Multidrug-resistant Gram-negative Bacilli Research Articles

Apramycin susceptibility of multidrug-resistant Gram-negative blood culture isolates in five countries in Southeast Asia

IntroductionBloodstream infections (BSIs) are a leading cause of sepsis, which is a life-threatening condition that significantly contributes to the mortality of bacterial infections. Aminoglycoside antibiotics such as gentamicin or amikacin are essential medicines in the treatment of BSIs, but their clinical efficacy is increasingly being compromised by antimicrobial resistance. The aminoglycoside apramycin has demonstrated preclinical efficacy against aminoglycoside-resistant and multidrug-resistant (MDR) Gram-negative bacilli (GNB) and is currently in clinical development for the treatment of critical systemic infections. MethodsThis study collected a panel of 470 MDR GNB isolates from healthcare facilities in Cambodia, Laos, Singapore, Thailand and Vietnam for a multicentre assessment of their antimicrobial susceptibility to apramycin in comparison with other aminoglycosides and colistin by broth microdilution assays. ResultsApramycin and amikacin MICs ≤ 16 µg/mL were found for 462 (98.3%) and 408 (86.8%) GNB isolates, respectively. Susceptibility to gentamicin and tobramycin (MIC ≤ 4 µg/mL) was significantly lower at 122 (26.0%) and 101 (21.5%) susceptible isolates, respectively. Of note, all carbapenem and third-generation cephalosporin-resistant Enterobacterales, all Acinetobacter baumannii and all Pseudomonas aeruginosa isolates tested in this study appeared to be susceptible to apramycin. Of the 65 colistin-resistant isolates tested, four (6.2%) had an apramycin MIC > 16 µg/mL. ConclusionApramycin demonstrated best-in-class activity against a panel of GNB isolates with resistances to other aminoglycosides, carbapenems, third-generation cephalosporins and colistin, warranting continued consideration of apramycin as a drug candidate for the treatment of MDR BSIs.

Antibiotics for multidrug-resistant gram-negative bacteria

Background: Increase in antimicrobial-resistant bacteria continues to be challenge to physicians. Particularly, multidrug-resistant (MDR) gram-negative bacilli (GNB), such as extended-spectrum beta-lactamase (ESBL)-producers and carbapenem-resistant pathogens, are becoming a major human health problem globally.Current Concepts: Gram-negative bacteria have developed resistance via mechanisms encoding AmpC beta-lactamases, ESBLs, and carbapenemases. The therapeutic options available for these pathogens are extremely limited. Infection by MDR bacteria is associated with ineffective antimicrobial therapy, which poses a major threat to the survival of patients with serious infections. Physicians should be familiar with the local epidemiology of MDR bacterial infections and the available therapeutic options. Carbapenems are considered as the drugs of choice for treating ESBL or AmpC-producers. However, increased use of carbapenems in response to an increased prevalence of MDR pathogens could be associated with the rapid emergence of carbapenem resistance. Therefore, there is an ongoing quest for carbapenem-sparing regimens for the treatment of MDR-GNB. Treatment of MDR-GNB infections need not be limited to carbapenems as novel antimicrobial agents are now available.Discussion and Conclusion: This comprehensive review aims to describe therapeutic options available for MDR-GNB infections in Korea, a country with a high prevalence of MDR pathogens. Recently developed antimicrobial agents that should be urgently introduced in Korea include ceftolozane-tazobactam, ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, and cefiderocol. These drugs have been shown to be effective against carbapenem-resistant Enterobacterales, carbapenem-resistant Pseudomonas aeruginosa, and Acinetobacter baumannii.

IN VITRO ACTIVITY OF CEFTAZIDIME-AVIBACTAM AND COLISTIN AGAINST CARBAPENEM-RESISTANT PSEUDOMONAS AERUGINOSA CLINICAL ISOLATES

