Carbapenem-resistant Gram-negative Bacteria Research Articles

Phenotypic characterization of carbapenem non-susceptible gram-negative bacilli isolated from clinical specimens.

BackgroundMultidrug resistant, extremely drug-resistant, pan-drug resistant, carbapenem-resistant, and carbapenemase-producing gram-negative bacteria are becoming more common in health care settings and are posing a growing threat to public health.ObjectiveThe study was aimed to detect and phenotypically characterize carbapenem no- susceptible gram-negative bacilli at the Ethiopian Public Health Institute.Materials and methodsA prospective cross-sectional study was conducted from June 30, 2019, to May 30, 2020, at the national reference laboratory of the Ethiopian Public Health Institute. Clinical samples were collected, inoculated, and incubated for each sample in accordance with standard protocol. Antimicrobial susceptibility testing was conducted using Kirby-Bauer disk diffusion method. Identification was done using the traditional biochemical method. Multidrug-resistant and extensively drug-resistant isolates were classified using a standardized definition established by the European Centre for Disease Prevention and Control and the United States Centers for Disease Prevention and Control. Gram-negative organisms with reduced susceptibility to carbapenem antibiotics were considered candidate carbapenemase producers and subjected to modified carbapenem inactivation and simplified carbapenem inactivation methods. Meropenem with EDTA was used to differentiate metallo-β-lactamase (MBL) from serine carbapenemase. Meropenem (MRP)/meropenem + phenylboronic acid (MBO) were used to differentiate Klebsiella pneumoniae carbapenemase (KPC) from other serine carbapenemase producing gram-negative organisms.ResultsA total of 1,337 clinical specimens were analyzed, of which 429 gram-negative bacterial isolates were recovered. Out of 429 isolates, 319, 74, and 36 were Enterobacterales, Acinetobacter species, and Pseudomonas aeruginosa respectively. In our study, the prevalence of multidrug-resistant, extensively drug-resistant, carbapenemase-producing, and carbapenem nonsusceptible gram-negative bacilli were 45.2%, 7.7%, 5.4%, and 15.4% respectively. Out of 429 isolates, 66 demonstrated reduced susceptibility to the antibiotics meropenem and imipenem. These isolates were tested for carbapenemase production of which 34.8% (23/66) were carbapenemase producers. Out of 23 carbapenemase positive gram-negative bacteria, ten (10) and thirteen (13) were metallo-beta-lactamase and serine carbapenemase respectively. Three of 13 serine carbapenemase positive organisms were Klebsiella pneumoniae carbapenemase.ConclusionThis study revealed an alarming level of antimicrobial resistance (AMR), with a high prevalence of multidrug-resistant (MDR) and extremely drug-resistant, carbapenemase-producing gram-negative bacteria, particularly among intensive care unit patients at the health facility level. These findings point to a scenario in which clinical management of infected patients becomes increasingly difficult and necessitates the use of “last-resort” antimicrobials likely exacerbating the magnitude of the global AMR crisis. This mandates robust AMR monitoring and an infection prevention and control program.

The role of Gram-negative bacteria in skin and soft tissue infections.

Skin and soft tissue infections (SSTIs) are a leading cause of morbidity, emergency department visits and hospitalization. In recent years, the spread of carbapenem-resistant gram-negative bacteria (GNB) is also increasing in SSTIs. However, the armamentarium of available drugs is recently expanding as well. In this review, we reported the most recent data and about management and treatment of SSTIs caused by GNB, mainly for the treatment of carbapenem-resistant Enterobacterales (CRE), Pseudomonas spp and Acinetobacter spp. The increasing incidence of carbapenem-resistant GNB is challenging for management and treatment, considering the high rate of inappropriate empiric and targeted antimicrobial treatments. The role of new antibiotics, mainly licensed for the treatment of other infections, is an object of continuous debate. As a matter of fact, no specific clinical trials on SSTIs have been performed for new drugs; however, recent data about the use in real life of new compounds in clinical practice are available. Some recently approved drugs are actually considered the backbone of targeted therapy in patients with severe infections caused by susceptible carbapenem-resistant GNB strains. Prompt diagnosis of cSSTIs is crucial and, when necessary, surgical debridement for source control of infection is the milestone of the treatment. The physicians should be confident to identify patients at high risk for multidrug-resistant pathogens to minimize inappropriate empiric therapy.

