Multidrug-resistant Gram-negative Bacteria Infections Research Articles

Analysis of factors influencing the risk of secondary infection in patients colonized or infected with multidrug-resistant Gram-negative bacteria following hospitalization

We seek to investigate the multifaceted factors influencing secondary infections in patients with multidrug-resistant Gram-negative bacteria (MDR-GNB) colonization or infection post-hospitalization. A total of 100 patients with MDR-GNB colonization or infection were retrospectively reviewed, encompassing those admitted to both the general ward and intensive care unit of our hospital from August 2021 to December 2022. Patients were categorized into the control group (non-nosocomial infection, n = 56) and the observation group (nosocomial infection, n = 44) based on the occurrence of nosocomial infection during hospitalization. Clinical data were compared between the two groups, including the distribution and antibiotic sensitivity of MDR-GNB before nosocomial infection. Significant differences were observed between the two groups in terms of age, underlying diseases, immune status, length of stay, and invasive medical procedures (P < 0.05). The observation group also had fewer patients practicing optimized hygiene, strict isolation, and antibiotic control than the control group (P < 0.05). Factors influencing the risk of secondary infection after hospitalization in patients colonized or infected with MDR-GNB included patient age, underlying diseases, immune status, length of hospitalization, medical invasive procedures, optimized hygiene, strict isolation, and antibiotic control (P < 0.05). The length of hospitalization and treatment cost in the observation group were higher than those in the control group (P < 0.05). This study comprehensively analyzes the intricate mechanisms of secondary infections in patients with MDR-GNB infections post-hospitalization. Key factors influencing infection risk include patient age, underlying diseases, immune status, length of hospitalization, medical invasive procedures, optimized hygiene, strict isolation, and antibiotic control.

Clinical outcomes of intensive care unit patients infected with multidrug-resistant gram-negative bacteria treated with ceftazidime/avibactam and ceftolozane/tazobactam.

In intensive care units (ICUs), infection rates range from 18 to 54%, which is five to ten times higher than those observed in other hospital units, with a mortality rate of 9% to 60%. In recent decades, the susceptibility pattern has changed and Gram-Negative Bacteria (GNB) have become a threat due to their high frequency of multidrug resistance associated with a scarcity of therapeutic options. However, the drugs Ceftolozane/Tazobactam (C/T) and Ceftazidime/Avibactam (C/A) are demonstrating good clinical and microbiological response in the treatment of severe nosocomial infections. Therefore, this study aims to evaluate the clinical outcome of patients with severe infections caused by Multidrug-Resistant (MDR) GNB treated with C/T and C/A. Our study evaluates a total of 131 patients who received treatment with C/T and C/A due to infections caused by MDR GNB within the period from 2018 to 2021. The main infections were urinary tract (46,6%) and respiratory (26,7%) infections. Pseudomonas aeruginosa was the prevailing agent in the sample evaluation (34.3%), followed by Klebsiella pneumoniae (30,1%). About 54,9% of patients showed a favorable response, with culture negativation in 66,4% of the samples, with no discrepancy in negativations when comparing ages: 67,7% in young and 66% in elderly patients. Among the patients, 62,6% received monotherapy with C/T and C/A with a better response observed with monotherapy compared to combination therapy (58,6% vs 41,4%). The overall mortality rate was 45%, with MDR GNB infections responsible for 33,9% of these deaths, and the others (66,1%) due to factors such as oncological, hematological, and degenerative neurological diseases. In regards to hematological aspect, 35,1% of patients showed changes, with 28,2% of them presenting anemia, 4,5% thrombocytopenia, and 2,5% thrombocytosis. Concerning the use of invasive devices, higher mortality was observed in patients on mechanical ventilation (52%). In this manner, it was possible to observe that therapy with C/T and C/A yielded a favorable clinical outcome in patients with severe infections caused by MDR GNB in the study. These drugs also demonstrated good tolerability regardless of age or the presence of preexisting comorbidities and were deemed safe when assessing adverse effects. Our data also demonstrate the importance of determining the mechanism of resistance to carbapenems so that these drugs can be used more effectively and rationally.