Objective: Infections caused by multi drug-resistant Gram-negative bacilli are increasingly reported worldwide. Ceftazidime-avibactam is a novel antibiotic combination that presents good activity against carbapenem-resistant Enterobacterales members and Pseudomonas aeruginosa isolates. The objective of this study was to evaluate the in vitro activity of ceftazidime-avibactam and colistin against carbapenem-resistant P. aeruginosa isolates. Materials and Methods: A total of 100 carbapenem-resistant and non-duplicate P. aeruginosa isolates obtained from patient samples in our hospital between 2016-2021 were included in the study. The isolates were identified by MALDI-TOF MS (Bruker Daltonics, Germany). The minimum inhibitory concentration (MIC) values of meropenem, colistin, ceftazidime, and ceftazidime-avibactam were determined by the broth microdilution method. The presence of carbapenemase genes bla KPC, bla NDM, bla OXA-48, bla IMP, and bla VIM were investigated using PCR. Results: Carbapenemase genes were not detected among the isolates except for one isolate producing bla VIM. The susceptibility rates of ceftazidime-avibactam and colistin were 90% (n=90) and 100% (n=100), respectively. The MIC50 and MIC90 values for meropenem, ceftazidime, ceftazidime-avibactam, and colistin against P. aeruginosa isolates were found to be 32/64, 8/64, 4/8, 0.5/2 µg/mL, respectively. Conclusion: The data suggests that ceftazidime-avibactam exhibits as a viable alternative for the treatment of carbapenem-resistant P. aeruginosa isolates. It’s noteworthy that colistin resistance was not detected among the study isolates. Rational use of antibiotics should be emphasized to prevent the development of antibiotic resistance. Surveillance of ceftazidime-avibactam and colistin should be followed up with routine antimicrobial susceptibility tests.

Clinical and microbiological features of obstructive cholangitis with bloodstream infection caused by Pandoraea apista identified by MALDI-TOF mass spectrometry and ribosomal RNA sequencing in a cancer patient

BackgroundPandoraea species are multidrug-resistant glucose-nonfermenting gram-negative bacilli that are usually isolated from patients with cystic fibrosis (CF) and from water and soil. Reports of diseases, including bloodstream infections, caused by Pandoraea spp. in non-CF patients are rare, and the clinical and microbiological characteristics are unclear. The identification of Pandorea spp. is limited by conventional microbiological methods and may be misidentified as other species owing to overlapping biochemical profiles. Here, we report the first case of obstructive cholangitis with bacteremia caused by Pandoraea apista in a patient with advanced colorectal cancer.A 61-year-old man with advanced colorectal cancer who underwent right nephrectomy for renal cell carcinoma 4 years earlier with well-controlled diabetes mellitus was admitted to our hospital with fever for 2 days. The last chemotherapy (regorafenib) was administered approximately 3 weeks ago, and an endoscopic ultrasound-guided hepaticogastrostomy was performed 2 weeks ago under hospitalization for obstructive jaundice. Two days prior, he presented with fever with chills. He was treated with piperacillin-tazobactam for obstructive cholangitis and showed improvement but subsequently presented with exacerbation. Bacterial isolates from the blood and bile samples were identified as P. apista using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and 16S ribosomal RNA sequencing. Based on the susceptibility results of the isolates, he was successfully treated with oral trimethoprim-sulfamethoxazole 160 mg/800 mg/day for 14 days for P. apista infection.ConclusionsPandoraea species are often misidentified. Therefore, multiple approaches should be used to identify them, and decisions regarding antimicrobial treatment should be based on actual in vitro susceptibility. Only seven cases of Pandoraea spp. bloodstream infections have been reported, and we report the first case of cholangitis with bacteremia.

Risk Factors and Outcomes of Acute Graft Pyelonephritis with Bacteremia Due to Multidrug-Resistant Gram-Negative Bacilli among Kidney Transplant Recipients.

Acute graft pyelonephritis (AGP) is the leading cause of bloodstream infection in kidney transplant (KT) recipients. The prevalence of urinary tract infections caused by multidrug-resistant (MDR) Gram-negative bacilli is increasing. This 14-year prospective observational study sought to determine the clinical characteristics, risk factors, and outcomes of AGP with bacteremia due to MDR Gram-negative bacilli. Overall, 278 episodes of AGP with bacteremia due to MDR Gram-negative and non-MDR Gram-negative bacilli were identified and compared in 214 KT recipients; MDR Gram-negative bacilli were the cause in 28.4%. Overall 30-day mortality was low (1.1%). Risk factors independently associated with AGP due to MDR Gram-negative bacilli were male sex (OR 3.08; 95%CI 1.60–5.93), previous episode of bacteremic AGP (OR 2.11, 95%CI 1.09–4.09), prior antibiotic therapy in the preceding month (OR 2.47, 95%CI 1.33–4.57), and nosocomial acquisition (OR 2.03, 95%CI 1.14–3.62). Forty-three percent of MDR Gram-negative episodes received inappropriate empirical antibiotic therapy. The risk factors identified in this study may help physicians when selecting empirical antibiotic treatment for AGP. Previous antibiotic use was the main modifiable factor. Its presence highlights the importance of avoiding unnecessary antibiotics in order to bring down the high rates of MDR Gram-negative bacilli infections in this population.