Molecular Surveillance of Carbapenem-Resistant Gram-Negative Bacteria in Liver Transplant Candidates.

Background: Carbapenem-resistant Gram-negative bacteria (CRGN) cause life-threatening infections due to limited antimicrobial treatment options. The occurrence of CRGN is often linked to hospitalization and antimicrobial treatment but remains incompletely understood. CRGN are common in patients with severe illness (e.g., liver transplantation patients). Using whole-genome sequencing (WGS), we aimed to elucidate the evolution of CRGN in this vulnerable cohort and to reconstruct potential transmission routes.Methods: From 351 patients evaluated for liver transplantation, 18 CRGN isolates (from 17 patients) were analyzed. Using WGS and bioinformatic analysis, genotypes and phylogenetic relationships were explored. Potential epidemiological links were assessed by analysis of patient charts.Results: Carbapenem-resistant (CR) Klebsiella pneumoniae (n=9) and CR Pseudomonas aeruginosa (n=7) were the predominating pathogens. In silico analysis revealed that 14/18 CRGN did not harbor carbapenemase-coding genes, whereas in 4/18 CRGN, carbapenemases (VIM-1, VIM-2, OXA-232, and OXA-72) were detected. Among all isolates, there was no evidence of plasmid transfer-mediated carbapenem resistance. A close phylogenetic relatedness was found for three K. pneumoniae isolates. Although no epidemiological context was comprehensible for the CRGN isolates, evidence was found that the isolates resulted of a transmission of a carbapenem-susceptible ancestor before individual radiation into CRGN.Conclusion: The integrative epidemiological study reveals a high diversity of CRGN in liver cirrhosis patients. Mutation of carbapenem-susceptible ancestors appears to be the dominant way of CR acquisition rather than in-hospital transmission of CRGN or carbapenemase-encoding genetic elements. This study underlines the need to avoid transmission of carbapenem-susceptible ancestors in vulnerable patient cohorts.

Clinical management of cUTI, cIAI, and HABP/VABP attributable to carbapenem-resistant Gram-negative infections in Spain.

IntroductionCarbapenem-resistant Gram-negative (CRGN) infections are a major public health problem in Spain, often implicated in complicated, healthcare-associated infections that require the use of potentially toxic antibacterial agents of last resort. The objective of this study was to assess the clinical management of complicated infections caused by CRGN bacteria in Spanish hospitals.MethodsThe study included: 1) a survey assessing the GN infection and antibacterial susceptibility profile in five participating Spanish hospitals and 2) a non-interventional, retrospective single cohort chart review of 100 patients with complicated urinary tract infection (cUTI), complicated intra-abdominal infection (cIAI), or hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia (HABP/ VABP) attributable to CRGN pathogens.ResultsIn the participating hospitals CRGN prevalence was 9.3% amongst complicated infections. In the retrospective cohort, 92% of infections were healthcare-associated, and Klebsiella pneumoniae and Pseudomonas aeruginosa were the most common pathogens. OXA was the most frequently detected carbapenemase type (71.4%). We found that carbapenems were frequently used to treat cUTI, cIAI, HABP/VABP caused by CRGN pathogens. Carbapenem use, particularly in combination with other agents, persisted after confirmation of carbapenem resistance. Clinical cure was 66.0%, mortality during hospitalization 35.0%, mortality at the time of chart review 62.0%, and 6-months-post-discharge readmission 47.7%.ConclusionOur results reflect the high burden and unmet needs associated with the management of complicated infections attributable to CRGN pathogens in Spain and highlight the urgent need for enhanced clinical management of these difficult-to-treat infections.