Prevalence of and risk factors for intestinal colonisation by multidrug-resistant Gram-negative bacteria in patients with haematological malignancies: A systematic review and meta-analysis

BackgroundPatients with haematological malignancies (HM patients) are at high risk of infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB). MDR-GNB intestinal colonisation is associated with MDR-GNB infections. The aim of this systematic review and meta-analysis on HM patients was to pool the prevalence of and risk factors for intestinal colonisation by MDR-GNB, including carbapenem-resistant Enterobacterales (CRE) and extended-spectrum β-lactamase (ESBL)-producing Enterobacterales, reported in previous studies. MethodsThis study was conducted according to the protocol registered in PROSPERO (CRD42022374425). PubMed, Embase, Web of Science, Ovid MEDLINE(R) ALL and Cochrane Library were searched from inception to 25 October 2022. Observational studies reporting CRE and/or ESBL intestinal colonisation in HM patients were included. Subgroup analyses were conducted by study region. ResultsA total of 21 402 HM patients from 32 studies were analysed. The pooled CRE and ESBL colonisation rates were 21.7% [95% confidence interval (95%CI) 18.7–24.8] and 19.2% (95%CI 13.9–24.5), respectively. Prior exposure to tigecycline [odds ratio (OR) 3.99, 95%CI 2.08–7.68], carbapenem (OR 1.84, 95%CI 1.13-2.97) or penicillin (OR 1.72, 95%CI 1.05–2.83), as well as chemotherapy (OR 2.45, 95%CI 1.05–5.73), neutropenia (OR 1.88, 95%CI 1.08–3.26) and acute myeloid leukaemia (AML; OR 1.86, 95%CI 1.33–2.61), were risk factors for CRE colonisation in HM patients. Prior antibiotic exposure was a risk factor for ESBL colonisation in HM patients (OR 4.90, 95%CI 2.76–8.70). ConclusionsThis study shows the high prevalence of MDR-GNB (CRE and ESBL) colonisation in HM patients and explains associated factors for the colonisation. The results provide evidence for MDR-GNB infection control in HM management.

Analysis of Pathogenic Bacterial Spectrum, Drug Resistance and Risk Factors for Mortality of Bloodstream Infection in Patients with Hematologic Diseases

To analyze the pathogenic bacterial spectrum, drug resistance, and risk factors associated with multidrug-resistant bacterial infection and mortality in patients with hematologic diseases complicated by bloodstream infections, so as to provide reference for rational drug use and improving prognosis. Positive blood culture specimens of patients with hematologic diseases in two Class A tertiary hospitals of Shanxi province from January 2019 to December 2021 were retrospectively analyzed. Pathogen distribution, drug resistance and outcomes of patients with bloodstream infection were investigated, then the multivariate logistic analysis was performed to analyze the risk factors of multidrug-resistant bacterial infection and factors affecting prognosis. 203 strains of pathogens were identified, mainly Gram-negative bacteria (GNB) (69.46%, 141/203), of which Escherichia coli (E.coli) had the highest incidence (41.13%, 58/141), followed by Klebsiella pneumoniae (20.57%, 29/141) and Pseudomonas aeruginosa (12.77%, 18/141). Extended-spectrum beta-lactamase (ESBL)-producing E.coli and Klebsiella pneumoniae were 46.55% (27/58) and 37.93% (11/29), respectively. Carbapenem-resistant Gram-negative bacteria accounted for 10.64% (15/141). And Gram-positive bacteria accounted for 27.59% (56/203), Staphylococcus epidermidis, Streptococcus pneumoniae, and Staphylococcus aureus were the most frequently isolated pathogen among Gram-positive bacteria (14.29%, 12.50% and 10.71%, respectively), of which methicillin-resistant Staphylococcus aureus accounted for 33.33% (2/6), coagulase-negative staphylococci accounted for 87.50% (7/8), without vancomycin- or linezolid-resistant strain. Additionally, fungi accounted for 2.95% (6/203), all of which were Candida. Multidrug-resistant Gram-negative bacteria (MDR-GNB) accounted for 53.90% (76/141). Duration of neutropenia >14 days was a risk factor for developing MDR-GNB infection. The 30-day all-cause mortality was 10.84%. Multivariate logistic regression analysis showed that the significant independent risk factors for mortality were age≥60 years (P <0.01, OR =5.85, 95% CI: 1.80-19.07) and use of vasopressor drugs (P <0.01, OR =5.89, 95% CI: 1.83-18.94). The pathogenic bacteria of bloodstream infection in patients with hematological diseases are widely distributed, and the detection rate of multidrug-resistant bacteria is high. The clinicians should choose suitable antibiotics according to the results of bacterial culture and antibiotic susceptibility test.