The clinical impact of errors in semiautomated antimicrobial susceptibility testing of multidrug-resistant Enterobacterales causing bloodstream infections

Appropriate antimicrobial treatment is an important determinant of clinical outcome in patients with severe sepsis and septic shock [1]. Thus, there is a need for rapid identification of pathogens and reliable antimicrobial susceptibility testing (AST) to support therapeutic decision-making. This is particularly relevant in bloodstream infections (BSIs) with multidrug-resistant (MDR) gram-negative bacilli, which are associated with delayed active treatment and poorer clinical outcomes [2].

The role of the microbiology laboratory in the diagnosis of multidrug-resistant Gram-negative bacilli infections. The importance of the determination of resistance mechanisms

Early diagnosis and treatment has an important impact on the morbidity and mortality of infections caused by multidrug-resistant bacteria. Multidrug-resistant gram-negative bacilli (MR-GNB) constitute the main current threat in hospitals and especially in intensive care units (ICU). The role of the microbiology laboratory is essential in providing a rapid and effective response. This review updates the microbiology laboratory procedures for the rapid detection of BGN-MR and its resistance determinants. The role of the laboratory in the surveillance and control of outbreaks caused by these bacteria, including typing techniques, is also studied. The importance of providing standardized resistance maps that allow knowing the epidemiological situation of the different units is emphasized. Finally, the importance of effective communication systems for the transmission of results and decision making in the management of patients infected by BGN-MR is reviewed.

Multidrug-Resistant and Virulent Organisms Trauma Infections: Trauma Infectious Disease Outcomes Study Initiative.

During the wars in Iraq and Afghanistan, increased incidence of multidrug-resistant (MDR) organisms, as well as polymicrobial wounds and infections, complicated the management of combat trauma-related infections. Multidrug resistance and wound microbiology are a research focus of the Trauma Infectious Disease Outcomes Study (TIDOS), an Infectious Disease Clinical Research Program, Uniformed Services University, research protocol. To conduct comprehensive microbiological research with the goal of improving the understanding of the complicated etiology of wound infections, the TIDOS MDR and Virulent Organisms Trauma Infections Initiative (MDR/VO Initiative) was established as a collaborative effort with the Brooke Army Medical Center, Naval Medical Research Center, U.S. Army Institute of Surgical Research, and Walter Reed Army Institute of Research. We provide a review of the TIDOS MDR/VO Initiative and summarize published findings. Antagonism and biofilm formation of commonly isolated wound bacteria (e.g., ESKAPE pathogens-Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.), antimicrobial susceptibility patterns, and clinical outcomes are being examined. Isolates collected from admission surveillance swabs, as part of infection control policy, and clinical infection workups were retained in the TIDOS Microbiological Repository and associated clinical data in the TIDOS database. Over the TIDOS study period (June 2009 to December 2014), more than 8,300 colonizing and infecting isolates were collected from military personnel injured with nearly one-third of isolates classified as MDR. At admission to participating U.S. military hospitals, 12% of wounded warriors were colonized with MDR Gram-negative bacilli. Furthermore, 27% of 913 combat casualties with ≥1 infection during their trauma hospitalization had MDR Gram-negative bacterial infections. Among 335 confirmed combat-related extremity wound infections (2009-2012), 61% were polymicrobial and comprised various combinations of Gram-negative and Gram-positive bacteria, yeast, fungi, and anaerobes. Escherichia coli was the most common Gram-negative bacilli isolated from clinical workups, as well as the most common colonizing MDR secondary to extended-spectrum β-lactamase resistance. Assessment of 479 E. coli isolates collected from wounded warriors found 188 pulsed-field types (PFTs) from colonizing isolates and 54 PFTs from infecting isolates without significant overlap across combat theaters, military hospitals, and study years. A minority of patients with colonizing E. coli isolates developed subsequent infections with the same E. coli strain. Enterococcus spp. were most commonly isolated from polymicrobial wound infections (53% of 204 polymicrobial cultures). Patients with Enterococcus infections were severely injured with a high proportion of lower extremity amputations and genitourinary injuries. Approximately 65% of polymicrobial Enterococcus infections had other ESKAPE organisms isolated. As biofilms have been suggested as a cause of delayed wound healing, wound infections with persistent recovery of bacteria (isolates of same organism collected ≥14 days apart) and nonrecurrent bacterial isolates were assessed. Biofilm production was significantly associated with recurrent bacteria isolation (97% vs. 59% with nonrecurrent isolates; P < 0.001); however, further analysis is needed to confirm biofilm formation as a predictor of persistent wound infections. The TIDOS MDR/VO Initiative provides comprehensive and detailed data of major microbial threats associated with combat-related wound infections to further the understanding of wound etiology and potentially identify infectious disease countermeasures, which may lead to improvements in combat casualty care.