Acceptance and outcome of interventions in a meropenem de-escalation antimicrobial stewardship program in pediatrics.

Prospective audit and feedback is a method that allows the antimicrobial stewardship program (ASP) team to interact with attending physicians to tailor antibiotic therapy, including de-escalation, as appropriate. This study aimed to evaluate the acceptance and outcomes of ASP de-escalation recommendations in children who received meropenem. A prospective cohort study was conducted in children aged 1 month to 18 years who received meropenem in a tertiary-care teaching hospital. The ASP team gave recommendation between 72 and 120 h after initiating meropenem therapy. Acceptance of de-escalation recommendations among primary physicians was evaluated within 24 h of recommendation. Outcomes included clinical success rate on the 7th day and incidence rate of acquisition of carbapenem-resistant gram-negative bacteria (CR-GNB) within 30 days. From March to December 2019, 217 children with a median (interquartile range) age of 2.1 (0.6, 9.5) years received meropenem. The ASP team gave recommendations in 127 (58.5%) of cases for continuation of meropenem therapy and 90 (41.5%) of cases for de-escalation. The overall acceptance of ASP de-escalation recommendations was 57.8% (95%CI: 46.9-68.1%). Clinical success rates were 85.2% in the accepted group compared to 77.5% in the rejected group (P = 0.06). The incidence rate of acquisition of CR-GNB within 30 days after treatment was 5.8% in the accepted group and 15.8% in the rejected group (P = 0.03). About half of the recommendations to de-escalate meropenem prescriptions were accepted through the ASP intervention. Carbapenem-resistant gram-negative bacteria acquisitions was less likely in the de-escalation group. A robust de-escalation strategy 72 h following carbapenem initiation should be encouraged to combat multidrug-resistant organisms.

Trend analysis of carbapenem-resistant Gram-negative bacteria and antimicrobial consumption in the post-COVID-19 era: an extra challenge for healthcare institutions

The incidence density trend of the carbapenem-resistant Gram-negative bacteria was analysed in device-associated infections and antimicrobial consumption in 99 critical care facilities in a low/middle-income country, between January 2019 and December 2020. Carbapenem-resistant Acinetobacter baumannii (CRAB) per 1000 patient-days increased in 2020 and this finding had a strong positive correlation with the incidence density of COVID-19 by the Spearman test. Polymyxin consumption also increased in 2020 but without significant correlation with CRAB or COVID-19 incidence density, presumably due to empirical and untargeted prescribing as a consequence of concern about CRAB infections. These findings are a warning to infection control programmes and antimicrobial stewardship.

Cost-Effectiveness of Molecular Method Diagnostic for Rapid Detection of Antibiotic-Resistant Bacteria

ObjectivesThis study aimed to perform a cost-effectiveness analysis (CEA) of the molecular diagnostic method (MM) associated with conventional diagnostic method (CM) compared with the CM alone, for the detection of resistant profile in bacteremia, from the perspective of the Brazilian Public Health System, in intensive care units setting. MethodsThe clinical parameters regarding methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Gram-negative bacteria (CRGNB), and vancomycin-resistant Enterococcus spp. (VRE) infections were collected from searches on PubMed, Scopus, and SciELO, using specific keywords. Data on direct medical costs to treat these infections were collected according to Brazilian Public Health System perspective from Brazilian databases, in tables of 2018 to 2019. CEA was performed after building a dynamic model, which was calibrated and validated according to international recommendations. The incremental cost-effectiveness ratio of the MM + CM compared with the CM was calculated using the outcomes “avoided death” and “avoided resistant infections.” One-way sensitivity analyses were performed. ResultsThis CEA demonstrated that the MM + CM was dominant in all scenarios. Estimates showed that for MRSA, CRGNB, and VRE infections, every avoided death would lead to savings of Brazilian real (R$) 4.9 million ($937 301), R$2.2 million ($419 899), and R$1.3 million ($248 919), respectively. The same infections assessed by avoided resistant infections savings were projected to be R$24 964 ($4686), R$40 260 ($7558), and R$23 867 ($4480). ConclusionsMM leads to cost reduction and increased benefits, optimizing the use of financial resources on the health system in the intensive care unit setting, in bacteremia caused by MRSA, CRGNB, and VRE.