Predictors and Outcomes of Multidrug-Resistant Gram-Negative Bacterial Bloodstream Infections in Pediatric Oncology Patients

Background Pediatric patients with cancer are at great risk of infection either from disease process or after being immuno-suppressed by chemotherapy and radiotherapy, this is especially with gram negative and multidrug resistant (MDR) pathogens. The primary aim of our study is to detect the frequency of multidrug resistant gram negative bacteria (MDR-GNB) infections at the Pediatric Oncology Department. The secondary aim is to identify the patterns of resistance of different pathogens to commonly used antimicrobials and detect the risk factors and outcomes of MDR-GNB infections in pediatric oncology patients. Patients and Methods We studied episodes of fever and /or bacteremia in children (aged 1 m to 18 y) with hematologic and solid malignancies in the pediatric oncology department in Ain Shams University Hospital between January 2020 and March 2021. We studied different risks for MDR-GNB including sex, age, underlying malignancy, the presence of indwelling catheter, absolute neutrophil count and other laboratory investigations. Results MDR bacteria were isolated in about 15% samples. The most commonly detected MDR-GNB pathogens were Klebsiella (61.1%) and Acintobacter (22.2%). Among studied patients, MDR-GNB were significantly reported among patients with T-lymphoblastic lymphoma (p = 0.006). Although most patients were neutropenic, neutrophil count was not significantly correlated (p = 0.981). Low serum albumin on the other hand was significantly correlated with MDR-GNB (p = 0.009). Conclusion MDR-GNB is a significant threat to pediatric oncology patients. Contact precautions for all patients with colonization or infection with MDR pathogens and an antimicrobial stewardship based on local epidemiology should be implemented to prevent MDR infections.

Risk Factors for Infection With Multidrug-Resistant Gram-Negative Bacteria in a Tertiary Care Hospital in Saudi Arabia: A Case-Control Study.

Background The increase in the incidence of multidrug-resistant (MDR) organisms especially Gram-negative bacteria (GNB) in healthcare facilities is a serious cause of concern. This study identified risk factors for the infection with these MDR GNB, such asAcinetobacterbaumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli to inform healthcare workers about strategies for their containment. Methods A case-control study was carried out at a tertiary care hospital where 100 patients with healthcare-associated infections (infections arising 48 hours after admission) caused by MDR GNB were compared with two control groups, i.e., 100 patients with healthcare-associated infections caused by non-MDR GNB (not meeting the criteria of MDR) and 100 patients without infection caused by GNB. MDR bacteria were defined as the ones that were non-susceptible to at least one antibiotic in three or more classes of antibiotics. The data were analyzed using descriptive statistics (frequency and percentage of categorical variables). Multivariate regression analysis was undertaken to identify significant predictors of MDR GNB. Odds ratios with 95% confidence intervals were calculated, and the level of significance was determined at p-value < 0.05. Results A total of 388 organisms were isolated during four months (January-April 2015) from 332 patients. Fifty-six (17%) of the patients were infected with more than one organism. Among the MDR bacteria, the most dominant MDR organism wasA. baumannii(38%), followed byK.pneumoniae(31%),P. aeruginosa(20%), andE. coli(11%). Among the non-MDR organisms, the most dominant wasP. aeruginosa(47%), followed byE. coli (32%),K.pneumoniae (18%), andA. baumannii(3%). Patients with MDR organisms compared with the first control group (patients with non-MDR organisms) showed that prior antibiotic use (p-value: 0.001), intensive care unit (ICU) admission (p-value: 0.001), and indwelling medical devices (p-value: 0.005) were significant risk factors for MDR infections. It was also found that the risk factors for MDR GNB infection were the same in the second control group (patients without infection): prior antibiotic use (p-value: 0.002), ICU admission (p-value: 0.001), and indwelling medical devices (p-value: 0.03). Based on the comparison of the two control groups, prolonged hospital stays of more than five days (p-value: 0.001), immunosuppressive therapy (p-value: 0.02), and over 60 years of age (p-value: 0.02) were significant risk factors for non-MDR infection. Conclusion The risk factors identified in our study provide guidance to healthcare workers for the prevention and containment of MDR GNB.

