand hygiene should be followed to prevent emergence of pan drug resistant bacteria.

Incidence of multidrug-resistant, extensively drug-resistant and pan-drug-resistant bacteria in children hospitalized at Dr. Hasan Sadikin general hospital Bandung Indonesia

Antibiotic resistance has become a global issue, with 700,000 deaths attributable to multidrug-resistance (MDR) occurring each year. Centers for Disease Control and Prevention (CDC) show rapidly increasing rates of infection due to antibiotic-resistant bacteria. The aim of the study isto describe the incidence of MDR, extensively drug-resistant (XDR) and pan drug-resistant (PDR) in Enterococcus spp., Staphylococcus aureus, K. pneumonia, Acinetobacter baumanii, P. aeruginosin, and Enterobacter spp. (ESKAPE) pathogens in children admitted to Dr. Hasan Sadikin Hospital. All pediatric patients having blood culture drawn from January 2015 to December 2016 were retrospectively studied. Data include the number of drawn blood culture, number of positive results, type of bacteria, sensitivity pattern. International standard definitions for acquired resistance by ECDC and CDC was used as definitions for MDR, XDR and PDR bacteria. From January 2015 to December 2016, 299 from 2.542 (11.7%) blood culture was positive, with Staphylococcus aureus, Enterococcus spp., Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter spp., respectively 5, 6, 24, 5, 20 with total 60 (20%). The MDR and XDR pathogen found were 47 and 13 patients, respectively.

Complete genome sequencing and genomic characterization of two Escherichia coli strains co-producing MCR-1 and NDM-1 from bloodstream infection

We previously described the discovery of two Escherichia coli isolates (EC1002 and EC2474) co-harbouring mcr-1 and blaNDM-1 genes, which were recovered from bloodstream infection in China. More importantly, these antibiotic resistance genes were located on different plasmids and signaling the potential spread of pandrug-resistant bacteria. Here, the complete genome sequences of both isolates were determined using Pacbio RS II and Illumina HiSeq2000 systems. The genome of EC1002 consists of a 5,177,501 base pair chromosome and four circular plasmids, while the genome of EC2474 consists of a 5,013,813 base pair chromosome and three plasmids. The plasmid replicon type of pEC1002_NDM and pEC2474_NDM were identified as IncA/C2 and IncF, respectively. The genetic environment of blaNDM-1 in this study was similar to blaNDM-carrying plasmids detected in China, although the overall nucleotide identity and query coverage were variable. The plasmid replicon type of pEC1002_MCR and pEC2474_MCR were identified as IncI2 and IncHI2, respectively. Two different genetic strategies for mcr-1 gene spread were observed in this study and blaNDM-1 genes were also found transferred by two different mobile genetic elements in two plasmids. The findings of this study further support that the diversified transfer mechanisms of blaNDM-1 and mcr-1 present in Enterobacteriaceae.

Revisiting Antibiotic Resistance Spreading in Wastewater Treatment Plants - Bacteriophages as a Much Neglected Potential Transmission Vehicle.

The spread of antibiotic resistance is currently a major threat to health that humanity is facing today. Novel multidrug and pandrug resistant bacteria are reported on a yearly basis, while the development of novel antibiotics is lacking. Focus to limit the spread of antibiotic resistance by reducing the usage of antibiotics in health care, veterinary applications, and meat production, have been implemented, limiting the exposure of pathogens to antibiotics, thus lowering the selection of resistant strains. Despite these attempts, the global resistance has increased significantly. A recent area of focus has been to limit the spread of resistance through wastewater treatment plants (WWTPs), serving as huge reservoirs of microbes and resistance genes. While being able to quite efficiently reduce the presence of resistant bacteria entering any of the final products of WWTPs (e.g., effluent water and sludge), the presence of resistance genes in other formats (mobile genetic elements, bacteriophages) has mainly been ignored. Recent data stress the importance of transduction in WWTPs as a mediator of resistance spread. Here we examine the current literature in the role of WWTPs as reservoirs and hotspots of antibiotic resistance with a specific focus on bacteriophages as mediators of genetic exchange.