Pharmacist-led quality control circle in sustained reduction of carbapenem-resistance at a Chinese tertiary teaching hospital.

The spread of carbapenem-resistant Gram-negative bacteria poses a substantial threat to morbidity and mortality worldwide, which is mainly attributed to the overuse of carbapenem. This study aimed to evaluate the use of a quality control circle (QCC) in controlling the overuse of carbapenems and improving the state of carbapenem resistance at a Chinese tertiary teaching hospital. A pharmacist-led multidisciplinary QCC project was carried out and the plan-do-check-act (PDCA) method was applied for 12 months. The data on carbapenem consumption, bacterial identification, and antibacterial susceptibility testing were collected to evaluate the effect of this project. The antibiotics use density (AUD) of carbapenems exhibited a decreasing trend over time (P<0.001), and the AUD of meropenem, imipenem, and biapenem decreased by 30.20%, 42.45%, and 78.05% after the intervention, respectively. The total AUD of carbapenems decreased from 7.37 to 3.96, which included the decrease in the irrational use of carbapenems by 1.61, accounting for 47.21% of the total. Moreover, the positive correlations were discovered between the resistance rate of carbapenem-resistant Klebsiella pneumonia (CRKP)/Acinetobacter baumannii (CRAB) and the AUD of carbapenems (P<0.05). The resistance rate of CRKP and CRAB decreased from 51.93% and 89.21% to 32.94% and 60.66%, respectively, following QCC project implementation. This is the first study to highlight the success of a multifaceted intervention QCC project and PDCA method, which led to a significant reduction in the AUD and resistance rate of carbapenems. QCC is a feasible and effective management tool for improving the quality of carbapenem use in medical institutions.

Efficacy Assessment of High Dose Colistin against Carbapenem-Resistant Gram-Negative Bacteria (CR-GNB) in Critically Ill Patients: A Retrospective Non-Inferiority Trial

Background: Colistin is an effective treatment option, recommended for carbapenem resistant gram-negative bacilli (CR-GNB) in critically ill patients. Due to high nephrotoxicity, dose management of Colistin is a tough decision to make. At standard dosage the efficacy of Colistin is not well defined. Consequently, strategies involving higher dosages were suggested. Objective: To evaluate the high dose of Colistin as non-inferior to standard dose in the treatment of CR-GNB in critically ill patients. Study Design: Retrospective comparative study Place and Duration of Study: Intensive Care Unit, King Saud Medical City Riyadh, Saudi Arabia from 1st January 2015 to 31st December 2017. Methodology: One hundred and ninety two patients that met the inclusion criteria from all participants were further divided into two groups. Group H (High dose) given the high dose of Colistin (9 million units intravenously (IV) loading dose, and then 9 million units/day in 2 or three divided doses) whereas group S was administered with standard dose (no loading dose, 6 million units/day). The primary endpoint of the study was the assessment of nephrotoxicity after the start of Colistin and secondary endpoints were the mortality within 14 days of commencing Colistin along with clinical effects and microbial clearance upon completion of treatment. Results: The results of the study established the non-inferiority of high dose of Colistin for the renal safety and also showed significant improvement in microbial clearance and length of ICU stay as compared to the standard dose. The other secondary end points such as mortality (p = 0.99), length of hospital stay (p = 0.39), and global improvement (p value of 0.06) revealed no significant difference between the two groups. Conclusion: The high dose of Colistin for the treatment of carbapenem resistance gram negative bacilli (CRGNB) was as safe as the standard dose for renal safety. But we also found that it also accelerates microbial clearance and reduces the time spent in the intensive care unit. Key words: Colistin, Colestimethate sodium, Gram negative bacteraemia, Sepsis, Multi-drug resistant organisms, Acute kidney injury