Wide-spectrum antibiotic prophylaxis guarantees optimal outcomes in drowned donor kidney transplantation

ABSTRACT Background Drowned victims possibly obtain various pathogens from drowning sites. Using drowned renal donors to expand the donor pool still lacks consensus due to the potential risk of disease transmission. Research design and methods This retrospective study enrolled 38 drowned donor renal recipients in a large clinical center from August 2012 to February 2021. A 1:2 matched cohort was generated with donor demographics, including age, gender, BMI, and ICU durations. Donor microbiological results, recipient perioperative infections, and early post-transplant and first-year clinical outcomes were analyzed. Results Compared to the control group, drowned donors had significantly increased positive fungal cultures (36.84% vs.13.15%, p = 0.039). Recipients in the drowned group had significantly higher rates of gram-negative bacteria (GNB) and multidrug-resistant GNB infections (23.68% vs.5.26%, 18.42% vs. 3.95%, both p < 0.05). Other colonization and infections were also numerically more frequent in the drowned group. Drowned donor recipients receiving inadequate antibiotic prophylaxis had more perioperative bloodstream infections, higher DGF incidences, and more first-year respiratory tract infections and recipient loss than those receiving adequate prophylaxis (all p < 0.05). Clinical outcomes were similar between the adequate group and the control group. Conclusions Drowned donors could be suitable options under wide-spectrum and adequate antimicrobial prophylaxis.

No more tears from surgical site infections in interventional pain management.

As the field of interventional pain management (IPM) grows, the risk of surgical site infections (SSIs) is increasing. SSI is defined as an infection of the incision or organ/space that occurs within one month after operation or three months after implantation. It is also common to find patients with suspected infection in an outpatient clinic. The most frequent IPM procedures are performed in the spine. Even though primary pyogenic spondylodiscitis via hematogenous spread is the most common type among spinal infections, secondary spinal infections from direct inoculation should be monitored after IPM procedures. Various preventive guidelines for SSI have been published. Cefazolin, followed by vancomycin, is the most commonly used surgical antibiotic prophylaxis in IPM. Diagnosis of SSI is confirmed by purulent discharge, isolation of causative organisms, pain/tenderness, swelling, redness, or heat, or diagnosis by a surgeon or attending physician. Inflammatory markers include traditional (C-reactive protein, erythrocyte sedimentation rate, and white blood cell count) and novel (procalcitonin, serum amyloid A, and presepsin) markers. Empirical antibiotic therapy is defined as the initial administration of antibiotics within at least 24 hours prior to the results of blood culture and antibiotic susceptibility testing. Definitive antibiotic therapy is initiated based on the above culture and testing. Combination antibiotic therapy for multidrug-resistant Gram-negative bacteria infections appears to be superior to monotherapy in mortality with the risk of increasing antibiotic resistance rates. The never-ending war between bacterial resistance and new antibiotics is continuing. This article reviews prevention, diagnosis, and treatment of infection in pain medicine.

Ceftolozane/Tazobactam and Ceftazidime/Avibactam: An Italian Multi-center Retrospective Analysis of Safety and Efficacy in Children With Hematologic Malignancies and Multi-drug Resistant Gram-negative Bacteria Infections.

Ceftolozane/Tazobactam and Ceftazidime/Avibactam: An Italian Multi-center Retrospective Analysis of Safety and Efficacy in Children With Hematologic Malignancies and Multi-drug Resistant Gram-negative Bacteria Infections.

Update of clinical application in ceftazidime-avibactam for multidrug-resistant Gram-negative bacteria infections.