In Vitro Activity of Ceftazidime-avibactam and Colistin Against Carbapenem-Resistant Klebsiella pneumoniae Clinical Isolates

Infections caused by multi drug-resistant gram-negative bacilli are increasingly reported worldwide. Colistin, tigecycline and aminoglycosides are almost the only and last choice antibiotics in the treatment of infections caused by carbapenem-resistant Enterobacterales members. Ceftazidime-avibactam is a novel antibiotic combination consisting of a broad-spectrum cephalosporin and avibactam with good antimicrobial activity against carbapenem-resistant Enterobacterales members. The aim of this study was to assess the in vitro activity of ceftazidime-avibactam and colistin against carbapenem-resistant Klebsiella pneumoniae isolates and to obtain local antimicrobial surveillance data. A total of 150 carbapenem-resistant K.pneumoniae isolates obtained from various clinical samples of the patients hospitalized in our hospital between 2018-2021 were included in the study. Duplicate isolates were excluded from the study. The isolates were recovered from blood (n= 72), tracheal aspirate (n= 40), wound (n= 20), biopsy and abscess (n= 10), steril body fluid (n= 5), and peripheral venous catheter (n= 3) samples. Isolates were identified by matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS, Bruker Daltonics, Germany). The minimum inhibitory concentration (MIC) values of the isolates for meropenem, colistin, ceftazidime, and ceftazidime-avibactam were determined by broth microdilution method. Susceptibility of the isolates to the tested antibiotics was evaluated by the European Committee of Antimicrobial Susceptibility Testing (EUCAST) criteria. The presence of carbapenemases (VIM, IMP, NDM, KPC, and OXA-48) was investigated by polymerase chain reaction (PCR) using specific primers. The mcr-1, mcr-2, mcr-3, mcr-4, and mcr-5 genes were evaluated by PCR for plasmid-mediated colistin resistance. All K.pneumoniae isolates were found to be positive for at least one of the carbapenemase genes evaluated in the study. The blaOXA-48 gene was detected in 107 (71.3%), blaKPC gene in 25 (16.7%); blaNDM gene in 7 (4.7%), co-production of blaOXA-48 and blaKPC genes in 10 (6.7%), co-production of blaOXA-48 and blaNDM genes in 1 (0.6%) isolate. None of the isolates harbored the blaVIM and blaIMP genes. None of the mcr genes screened in the study were detected among the isolates. The susceptibility of the isolates to ceftazidime-avibactam and colistin was 92.7% (139/150) and 48% (72/150), respectively. The MIC50 and MIC90 values for meropenem, ceftazidime, ceftazidime-avibactam, and colistin of the isolates were determined as 32/256, > 128/> 128, 1/8, and 4/16 µg/ml, respectively. Of the ceftazidimeavibactam resistant isolates, seven were positive for blaNDM, three for blaKPC, and one for both blaOXA-48 and blaNDM genes. High ceftazidime-avibactam MIC levels (> 128 µg/ml) were detected in metallo-betalactamase producing isolates. Consequently, our data suggested that ceftazidime-avibactam exhibited as a good alternative therapeutic choice for carbapenem-resistant K.pneumoniae isolates. It is noteworthy that high rate of colistin resistance was detected in K.pneumoniae isolates. Another notable finding of this study is the increase in K.pneumoniae isolates producing blaKPC for our country. To prevent the development of resistance which is observed even in last-choice therapeutic antibiotics, the principles of rational antibiotic use should be followed. The appropriate antimicrobial susceptibility testing should be routinely performed for surveillance of ceftazidime-avibactam and colistin.

The Use of Resapolymyxin NP Test in Determining the Sensitivity of Colistin in Escherichia coli, and Klebsiella pneumoniae Isolates