Risk factors for bloodstream infection by multidrug-resistant organisms in critically ill patients in a reference trauma hospital

Bloodstream infections (BSI) by multidrug-resistant (MDR) organisms are responsible for significant mortality in critically ill trauma patients. Our objective is to identify the risk factors for BSI by MDR agents and their resistance mechanisms in a trauma reference hospital. During 18 months, all patients admitted in our Intensive Care Unit (ICU) were enrolled in this prospective cohort. We included the first episode of BSI by carbapenem-resistant Gram-negative bacteria, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin resistant enterococcus. Demographic and clinical data were compared among patients with and without BSI and variables with P < .05 were tested in a multivariate analysis. We performed PCR for identification of carbapenemase and SCC mec genes and Pulsed-field gel electrophoresis for clonality. Out of 1,528 patients, 302 (19.8%) were trauma and 66 (4.3%) had a MDR-BSI (19.5% were trauma). The multivariate analysis showed that mechanical ventilation (OR3.16; 95% CI 1-8; P=.02), hemodialysis (OR3.16; 95% CI 1-5; P=.0003) and surgery (OR1.76; 95% CI 1-3; P=.04) were independent risk factors for MDR-BSI. The most frequent MDR were Klebsiella pneumoniae (n=26) and MRSA (n=27). Regarding K pneumoniae strains (n=24), 20 (83.8%) harbored bla KPC gene and 1 bla NDM. The majority of KPC isolates belonged to a predominant clone; while the MRSA were polyclonal and SCC mec type II. Mechanical ventilation, surgery and hemodialysis were independent risk factors for MDR-BSI in our cohort, but trauma was not. KPC was the main mechanism of resistance among carbapenem-resistant K pneumoniae that belonged to a predominant clone which could indicate cross-transmission.

Does cefiderocol heteroresistance explain the discrepancy between the APEKS-NP and CREDIBLE-CR clinical trial results?

Does cefiderocol heteroresistance explain the discrepancy between the APEKS-NP and CREDIBLE-CR clinical trial results?

Clinical Efficacy of Ceftazidime-Avibactam in the Treatment of Infections Caused by Carbapenem–Resistant Gram-Negative Bacteria

The wide spread of carbapenemases among gram-negative bacteria of the Enterobacterales order in hospitals around the world, including Russia, creates great difficulties in the effective use of antibiotics for these infections in the ICU. Ceftazidime-avibactam is the first antibiotic developed and studied for the treatment of infections caused by carbapenem-resistant enterobacteria. Ceftazidime-avibactam shows high activity against producers of class A and D serine carbapenemases (KPC and OXA-48). In combination with aztreonam it is effective in infections caused by producers of class B metallo-beta-lactamases (NDM and VIM). The review analyzes the results of 19 non-comparative and 10 comparative studies of ceftazidime-avibactam in infections caused by carbapenem-resistant Enterobacterales, as well as case reports. According to the data of non- comparative studies, the clinical efficacy of ceftazidime-avibactam ranged from 45.0 to 87.2%, on average 71.7±11.3%, and the eradication rate of KPC or OXA-48 carbapenemase producers ranged from 40.0 to 100%, on average 65.5±18.6%. The effectiveness of ceftazidime-avibactam in comparative studies was 67.9±17.3%, which was significantly higher compared to other antibiotics (44.3±14.4%,P=0.012). Treatment with ceftazidime-avibactam was accompanied by a significantly lower 30-day mortality in contrast to other antibiotics – 23.8±13.5% and 41.0±13.6%, respectively,P=0.001. The development of resistance in Enterobacterales species to ceftazidime-avibactam during therapy is rarely observed, on average 5.4±4.4%, which characterizes a rather low potential of the antibiotic in resistance selection. Early administration of ceftazidime-avibactam is accompanied by better treatment results as opposed to delayed therapy. Treatment of infections caused by carbapenem-resistant enterobacteria with ceftazidime-avibactam is associated with a significantly higher recovery rate and a lower mortality compared to other regimens of antibacterial therapy.