Disparate Antibiotic Resistance Gene Quantities Revealed across 4 Major Cities in California: A Survey in Drinking Water, Air, and Soil at 24 Public Parks.

Widespread prevalence of multidrug and pandrug-resistant bacteria has prompted substantial concern over the global dissemination of antibiotic resistance genes (ARGs). Environmental compartments can behave as genetic reservoirs and hotspots, wherein resistance genes can accumulate and be laterally transferred to clinically relevant pathogens. In this work, we explore the ARG copy quantities in three environmental media distributed across four cities in California and demonstrate that there exist city-to-city disparities in soil and drinking water ARGs. Statistically significant differences in ARGs were identified in soil, where differences in blaSHV gene copies were the most striking; the highest copy numbers were observed in Bakersfield (6.0 × 10–2 copies/16S-rRNA gene copies and 2.6 × 106 copies/g of soil), followed by San Diego (1.8 × 10–3 copies/16S-rRNA gene copies and 3.0 × 104 copies/g of soil), Fresno (1.8 × 10–5 copies/16S-rRNA gene copies and 8.5 × 102 copies/g of soil), and Los Angeles (5.8 × 10–6 copies/16S-rRNA gene copies and 5.6 × 102 copies/g of soil). In addition, ARG copy numbers in the air, water, and soil of each city are contextualized in relation to globally reported quantities and illustrate that individual genes are not necessarily predictors for the environmental resistome as a whole.

A Risk Assessment of Antibiotic Pan-Drug-Resistance in the UK: Bayesian Analysis of an Expert Elicitation Study.

To inform the UK antimicrobial resistance strategy, a risk assessment was undertaken of the likelihood, over a five-year time-frame, of the emergence and widespread dissemination of pan-drug-resistant (PDR) Gram-negative bacteria that would pose a major public health threat by compromising effective healthcare delivery. Subsequent impact over five- and 20-year time-frames was assessed in terms of morbidity and mortality attributable to PDR Gram-negative bacteraemia. A Bayesian approach, combining available data with expert prior opinion, was used to determine the probability of the emergence, persistence and spread of PDR bacteria. Overall probability was modelled using Monte Carlo simulation. Estimates of impact were also obtained using Bayesian methods. The estimated probability of widespread occurrence of PDR pathogens within five years was 0.2 (95% credibility interval (CrI): 0.07–0.37). Estimated annual numbers of PDR Gram-negative bacteraemias at five and 20 years were 6800 (95% CrI: 400–58,600) and 22,800 (95% CrI: 1500–160,000), respectively; corresponding estimates of excess deaths were 1900 (95% CrI: 0–23,000) and 6400 (95% CrI: 0–64,000). Over 20 years, cumulative estimates indicate 284,000 (95% CrI: 17,000–1,990,000) cases of PDR Gram-negative bacteraemia, leading to an estimated 79,000 (95% CrI: 0–821,000) deaths. This risk assessment reinforces the need for urgent national and international action to tackle antibiotic resistance.

Multidrug-resistant, Extensively drug-resistant and Pandrug-resistant bacteria and antimicrobial therapy in combination.

Bangladesh J Med Microbiol 2015; 9 (2): 1-2

Alterations in Outer Membrane Permeability Favor Drug-Resistant Phenotype of Klebsiella pneumoniae.

The increasing number of infections caused by multidrug-resistant and pandrug-resistant bacteria represents a serious worlwide problem. Drug resistance limits available antimicrobials and can lead to suboptimal treatment of bacterial infections. It can be predicted that resistance to more antimicrobial drugs will be acquired by even more bacteria in the future. Among the distinct resistance strategies, preventing drug entrance to intracellular compartment through modification of membrane permeability (bacterial influx) and active export of compounds to the external environment (bacterial efflux) are of particular importance as they limit the interaction of the drug with its intracellular targets and, consequently, its deleterious effects on the cell. Several current studies have extended our understanding of drug resistance mechanisms associated with altered membrane permeability in gram-negative bacteria. In this study, we propose a summary of resistance mechanisms associated with transport of drugs across bacterial cell envelope exploited by Klebsiella pneumoniae, one of the most common nosocomial infection-causing pathogens. The better understanding of molecular bases of drug transport in/out of the single cell may have consequence for success in antimicrobial therapy of infection caused by drug-resistant Klebsiella.