Multidrug-resistant Gram-negative bacteria (MDR-GNB) have become a major global public health threat.Ceftazidime-avibactam (CAZ-AVI) is a newer combination of β-lactam/β-lactamase inhibitor, with activity againstcarbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant Pseudomonas aeruginosa (CRPA). Theaim of this review is to describe the recent real-world experience of CAZ-AVI for the infections due to MDR-GNB. We searched PubMed, Embase and Google Scholar for clinical application in CAZ-AVI forMDR-GNB infections. Reference lists were reviewed and synthesized for narrative review. MDRGNBinfections are associated with higher mortality significantly comparing to drug-susceptible bacterial infections.Fortunately, CAZ-AVI shows significant benefits for infections due to KPC or OXA-48 CRE, comparing to colistin,carbapenem, aminoglycoside and other older agents, even in those with immunocompromised status. The efficacyof CAZ-AVI varies in different infection sites due to CRE, which is lower in pneumonia. Early use is associated withimproved clinical outcomes. Noteworthy, when adopted as salvage therapy, CAZ-AVI is still superior to other GNBactive antibiotics. CAZ-AVI plus aztreonam is recommended as the first line of MBL-CRE infections. However, forinfections caused by KPC- and OXA-48-producing isolates, further investigations are needed to demonstrate thebenefit of combination therapy. Besides CRE, CAZ-AVI is also active to MDR-PA. However, the development ofresistance in CRE and MDR-PA against CAZ-AVI is alarming, and more investigations and studies are needed toprevent, diagnose, and treat infections due to CAZ-AVI-resistant pathogens. CAZ-AVIappears to be a valuable therapeutic option in MDR-GNB infections. Using CAZ-AVI appropriately to improveefficacy and decrease the emergence of resistance is important.

Efficacy and safety of Colistin-Imipenem/Cilastatin combination Therapy for Multidrug-Resistant Gram-Negative Bacteria Infections in Critically Ill Pediatric Patients

Purpose: The aim of this study was to ensure the safety and efficacy of intravenous administration of colistin-imipenem/cilastatin combination to critically ill pediatrics suffering from multidrug-resistant gram-negative sepsis. Patients and methods: The study was designed to give sixty patients in Al-Demerdash hospital pediatric intensive care units (PICU), Ain Shams University, Cairo, Egypt, either imipenem/cilastatin as a monotherapy (thirty patients) or colistin-imipenem/cilastatin intravenously as a combination (thirty patients). The interventional prospective randomized study was performed with focusing on patients' hemodynamic parameters, vital signs, sepsis markers and microbiological response. Results: Thirty patients received intravenous colistin-imipenem/cilastatin combination; with median age of 8.5 months (range: 1-36 months). The isolated bacteria were Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa and Escherichia coli. Klebsiella pneumoniae was the most common isolate (51.7%) of the overall examined sixty patients. Patient who received the combination therapy, was associated with improving in vital signs and hemodynamic parameters with significant p = 0.001, and microbiological responses were represented by the recorded cultures. No patients were defined by renal impairment or neurological toxicity as a side effect to colistin therapy. However, non-significant differences in fatality was found among the two groups with p = 0.108. Conclusion: Colistin combination therapy resulted in better clinical outcomes of PICU patients, which were represented by eradication of the multidrug-resistant gram-negative bacteria without noticeable nephrotoxicity.