Phenotypic Methods for the Detection of Metallo-Beta-Lactamase Production by Gram-negative Bacterial Isolates from Hospitalized Patients in A Tertiary Care Hospital in India

Drug-resistant bacteria are a global health concern owing to the high morbidity and mortality they can cause, especially in countries such as India. Gram-negative bacteria, including Enterobacteriaceae, Pseudomonas, and Acinetobacter, are primarily responsible for expanding the scope of drug resistance. These antibiotic-resistant pathogens are particularly associated with serious infections in hospitals. The production of carbapenemase by gram-negative bacteria appears to be the major reason for their resistance to carbapenems. The study was a prospective study done from March 2018 to December 2020. All the carbapenem-resistant isolates from various clinical samples were further tested for the production of carbapenemases/metallo-beta-lactamases production by various phenotypic tests like carbaNp, Imipenem–EDTA combined disc synergy test, Double-disc synergy test and E-test methods. Of all carbapenem-resistant gram-negative bacteria isolated from patients in a hospital in India, 237 (88.1%) carbapenemase producers were identified, among which 217 (91.5%) were metallo-beta-lactamase (MBL) producers. Therefore, the detection of MBL producers is important for preventing their infectious spread. The present study revealed that most MBL producers were isolated from patients of 0–9 to years of age (63.9%). The double-disc synergy test (DDST) and E-test MBL strips were more sensitive than the combined disc test in detecting MBLs. Because the DDST was the simplest and most effective method, it can be used for the routine laboratory screening of MBL producers in hospitals.

Formation &lt;i&gt;in vitro&lt;/i&gt; of colistin resistance in carbapenem-resistant Gram-negative bacteria and its biological cost

Introduction. The spread of resistance to carbapenems among gram-negative bacteria have led to an increase in the consumption of polymyxins and the emergence of certain strains resistant to them. Polymyxin resistance is mainly associated with mutations in chromosomal genes. The development of mutational resistance to antibiotics can lead to a decrease in the viability of bacteria; which is manifested by an increase in the duration of the cell cycle; a decrease in virulence and competitive fitness.The purpose of the study was to assess in vitro the intensity of the formation of colistin resistance in carbapenemresistant clinical isolates of gram-negative bacteria; the stability of the formed emerged resistance and its biological cost.Materials and methods. For 46 strains of Klebsiella pneumoniae; 77 strains of Pseudomonas aeruginosa and 42 strains of Acinetobacter baumannii; real time polymerase chain reaction (PCR) was used to detect the genes of carbapenemases; the minimum inhibitory concentrations (MIC) of meropenem and colistin were determined by broth microdilution method. The selection of resistant subpopulations on Muller–Hinton agar with the addition of 16 mg/l colistin was carried out. For colistin-resistant mutants and their isogenic sensitive strains; the kinetic parameters of growth in broth culture were determined. Incubation and result recording were performed on an Infinite M200 microplate reader for 18.5 hours at 35°C with measurement of light scatter in the wells every 15 minutes.Results. The production of carbapenemases MBL VIM in P. aeruginosa; MBL NDM; KPC and OXA-48 in K. pneumoniae; OXA-23 and OXA-40 in A. baumannii was observed. All strains were sensitive to colistin (MIC varied from 0.062 to 2 mg/l). The colony growth on a selective medium with16 mg/l colistin was observed for 97.8% of K. pneumoniae strains; 16.9% of P. aeruginosa strains; and 61.9% of A. baumannii strains. The mutational nature of colistin resistance was confirmed for 21.7% of K. pneumoniae strains. For colistin-resistant mutants of K. pneumoniae; a significant increase in the duration of the lag phase (Tlag) was observed: 225.6 ± 7.037 min in the wild-type susceptible strains and 245.5 ± 8.726 in resistant mutants; p = 0.037. The indicators of the doubling time of the number of microbial cells in the exponential growth phase (Tdoubling) and the area under the bacterial growth curve did not differ significantly.Conclusion. A high frequency of formation of colistin resistance in vitro in carbapenemase-producing strains of K. pneumoniae was observed. The absence of significant changes in the kinetics of microbial growth in resistant strains makes it possible to predict the further spread of mutational resistance to colistin; as well as its preservation in microbial populations of K. pneumoniae even in the case of limiting the use of this antibiotic.