Colistin is used as the last choice of drug in multidrug resistant gram-negative bacilli infections; therefore, accurate detection of colistin susceptibility has gained critical importance. Unfortunately, many of the widely used and practical methods in the clinical laboratory have various limitations for the determination of colistin susceptibility. This situation has led researchers to search for new methods to determine colistin susceptibility. In this study, the performance of the ResaPolymyxin NP test, which was developed for the rapid detection of colistin susceptibility of Pseudomonas aeruginosa and Acinetobacter baumannii isolates, was evaluated for various Gram-negative bacteria for the determination of colistin susceptibility. For this purpose, the colistin MIC values of 105 Escherichia coli, and 196 Klebsiella pneumoniae isolates were determined by broth microdilution (BMD) using cation-adjusted Mueller-Hinton broth and then ResaPolymyxin NP test was applied for each isolate. While 242 (%80.4) of the isolates included in the study were found to be susceptible to colistin with BMD, 214 (71.1%) of the isolates were found as sensitive to colistin with the ResaPolymyxin NP test. The categorical agreement rate for the ResaPolymyxin NP test was 85.7% for E.coli isolates, and 92.3% for K.pneumoniae isolates. The major error rate was 14.7% for E.coli, 10.8% for K.pneumoniae, whereas the very major error rate was 1.8% for K.pneumoniae. For ResaPolymyxin NP test, sensitivity, specificity, positive and negative predictive values were %98,3; %88.0; %66.7; and %99.5. In contrast to the available data about the ResaPolymyxin NP test, both the categorical agreement rate with BMD, and the very major and major error rates varied according to the isolate type, and it was concluded that the test performed relatively better in E.coli and K.pneumoniae isolates. Since the data obtained in this study are quite different from the previously published data, more comprehensive and multicenter studies are needed to evaluate the test effectiveness in order to recommend the use of the ResaPolymyxin NP test in clinical microbiology laboratories.

Bacteriological aspects and risk factors for the acquisition of ESBL producing Enterobacteriaceae in urinary tract infections in the elderly

Aim. Our study aimed to know the antibiotic resistance of the isolated strains, as well as the risk factors for acquiring extended-spectrum betalactamase-producing Enterobacteriaceae, in the urinary tract infection of the elderly. Methods. All the urine specimens received from elderly people at the Microbiology Laboratory of Batna Hospital, Algeria, from March 2012 to March 2014 were included in a prospective observational study. The bacteria were identified by API gallery or mass spectrometry. The antimicrobial susceptibility testing was performed as per CLSI guidelines. Multi-drug resistant gramnegative bacilli were studied by PCR and sequencing to determine their resistance mechanisms. The risk factors for ESBL-E acquisition were determined by univariate analysis. Results. From a total of 1024 urinary specimens, 372 microorganisms were isolated. The resistance rates of the community Escherichia coli strains to amoxicillin-clavulanic acid (51.2%) and ciprofloxacin (26.5%) were high. In Enterobacteriaceae, ESBL (11.4%) were all of the CTX-M type, mainly the CTX-M-15 variant, often associated with the qnrB gene. The CTX-M-1 type predominated in E. coli. The carbapenemases produced by non-fermenting bacilli were of the oxacillinase-23 and VIM types while none were produced by Enterobacteriaceae. A recent history of surgery and antibiotic treatment were the main risk factors identified in the ESBL-E acquisition. Conclusion. This study is the first to describe the antibiotic resistance of UTI strains in the elderly in Algeria. Risk factors identified in the acquisition of resistant uropathogens highlight the importance of good hygiene practices and antimicrobial prescription.

Cefiderocol: a novel siderophore cephalosporin against multi-drug resistant Gram-negative bacilli infections

Antimicrobial resistance is one of the critical public health issues in the world. There is an urgent need to develop effective broad-spectrum antibiotics to treat the infection of multi-drug resistant Gram-negative bacilli. Cefiderocol, developed by the Shionogi Inc. in Japan, is a new type of iron carrier cephalosporin antibiotics, which overcomes the drug resistance of Gram-negative bacilli due to the down-regulation of outer membrane pore protein and the up-regulation of efflux pump, and has good stability to serine- and metallo-carbapenemases. This drug has a broad spectrum and strong antibacterial activity against carbapenem-resistant Enterobacteriaceae (CRE), Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia. Cefiderocol can be used to treat complex urinary tract infections (including pyelonephritis), hospital-acquired pneumonia, and ventilator-associated pneumonia. By summarizing the chemical structure, antibacterial mechanism, in vitro antibacterial activity, pharmacokinetics, pharmacodynamics, and clinical treatment of cefiderocol, this review shows the application potential of cefiderocol as a new iron carrier cephalosporin in the treatment of multi-drug resistant Gram-negative bacilli infections.