Analysis of the clinical application of ceftazidime-avibactam in China

BackgroundThe efficacy and safety of ceftazidime-avibactam were mainly reported in phase II and phase III clinical trials, rarely in the real-world study. The limited real-world study which evaluated the clinical response of this drug shown inconsistent results. This study aimed to investigate the rationality of the clinical use of ceftazidime-avibactam and to evaluate its clinical response in the treatment of multidrug-resistant gram-negative bacteria (MDR-GNB) infections in China. MethodsThis retrospective study evaluated the outcomes of adult patients with MDR-GNB infections treated with ceftazidime-avibactam during September 2018 to August 2020. Patients’ characteristics, comorbidities, microbes, laboratory indicators and medication information were collected. The rationality of ceftazidime-avibactam clinical use, and its clinical response in the treatment of MDR-GNB infections were analyzed. ResultsA total of 30 patients were included in this study, of which, 66.6% received target treatment, 26.7% received empirical treatment, and 6.7% received treatment with no indication. Only 50.0% (11/22) of patients were administrated the recommended dose according to the drug instruction or guidelines, at a median treatment duration of 10 days (range: 2–74 days). The most common source of infection was pneumonia (53.6%, 15/28). Carbapenem-resistant Klebsiella pneumoniae was the predominant pathogen (65%, 13/20). A total of 16 patients (61.5%) achieved clinical response. Patients received target treatment had higher clinical response rate than that of patients received empirical treatment (77.8% vs 25.0%, P = 0.026). A total of 11 patients (61.1%) achieved microbiological response. One patient occurred gastrointestinal adverse reactions. ConclusionsIt is necessary to strengthen the monitor of the clinical application of ceftazidime-avibactam, such as the appropriate indication, reasonable dosage and duration, to improve its clinical outcome. Our results showed that ceftazidime-avibactam might be a potencial choice for the MDR-GNB infections. However, further research are still needed to identify its efficacy and safety in the real world.

Characterisation of mobile colistin resistance genes (mcr-3 and mcr-5) in river and storm water in regions of the Western Cape of South Africa

BackgroundColistin is regarded as a last-resort antimicrobial against multi-drug resistant Gram-negative bacteria (GNB), therefore the dissemination of colistin resistance in the environment is of great concern. Horizontal transfer of mobile colistin resistance (mcr) genes to potential pathogens poses a serious problem. This study aimed to describe the presence of colistin resistant GNB and mcr genes in river and storm water in regions of the Western Cape.MethodsWater samples were collected from three rivers during May 2019 and January 2020 and two storm water samples were collected in November 2019. Colistin resistant GNB were cultured on MacConkey agar containing colistin and identified by MALDI-TOF. Colistin resistance was confirmed using broth microdilution (BMD). mcr-1-5 genes were detected by PCR performed directly on the water samples and on the colistin resistant isolates. mcr functionality was assessed by BMD after cloning the mcr genes into pET-48b(+) and expression in SHuffle T7 E. coli.Resultsmcr-5.1 and various mcr-3 gene variants were detected in the Plankenburg-, Eerste- and Berg rivers and in storm water from Muizenberg, and only mcr-5.1 was detected in storm water from Fish Hoek. Colistin resistant GNB were isolated from all of the water sources. Aeromonas spp. were the most common colistin resistant organisms detected in the water sources; 25% (6/24) of colistin resistant Aeromonas spp. isolated from the Berg river contained novel mcr-3 variants; mcr-3.33 (n = 1), mcr-3.34 (n = 1) mcr-3.35 (n = 1) mcr-3.36 (n = 2) and mcr-3.37 (n = 1), which were confirmed to confer colistin resistance.ConclusionsThe mcr-5.1 and mcr-3 colistin resistance gene variants were present in widely dispersed water sources in regions of the Western Cape. The mcr genes were only detected in water sampled downstream of and alongside communities, suggesting that their presence is driven by human influence/contamination. This is the first documentation of mcr-3 and mcr-5 gene variants in any setting in South Africa. Spill-over of these genes to communities could result in horizontal gene transfer to pathogenic bacteria, exacerbating the challenge of controlling multidrug resistant GNB infections.

Phage Digestion of a Bacterial Capsule Imparts Resistance to Two Antibiotic Agents.

Bacteriophages are viruses that infect bacteria, replicating and multiplying using host resources. For specific infections, bacteriophages have developed extraordinary proteins for recognizing and degrading their host. Inspired by the remarkable development of viral proteins, we used the tail fiber protein to treat multiple drug-resistant Acinetobacter baumannii. The tail fiber protein exhibits polysaccharide depolymerases activity which specifically degrades exopolysaccharide (EPS) during the phage–host interaction. However, EPS-degraded cells are observed altering host susceptibility to bacterial lysis peptide, the endolysin-derived peptide. Notably, endolysin is necessary in the process of progeny liberation by breaking the bacterial cell wall. Surprisingly, peeling the EPS animated host to resist colistin, the last-resort antibiotic used in multidrug-resistant Gram-negative bacteria infection. Tail fiber-modified cell wall reduces colistin attachment, causing temporary antibiotic-resistance and possibly raising clinical risks in treating multiple drug-resistant A. baumannii.