Efficacies of Colistin-Carbapenem versus Colistin-Tigecycline in Critically Ill Patients with CR-GNB-Associated Pneumonia: A Multicenter Observational Study.

Background: Evaluating the options for antibiotic treatment for carbapenem-resistant Gram-negative bacteria (CR-GNB)-associated pneumonia remains crucial. We compared the therapeutic efficacy and nephrotoxicity of two combination therapies, namely, colistin + carbapenem (CC) versus colistin + tigecycline (CT), for treating CR-GNB-related nosocomial pneumonia in critically ill patients. Methods: In this multicenter, retrospective, and cohort study, we recruited patients admitted to intensive care units and diagnosed with CR-GNB-associated nosocomial pneumonia. We divided the enrolled patients into CC (n = 62) and CT (n = 59) groups. After propensity score matching (n = 39), we compared the therapeutic efficacy by mortality, favorable outcome, and microbiological eradication and compared nephrotoxicity by acute kidney injury between groups. Results: There was no significant difference between the CC and CT groups regarding demographic characteristics and disease severities as assessed using the Acute Physiology and Chronic Health Evaluation (APACHE) II score, Sequential Organ Failure Assessment (SOFA) score, and other organ dysfunction variables. Therapeutic efficacy was non-significantly different between groups in all-cause mortality, favorable outcomes, and microbiological eradication at days 7, 14, and 28; as was the Kaplan-Meier analysis of 28-day survival. For nephrotoxicity, both groups had similar risks of developing acute kidney injury, evaluated using the Kidney Disease Improving Global Outcomes criteria (p = 1.000). Conclusions: Combination therapy with CC or CT had similar therapeutic efficacy and risk of developing acute kidney injury for treating CR-GNB-associated nosocomial pneumonia in critically ill patients.

Risk Factors for Neutropenic Sepsis Related Mortality in Children Undergoing Allogenic Hematopoietic Stem Cell Transplantation.

We aimed to analyze infections in children undergoing hematopoietic stem cell transplantation (HSCT) until engraftment. The spectrum and risk factors associated will help plan interventions to reduce mortality. We performed a retrospective analysis on the infections, associated risk factors, and mortality until engraftment in children up to 18years of age undergoing HSCT from January 2017 to August 2020. A total of 399 children were included, with a male: female ratio of 1.9:1, with matched related donor HSCT in 36.6%, a matched unrelated donor in 18.3%, and haploidentical HSCT in 38.1% of children. Culture positive bacteremia was documented in 22.1% transplants with gram-negative bacteria (GNB) isolated in 71/88 (80%). Among the GNB, the predominant organism was Klebsiella pneumonia in 38 (53%), E.coli in 16 (22%), Pseudomonas in 9 (12%). Carbapenem resistance was documented in 24/71 (33%). The incidence of possible, probable, and proven fungal infections in the cohort was 63 (15%), 28 (7%), and 6 (1.5%), respectively. Mortality up to engraftment due to sepsis in our cohort is 3.3% (n = 13). There was a significant association between mortality and a perianal focus (30.8%, p value 0.029) and the presence of carbapenem resistance (38%, p value 0.002). Mortality among those who developed proven fungal infections was significantly higher than those with bacteremia (p value 0.004). Our study has identified fungal sepsis and carbapenem-resistant GNB sepsis as high-risk groups for mortality. Risk directed interventions in these groups would help ensure survival and optimal outcomes.