Should Asymptomatic Bacteriuria Be Systematically Treated in Kidney Transplant Recipients? Results From a Randomized Controlled Trial.

The indication for antimicrobial treatment of asymptomatic bacteriuria (AB) after kidney transplantation (KT) remains controversial. Between January 2011 and December 2013, 112 KT recipients that developed one episode or more of AB beyond the second month after transplantation were included in this open-label trial. Participants were randomized (1:1 ratio) to the treatment group (systematic antimicrobial therapy for all episodes of AB occurring ≤24 mo after transplantation [53 patients]) or control group (no antimicrobial therapy [59 patients]). Systematic screening for AB was performed similarly in both groups. The primary outcome was the occurrence of acute pyelonephritis at 24-mo follow-up. Secondary outcomes included lower urinary tract infection, acute rejection, Clostridium difficile infection, colonization or infection by multidrug-resistant bacteria, graft function and all-cause mortality. There were no differences in the primary outcome in the intention-to-treat population (7.5% [4 of 53] in the treatment group vs. 8.4% [5 of 59] in the control group; odds ratio [OR] 0.88, 95% confidence interval [CI] 0.22-3.47) or the per-protocol population (3.8% [1 of 26] in the treatment group vs. 8.0% [4 of 50] in the control group; OR 0.46, 95% CI 0.05-4.34). Moreover, we found no differences in any of the secondary outcomes. In conclusion, systematic screening and treatment of AB beyond the second month after transplantation provided no apparent benefit among KT recipients (NCT02373085).

Membrane permeabilization of colistin toward pan-drug resistant Gram-negative isolates.

Pan-drug resistant Gram-negative bacteria, being resistant to most available antibiotics, represent a huge threat to the medical community. Colistin is considered the last therapeutic option for patients in hospital settings. Thus, we were concerned in this study to demonstrate the membrane permeabilizing activity of colistin focusing on investigating its efficiency toward those pan-drug resistant isolates which represent a critical situation. We determined the killing dynamics of colistin against pan-drug resistant isolates. The permeability alteration was confirmed by different techniques as: leakage, electron microscopy and construction of an artificial membrane model; liposomes. Moreover, selectivity of colistin against microbial cells was also elucidated. Colistin was proved to be rapid bactericidal against pan-drug resistant isolates. It interacts with the outer bacterial membrane leading to deformation of its outline, pore formation, leakage of internal contents, cell lysis and finally death. Furthermore, variations in membrane composition of eukaryotic and microbial cells provide a key for colistin selectivity toward bacterial cells. Colistin selectively alters membrane permeability of pan-drug resistant isolates which leads to cell lysis. Colistin was proved to be an efficient last line treatment for pan-drug resistant infections which are hard to treat.

Treatment strategies for carbapenem-resistant Enterobacteraceae infections

Carbapenems have been used as thelast linefor treating infections caused by resistant Enterobacteriaceae, however in resent years emergence of carbapenem-resistant Enterobacteriaceae(CRE)have been reported worldwide. CRE often is multi-drug resistant bacteria, extensively drug resistant bacteria or pan-drug resistant bacteria. It is increasing year by year and becoming an important threat to global health. Producing carbapenemases is the main mechanism of its drug resistant.Carbapenemases deactivate carbapenems and most other β-lactam antibiotics and make the patients almost no drug to use. It is reported CRE infections occurred mainly in ICU and the prognosis is poor. At present, there is no optimal treatment method and the antibotics option is very limited. This article introduced the prevalence drug resistant mechanisms and treatment strategies of CRE. Key words: Carbapenem-resistant Enterobacteriaceae; Carbapenemases; Resistant bacteria; Therapy,

Emergence of Colistin Resistant Gram Negative Bacilli, in a Tertiary Care Rural Hospital from Western India