Molecular Characterization of Carbapenem Resistant Klebsiella pneumoniae in Malaysia Hospital.

The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) is a great concern, as carbapenems are the last-line therapy for multidrug-resistant Gram-negative bacteria infections. This study aims to report the epidemiology of CRKP in a teaching hospital in Malaysia based on the molecular genotypic and clinical characteristics of the isolates. Sixty-three CRKP strains were isolated from a tertiary teaching hospital from January 2016 until August 2017. Carbapenemase genes were detected in 55 isolates, with blaOXA-48 (63.5%) as the predominant carbapenemase gene, followed by blaNDM (36.5%). At least one porin loss was detected in nine isolates. Overall, 63 isolates were divided into 30 clusters at similarity of 80% with PFGE analysis. Statistical analysis showed that in-hospital mortality was significantly associated with the usage of central venous catheter, infection or colonization by CRKP, particularly NDM-producers. In comparison, survival analysis using Cox proportional hazards regression identified a higher hazard ratio for patients with a stoma and patients treated with imipenem but a lower hazard ratio for patients with NDM-producing CRKP. OXA-48 carbapenemase gene was the predominant carbapenemase gene in this study. As CRKP infection could lead to a high rate of in-hospital mortality, early detection of the isolates was important to reduce their dissemination.

Clinical characteristics and risk factors for the isolation of multi-drug-resistant Gram-negative bacteria from critically ill patients with COVID-19

BackgroundWe investigated the clinical characteristics and risk factors for the isolation of multi-drug-resistant (MDR) Gram-negative bacteria (GNB) from critically ill COVID-19 patients.MethodsWe retrospectively matched (1:2) critical COVID-19 patients with one or more MDR GNB from any clinical specimen (cases), with those with no MDR GNB isolates (controls).ResultsSeventy-eight cases were identified (4.5 per 1000 intensive care unit (ICU) days, 95% confidence interval (CI) 3.6–5.7). Of 98 MDR GNB isolates, the most frequent species were Stenotrophomonas maltophilia (24, 24.5%), and Klebsiella pneumoniae (23, 23.5%). Two (8.7%) K. pneumoniae, and six (85.7%) Pseudomonas aeruginosa isolates were carbapenem resistant. A total of 24 (24.5%) isolates were not considered to be associated with active infection. Those with active infection received appropriate antimicrobial agents within a median of one day. The case group had significantly longer median central venous line days, mechanical ventilation days, and hospital length of stay (P<0.001 for each). All-cause mortality at 28 days was not significantly different between the two groups (P=0.19). Mechanical ventilation days (adjusted odds ratio 1.062, 95% CI 1.012–1.114; P=0.015), but not receipt of corticosteroids or tocilizumab, was independently associated with the isolation of MDR GNB. There was no association between MDR GNB and 28-day all-cause mortality (adjusted odds ratio 2.426, 95% CI 0.833–7.069; P= 0.104).ConclusionIn critically ill COVID-19 patients, prevention of MDR GNB colonization and infections requires minimizing the use of invasive devices, and to remove them as soon as their presence is no longer necessary.

Evaluating Cefiderocol in the Treatment of Multidrug-Resistant Gram-Negative Bacilli: A Review of the Emerging Data.

Infections due to multidrug-resistant Gram-negative bacteria (MDR-GNB), especially when carbapenem resistant, have been very difficult to manage in the last fifteen years, owing to the paucity of dependable therapeutic options. Cefiderocol is a siderophore cephalosporin recently approved by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) that may have the potential to fill some of the remaining gaps in the treatment of MDR-GNB infections. Among others, cefiderocol demonstrated in vitro activity against carbapenem-resistant Acinetobacter baumannii and metallo-β-lactamases producers. Clinical data from both registrative studies and post-marketing experiences are essential to confirm whether these promises from in vitro studies could readily translate into clinical practice, as well as to delineate the precise place in therapy for cefiderocol for the treatment of MDR-GNB in the near future. Because of its unique potential, it is essential to provide both randomized controlled trials (RCT) and real-life data to improve the ability of clinicians to exploit its benefit in both empirical and targeted treatment of MDR-GNB infections. In this narrative review, we discuss the emerging data from pivotal RCT and initial real-life experiences on the use of cefiderocol for the treatment of MDR-GNB infections.