High prevalence of colistin resistance and mcr-9/10 genes in Enterobacter spp. in a tertiary hospital over a decade

Enterobacter spp. are members of the 'ESKAPE' group of pathogens, which which are recognised as the leading cause of multidrug-resistant (MDR) hospital-acquired infections. Colistin is usually regarded as a last-line therapeutic option for MDR Gram-negative bacilli infections. However, colistin-resistant Enterobacter spp. have emerged in the last decade. Here we investigated the prevalence of colistin resistance and mcr genes in Enterobacter spp. of clinical origin between 2011 and 2020 in a tertiary hospital in China. Colistin resistance rates ranged between 17.1% and 34.5%, with an overall prevalence of 22.2% (190/854). No mcr-1 to mcr-8 genes were identified in the colistin-resistant Enterobacter spp. isolates, while mcr-9 and mcr-10 were detected at rates of 8.4% (16/190) and 12.6% (24/190), respectively. All of the mcr-9/10-positive Enterobacter isolates belonged to the Enterobacter cloacae complex (ECC). Meanwhile, 14.8% (98/664) and 6.0% (40/664) of non-colistin-resistant Enterobacter spp. isolates carried mcr-9 and mcr-10 genes, respectively. For the 40 mcr-9/10-positive colistin-resistant ECC isolates, mcr-9-positive ECC isolates usually co-produced extended-spectrum β-lactamases (ESBLs) or carbapenemases, while mcr-10-positive ECC isolates produced neither. Most mcr-9/10 genes were located on plasmids. The backbone of mcr-9-harbouring plasmids was conserved, while that of mcr-10-harbouring plasmids was diverse. Our findings revealed a high prevalence of colistin resistance and a silent distribution of mcr-9/10 genes in clinical Enterobacter spp. isolates in China. It is urgent to take steps and interventions to control the prevalence of colistin resistance and prevent the dissemination of mcr-9/10 genes.

PREVALENCE OF METALLO-?-LACTAMASE RESISTANT GRAM-NEGATIVE BACILLI IN BENIN CITY, NIGERIA

Detection of metallo-?-lactamase (MBL) is crucial in the management and control of difficult to treat infections. This study aims to determine the prevalence of MBL – producing Gram-negative bacilli among imipenem-resistant multi-drug resistant (MDR) clinical isolates. A total of 224 consecutive MDR Gram-negative bacilli consisting of Escherichia coli (78), Klebsiella species (64), Proteus species (40) and Pseudomonas aeruginosa (40) were used for this study. Imipenem disc susceptibility test was performed on all isolates and MBL detection was performed on imipenem-resistant isolates using standard techniques. Of the 224 MDR isolates tested, 37 (16.52%) were imipenem resistant and the prevalence of this resistant isolates was significantly higher in Ps. aeruginosa (35.00%) compared to others (P = 0.005). Among, the imipenem-resistant isolates, the prevalence of MBL production was highest in Ps. aeruginosa (14.29%) followed by Escherichia coli (11.11%), Klebsiella species (10.00%) and Proteus species (0%). However, the difference in prevalence was not statistically significant (P = 0.8807). Conclusively, Ps. aeruginosa was the most prevalent microorganism that was resistant to imipenem. An overall prevalence of 10.81% of MBL producers was observed among imipenem-resistant microbial isolates. Measures to control and prevent the spread of MBL producing and imipenem-resistant microbial isolates are advocated.

Multidrug resistant Gram-negative bacilli infection in critically ill patients with Coronavirus disease 2019

PurposeRapid spread of multidrug resistant Gram-negative bacilli (MDR-GNB) infection in Coronavirus disease (COVID-19) critically ill patients was observed even in those without underlying diseases and in all age groups. We conducted a prospective cohort study to assess the risk factors for acquisition of MDR-GNB infection in COVID-19 patients and its impact on patients´ outcome.Methods & MaterialsWe included 43 consecutive patients with COVID-19 from a total of 8874 patients with COVID-19 admitted into the ICU of Aleman Hospital, Argentina, from May 1st 2020 to June 30th 2021. Followed up until death or 30 days after hospital discharge. We divided them into 4 groups: colonized with MDR-GNB (G1), colonized with MDR-GNB and infected with non-carbapenem resistant bacteria (G2), colonized and infected with MDR-GNB (G3), and infected with MDR-GNB without previous colonization (G4). Microbiological sampling was performed according to patient's conditions or epidemiological surveillance. Outcomes considered were length of hospital stay (LOS), mortality and readmission rate.ResultsSeven, five, six and twenty five patients were distributed respectively in G1, G2, G3 and G4. Male/female ratio was 2:1 with a median age of 68 years (IQR 62–75). Chronic pulmonary disease (18.6%) was the main comorbidity. Mean LOS was 40.16 days (P=0.79). Prolonged biomedical devices used were observed in 93% of patients (P=0.33). Ventilator associated pneumonia (n:15/36) and catheter-related bloodstream infection (n:16/36) were the most frequent infections (P=0.29, P=0.69). The most common carbapenem-resistant pathogens were Klebsiella pneumoniae (n: 38/60) and Pseudomonas aeruginosa (n:8/60). All patients were exposed to antibiotics before MDR-GNB was diagnosed. The first isolation of MDR-GNB was on average 14 days after hospital admission (P=0,84). Time between MDR-GNB colonization and infection was twice as much between G2 and G3 (8.4 Vs. 4 days, P=0.83). We observed no difference in all-cause mortality rate and readmission rate between the groups (P=0.75, P=0.97).ConclusionProlonged ICU hospitalizations in addition to use of invasive devices and antibiotics exposure correlate with a higher risk of developing MDR-GNB colonization and infection in COVID-19 critically ill patients.