Background: Colistin is one of the last resort of antibiotics used specifically in the treatment of multidrug resistant gram negative bacilli. Though an older class of antibiotic with no use in last four decades, resurgence of colistin use is also causing emergence of colistin resistant gram negative bacilli. Objective: The aim of study was to find prevalence of colistin resistance and antibiotic susceptibility pattern of these colistin resistant strains isolated from different clinical specimens in a tertiary care hospital. Methods: The study included clinical specimens received from wards and Intensive Care Units (ICUs), during January 2015 to December 2015. The specimens were processed by standard method, bacteria were identified by VITEK 2 compact (Biomerieux, France) automation system and antimicrobial susceptibility testing was done with the same system to detect MIC for penicillins, β-lactam/ β-lactamase inhibitor, cephalosporins, carbapenems, aminoglycosides, quinolones, folate inhibitors, glycicyclins and polymixins. Results: Colistin resistance was observed in 9.98% of the clinical isolates. 51.81% of these colistin resistant strains were Pseudomonas spp. Tigecycline (41.50%) showed maximum sensitivity to colistin resistant strains. Conclusion: Colistin resistance (9.98%) found in the study is quite alarming. A restricted and rational use of the colistin is the need of hour. A combination of colistin and tigecycline may be useful to prevent further rise of pan drug resistant bacteria. Keywords: Colistin, MIC, MDR, Antibiotic, Antimicrobial Sensitivity Pattern

重症监护病房泛耐药菌感染的治疗方案分析

重症监护病房泛耐药菌感染的治疗方案分析

Bioactive phthalate from marine Streptomyces ruber EKH2 against virulent fish pathogens

Marine Streptomyces ruber EKH2 isolated from sediments of Bardawil Lake, Egypt, was found as a promising strain for producing bioactive metabolite(s) working against some virulent fish pathogens. Some biochemical and morphological characterizations of marine S. ruber EKH2 were carried out. Cell free culture showed activities against the tested pathogens ranging from 15 to 30mm. Optimized conditions for maximum activities were observed at neutrality and temperature 28°C against the tested strains. Two grams of the ethyl acetate crude extract from 10L culture supernatant was chromatographically separated into three fractions and bioassayed. One major antibacterial compound was separated exhibiting MIC average 12.5μg/ml. Phthalic acid was structurally suggested on the basis of gas chromatography–mass spectrum (GC–MS) and infrared spectrum (IR). Phthalate activities were compared with known standard antibiotics used in fish therapy and found to be superior. A slight toxicity of phthalate against brine shrimp (LC50=2800μg/ml) was observed. Dealing with pan-drug resistant bacteria in fish therapy, this study confirmed that marine S. ruber EKH2 is potentially used for extracting phthalic acid as a novel bioactive and non-toxic agent for treating bacterial fish infections.

Antibiotic resistance analysis in hospitalized elderly patients with lower respiratory tract infection caused by Pseudomonas Aeruginosa

Objective To explore the characterization of antibiotic resistance in hospitalized elderly patients with lower respiratory tract infection caused by Pseudomonas Aeruginosa, and provide scientific basis for clinical ra- tional use of antimicrobial drugs and prevent the emergence of pan-drug resistant bacteria. Methods The drug sensi- tive tests of 347 hospitalized elderly patients with lower respiratory tract infection caused by Pseudomonas Aeruginosa in Shandong provincial hospital affinited to Shandong university from May 2010 to June 2012 were analyzed retrospec- tively. Results The antimicrobial resistance of the 347 cases was rather serious. The resistant rates of ampicillin and cefazolin were both 100.0%. Followed by ampicillin/sulbactam, tobramycin, sulfamethoxazole/trimethoprim, the re- sistant rates were 95.1% ,86.8% and 83.6% respectively. The resistant rate of imipenem has reached 19.6%, and the detection rate of pan-drug bacteria was 4.9%. Conclusion The antibiotic resistance in hospitalized elderly pa- tients with lower respiratory tract infection caused by Pseudomonas Aeruginosa has become more and more serious. In order to prevent the emergence and prevalence of pan-drug resistant bacteria, antibacterial agents should be chosen reasonably according to the results of drug sensitive tests. Key words: Respiratory tract infections ; Pseudomonas Aeruginosa; Cross infection ; Antimicrobial resistance; Aged

Promises and failures of gallium as an antibacterial agent.