Clinical characteristics and outcomes of patients with multidrug-resistant Gram-negative bacterial infections treated with ceftazidime/avibactam

ObjectivesThe aim of this study was to investigate the clinical characteristics and outcomes of patients with infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB) treated with ceftazidime/avibactam (CAZ/AVI) during the period September 2019 to June 2020 since CAZ/AVI had been marketed in China. MethodsA total of 20 MDR-GNB-infected patients were retrospectively identified using the electronic medical record system in West China Hospital. ResultsThe mean age of the 20 patients was 54.5 ± 17.37 years and 14 (70%) were male. Pneumonia (n = 12; 60%), complicated intra-abdominal infection (n = 10; 50%), and bloodstream infection (n = 7; 35%) were the most common infection sources. Klebsiella pneumoniae (55% 18/33) was the predominant pathogen. The 14-day clinical cure rate was 45%. The 14-day and 30-day mortality rates were 25% and 55%, respectively. No significant difference was found in 30-day mortality between treatment with CAZ/AVI monotherapy and combination regimens (P > 0.05). Three patients suffered from adverse drug reactions such as diarrhoea. ConclusionNo significant difference was found between the effectiveness of CAZ/AVI in the clinical failure and cure groups as salvage treatment of MDR-GNB infection.

Dissecting the Molecular Mechanism of Colistin Resistance in mcr-1 Bacteria.

Colistin or polymyxin B is the last resort antibiotic to treat infections of multidrug-resistant Gram-negative bacteria by disrupting their outer membranes. The recent emergence of Gram-negative bacteria that demonstrate colistin resistance, particularly plasmid-mediated mobile colistin resistance (mcr), poses a big challenge to the treatment of multidrug resistance infections. Using molecular dynamics simulations, we explore the mechanism of colistin resistance in a model lipid A bilayer mimicking the Gram-negative mcr-1 bacterial outer membrane. The simulation results reveal that the outer membrane of normal Gram-negative bacteria is stabilized by salt bridges between positively charged divalent ions and negatively charged phosphate groups of the membranes. In the presence of positively charged polymyxin B, these salt bridges are disrupted, and calcium is released into the aqueous phase, resulting in membrane disruption. In contrast, the lipid A in the outer membrane of mcr-1 bacteria has a novel modification, this being a covalently attached phosphoethanolamine group. This group enables the formation of a large number of hydrogen bonds between the amine and phosphate groups, resulting in an electrostatic net on the membrane. This extensive noncovalent electrostatic cross-linking between the lipid molecules collectively enhances the membrane stability and results in resistance to the action of cationic peptides such as polymyxin B. The simulation results shed new atomistic insights for understanding the mechanistic basis of colistin resistance and provide clues for the design of new membrane disruptors and permeabilizers to treat mcr-1 infections.

Ceftolozane/Tazobactam and Ceftazidime/Avibactam for Multidrug-Resistant Gram-Negative Infections in Immunocompetent Patients: A Single-Center Retrospective Study.

Complicated infections from multidrug-resistant Gram-negative bacteria (MDR-GNB) represent a serious problem presenting many challenges. Resistance to many classes of antibiotics reduces the probability of an adequate empirical treatment, with unfavorable consequences, increasing morbidity and mortality. Readily available patient medical history and updated information about the local microbiological epidemiology remain critical for defining the baseline risk of MDR-GNB infections and guiding empirical treatment choices, with the aim of avoiding both undertreatment and overtreatment. There are few literature data that report real-life experiences in the use of ceftolozane/tazobactam and ceftazidime/avibactam, with particular reference to microbiological cure. Some studies reported experiences for the treatment of MDR-GNB infections in patients with hematological malignancies or specifically in Pseudomonas aeruginosa infections. We report our clinical single-center experience regarding the real-life use of ceftolozane/tazobactam and ceftazidime/avibactam to treat serious and complicated infections due to MDR-GNB and carbapenem-resistant Enterobacterales (CRE), with particular regard given to intra-abdominal and urinary tract infections and sepsis.