IDSA guidance and ESCMID guidelines: complementary approaches toward a care standard for MDR Gram-negative infections

Antimicrobial resistance continues to pose a major global threat [ [1] Tacconelli E. Carrara E. Savoldi A. Harbarth S. Mendelson M. Monnet D.L. et al. Discovery, research, and development of new antibiotics: The WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis. 2018; 18: 318-327 Google Scholar ]. In response, a number of new antibiotics have been developed and approved for use over the last few years. However, more often than not, the clinical trial evidence base supporting these new drugs has only cursorily involved the treatment of infections due to multidrug resistant (MDR) pathogens [ [2] de Kraker M.E.A. Sommer H. de Velde F. Gravestock I. Weiss E. McAleenan A. et al. Optimizing the design and analysis of clinical trials for antibacterials against multidrug-resistant organisms: A white paper from COMBACTE's STAT-Net. Clin Infect Dis. 2018; 67: 1922-1931 Google Scholar ]. As such, clinicians treating complex MDR Gram-negative infections have to decide between using potentially toxic, yet time-honoured agents and newer, potentially safer agents substantiated by less generalizable evidence. In response to this problem, an expert panel of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) was convened to complete a systematic review of the published literature and compile a practice guideline to support clinicians in the selection of appropriate antimicrobial regimens against commonly encountered MDR Gram-negative pathogens. European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines for the treatment of infections caused by multidrug-resistant Gram-negative bacilli (endorsed by European society of intensive care medicine)Clinical Microbiology and InfectionVol. 28Issue 4PreviewThese ESCMID guidelines address the targeted antibiotic treatment of third-generation cephalosporin-resistant Enterobacterales (3GCephRE) and carbapenem-resistant Gram-negative bacteria, focusing on the effectiveness of individual antibiotics and on combination versus monotherapy. Full-Text PDF

Colistin disposition in the cerebrospinal fluid when administered either intravenously alone or with intraventricular/intrathecally in neonates/pediatric patients with culture-proven meningitis

Nosocomial infections due to cerebrospinal fluid (CSF) in Gram-negative organisms are serious problems in low and middle-income countries (LMIC), involving the central nervous system (CNS) with presentation as either meningitis, ventriculitis, or even abscesses.1 The most common organisms responsible for these infections are multi-drug resistant Gram-negative bacilli, such as Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli, and Klebsiella pneumonia.2

Trends of antimicrobial resistance in patients with complicated urinary tract infection: Suggested empirical therapy and lessons learned from a retrospective observational study in Oman.

Complicated urinary tract infection (cUTI) is defined as an infection associated with structural, functional, or metabolic abnormalities of the genitourinary tract. These infections are caused frequently by multidrug-resistant Gram-negative bacilli. The rapid emergence of extended-spectrum beta-lactamase (ESBL), AmpC, and carbapenemase (CR) producers has made the treatment of such infections increasingly more challenging. The aims of the present study were threefold: to assess the clinical profile, trends in etiology, and antimicrobial susceptibility profile in cUTI over the past 10 years at a tertiary care center in Oman as an interrupted time series on the one hand and to develop guidelines for empirical management of such cases on the other. We conducted a retrospective analysis of cUTI in patients presenting at Sultan Qaboos University Hospital over 3 years (2008, 2013, and 2018) covering a span of 10 years. Data were obtained from the patient's electronic records in the hospital information system. Analysis was done using the Statistical Package for Social Sciences program (SPSS), version 23. Among the 650 cases of cUTI, 284 (44%) were males and 366 (56%) were females, with dysuria being the most common symptom (34%). The biggest risk factor for developing cUTI was diabetes (35%). The predominant pathogen was Escherichia coli (53%), followed by Klebsiella spp. (16%), Enterococcus faecalis (7%), Pseudomonas aeruginosa (7%), Candida spp. (2%), and Enterobacter cloacae (2%). Over the years, E. coli emerged as the predominant ESBL and AmpC producer, Acinetobacter baumannii as the multidrug-resistant bug, and Klebsiella pneumoniae as the major carbapenem-resistant Enterobacterales (CRE) producer. Nitrofurantoin emerged as the most effective drug for cystitis. Aminoglycosides, piperacillin-tazobactam, and carbapenems demonstrated the highest activity with an overall resistance of less than 10%. Higher resistance (30%) was observed against cephalosporins, fluoroquinolones, and trimethoprim/sulfamethoxazole. Analysis of the 10-year trend threw up some unexpected results. As expected, resistance increased from 2008 to 2013. Surprisingly, however, antimicrobial resistance in 2018 was lower against majority of the antimicrobials compared to 2013. There is a paucity of data for developing evidence-based guidelines management of cUTI. Targeted antibiograms and not cumulative antibiograms are essential for promoting appropriate prescribing and optimizing patient care. The welcome decline in resistance may be attributed cascade reporting, introduction of more ID physicians. Another possibility is increased utilization of fluoroquinolones which spared the other groups of antimicrobials. Judicious heterogeneous mixing of antimicrobials should be spearheaded in both cystitis and pyelonephritis so that there is no undue pressure on one drug. We strongly recommend carbapenem-sparing protocols in treatment of cUTI when anticipating augmented resistance due to AmpC production. Synergistic combinations such as piperacillin-tazobactam plus aminoglycosides/fluoroquinolones may be prescribed. In sepsis, however, carbapenems are the drugs of choice.