Gallium has a long history as a diagnostic and chemotherapeutic agent. The pharmacological properties of Ga(III) rely on chemical mimicry; when Ga(III) is exogenously supplied to living cells it can replace Fe(III) within target molecules, thereby perturbing bacterial metabolism. Ga(III)-induced metabolic distresses are dramatic in fast-growing cells, like bacterial cells. Interest in the antibacterial properties of Ga(III) has been raised by the compelling need for novel drugs to combat multidrug-resistant bacteria and by the shortage of new antibiotic candidates in the pharmaceutical pipeline. Ga(III) activity has been demonstrated, both in vitro and in animal models of infections, on several bacterial pathogens, also including intracellular and biofilm-forming bacteria. Ga(III) activity is affected by iron availability and the metabolic state of the cell, being maximal in iron-poor media and in respiring cells. Synergism between Ga(III) and antibiotics holds promise as last resort therapy for infections sustained by pandrug-resistant bacteria.

Antibioprophylaxie chez les enfants immunodéprimés

Infections are the most common cause of morbidity and mortality in pediatric immunocompromised children. The emergence of pan-drug resistant bacteria is particularly concerning for these patients. The risk of infection can be reduced by educational rules, immunizing these patients and sometimes antibiotic prophylaxis. But the individual level of risk is very difficult to assess. Using antibiotics may lead to adverse effects such as allergic reactions, cross-reactions with other drugs, development of super-infections, pseudomembranous colitis and overall development of antibioticresistant bacterial strains. Recommendations for preventing infections in these patients exist for specific case such as inherited disorder or stem cell transplantation. In others cases it depends on physicians' habits: the increase of bacterial resistance could lead to reduce the prescriptions non evidence based and not included in official guidelines. Pneumococcal and meningococcal vaccinations might change guidelines and habits.

P330 Antibiotic combination therapy and clinical outcome for multidrug-resistant Pseudomonas aeruginosa infections

globally, tigecyclinewas consideredas the last resort to treat pandrugresistant bacteria. Though tigecycline non-susceptible K. pneumoniae isolates have been identified increasingly in recent years, the clinical information regarding bloodstream infection due to tigecycline nonsusceptible K. pneumoniae has never been reported. Objectives: The aim of this cohort study is to investigate the clinical and microbiological characteristics of tigecycline non-susceptible Klebsiella pneumoniae bacteremia in adult patients from a medical center in Taiwan. Methods: Patients with tigecycline non-susceptible K. pneumoniae bacteremia identified by E-test using FDA criteria were analyzed at a medical center in Taiwan between January 2010 and December 2012. Data on clinical features, therapy and outcomes of patients were collected from medical records. Genes for cabapenemases, plasmidic ampC -type, and extended-spectrum b-lactamases (EBSLs) were analyzed by polymerase chain reaction. Antimicrobial susceptibilities and pulsed-field gel electrophoresis (PFGE) results were determined among all the isolates. Results: A total of 36 patients with tigecycline non-susceptible K. pneumoniae bacteremia were identified. 29 patients had nosocomial bacteremia and 4patients had healthcare-associated bacteremia. Only 13 patients had the exposure to tigecycline in the past 30 days. The overall 28-day mortality rate was 36.1%. The MIC50 and MIC90 of tigecycline were 6 and 8mg/L, respectively. 8 isolates were ertapenem non-susceptible K. pneumoniae , including 2 isolates not susceptible to imipenem. 19 isolates were ESBL producers, and DHA-1 was detected in 18 isolates. No carbapenemase was detected among the 36 isolates. PFGE demonstrated that most isolates were epidemiologically unrelated. Conclusion: This study for the first time showed the distinct features of tigecycline non-susceptible K. pneumoniae causing bacteremia and the associated poor prognosis. More studies focusing on the risk factor and the resistance mechanisms of tigecycline non-susceptible K. pneumoniae bacteremia are necessary in Taiwan.