NDM-beta-lactamase-1: Where do we stand?

Multidrug-resistant (MDR) Gram-negative bacilli (GNB) have been playing havoc in the field of nosocomial as well as community-acquired infections. Of particular concern are the carbapenem-resistant GNBs, belonging to Enterobacteriaceae and encoding for New Delhi metallo-beta-lactamase-1 (NDM-1) gene. These strains spread rapidly and horizontally in the population, thus exhibiting MDR traits as these can harbour several resistance encoding genes to almost all antimicrobial groups. Several predisposing factors are responsible towards its spread, viz. excessive antibiotic usage, improper aseptic conditions by healthcare workers, lack of awareness, abruptly discontinuing medication course, alternative medications and vector-borne factors contributing to the unchecked harbouring of these super bugs in India. Thus, a bugle call has already been sounded worldwide especially in India, where the country has taken serious cognizance to build up strategy via implementation of several national programs to combat antimicrobial resistance covering human, animal, agriculture and environmental aspects. As there is an exponential rise in variants of NDM-1 harbouring strains, molecular epidemiological investigations of these strains using genotyping techniques are of paramount importance for a better understanding of this rampant spread and curbing resistance thereafter. This review explores the urgent need to develop a cost-effective, rapid molecular assay, viz. the loop-mediated isothermal amplification method for field detection of MBL harbouring bacterial strains, especially NDM-1 and its variants, thus targeting specific carbapenemase genes at a grass root level even to the remote and rural regions of the country.

DETECTION OF COLISTIN RESISTANCE IN MULTIDRUG-RESISTANT GRAM-NEGATIVE BACILLI: PERFORMANCE OF THE BD PHOENIX AUTOMATED SYSTEM VERSUS THE BROTH MICRODILUTION METHOD

Introduction: The increased dissemination of multidrug-resistant Gram-negative bacilli along with a lag in the development of novel, broad-spectrum antimicrobials determined the reintroduction of colistin into clinical practice. In this context, antibiotic susceptibility testing for colistin using high-performance methods has become a requirement. Objective: We compared the performances of the Becton Dickinson (BD) Phoenix 50 automated system and the Micronaut MIC-Strip, a commercial broth microdilution (BMD) method, for the detection of colistin resistance in clinical multidrug-resistant Gram-negative bacilli, isolated from patients admitted in a tertiary hospital in southern Romania. Methods: 54 clinical isolates with different multidrug-resistant phenotypes (Enterobacterales and Pseudomonas aeruginosa) were tested for colistin susceptibility with the BD Phoenix 50 automated system and the Micronaut MIC-Strip, following the Clinical Laboratory Standard Institute recommendations (CLSI, 2021) and were further classified according to the interpretative categories (resistant and intermediate, respectively). The statistical data was calculated using Microsoft Excel 2007 and OpenEPI software. Results: BD Phoenix system failed to detect 11 colistin resistant isolates (false susceptibility). By contrast, all 38 clinical isolates defined as intermediate by the BMD method were also classified as intermediate by the Phoenix system. Conclusion: BD Phoenix system is a reliable technology for detecting colistin resistance. However, high rates of false susceptibility were observed for the BD Phoenix system, indicating that the intermediate / susceptible results should be confirmed with the standard BMD method. Keywords: colistin susceptibility testing, Gram-negative bacilli, multidrug resistance.