Complicated carbapenem-resistant infections: a treatment pathway analysis in Italian sites.

Efforts to curb a growing prevalence of carbapenem resistance are prominent worldwide and especially in countries where high levels of carbapenem resistance are reported, such as Italy. Complicated infections, including complicated urinary tract infections (cUTI), complicated intra-abdominal infections (cIAI), and hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP), are often caused by carbapenem-resistant Gram-negative (CRGN) bacteria and as such, these infection sites and their causative bacteria are important areas of focus for healthcare practitioners seeking to follow good antimicrobial stewardship practices. The aim of this study was to assess the clinical management and associated clinical and economic outcomes of patients with cUTI, cIAI, and HABP/VABP resulting from CRGN bacteria in Italy. We first conducted a hospital survey focusing on Gram-negative infections and their antibacterial susceptibility profile in four participating Italian hospitals. The second part of the study involved a non-interventional, retrospective single cohort chart review of 100 patients with cUTI, cIAI, or HABP/VABP caused by CRGN bacteria, in which patient characteristics, index hospitalization characteristics, infection characteristics, patient outcomes, treatment pathways, and healthcare resource use were assessed. The hospital survey demonstrated carbapenem resistance in approximately 17% of complicated infections, mostly associated with Acinetobacter baumannii. The non-interventional, retrospective cohort component showed that complicated CRGN infections were hospital- or healthcare-acquired in 99.0% of cases and were most often caused by Klebsiella pneumoniae (66.0%). Despite the carbapenem-resistant nature of the included infections, carbapenems were used in 19.0% of patients as empirical therapy, in 43.0% as late empirical (i.e. immediately before receipt of susceptibility test results), and in 64.0% as targeted therapy (post-susceptibility test result receipt). Colistin was used in 61.0% of patients after susceptibility results were available. High clinical and economic burden was evident, with the average length of hospital stay being greater than 50 days, clinical cure achievement in only 43.0% of patients, and an overall mortality rate of 65.0% by the end of the follow-up period. Our results reflect the considerable burden associated with complicated CRGN infections in Italy and the limitations in current treatment strategies. Our study pinpoints potential areas for improvement. For example, regular and detailed local surveillance and state of the art microbial diagnostic capabilities might aid and hasten clinical decision-making and facilitate improved antimicrobial stewardship when treating complex CRGN infections. New therapeutic options which more appropriately address CRGN infections may assist in improving outcomes which are important to both patients and healthcare providers.

Determination of carbapenemase genes in clinical isolates using Cepheid Xpert Carba-R

Detection of carbapenem resistance genes is a critical issue for hospitals due to possible recommendations for infection control and targeted therapy. The Cepheid Xpert instrument, a Carba-R test for the detection and differentiation of five common carbapenemase genes, was tested from September 2020 to February 2021. As part of the approbation, 20 tests were provided. This review presents the results of the approbation of a relatively regular sensitivity study on Siemens WalkAway‑96 plus. Cepheid Xpert Carba-R analysis has been shown to be an accurate and fast tool for detecting colonization by carbapenem-resistant gram-negative bacteria, which can help limit the spread of these organisms in hospitals.

Clinical Features of Post-Operative Nosocomial Meningitis in Adults and Evaluation of Efficiency of Intrathecal Treatment.

Background: Post-operative nosocomial meningitis is a critical complication that develops in patients after neurosurgical interventions and operations. Patients and Methods: Data were collected for 65 patients who were diagnosed as having nosocomial meningitis after neurosurgery. The agent profile, clinical and biochemical differences in gram-negative and gram-positive meningitis, and the effectiveness of intrathecal antibiotic administration in cases with carbapenem-resistant gram-negative agents were evaluated. Results: Gram-negative bacteria were isolated in 52.3% of patients. In gram-negative cases of post-operative nosocomial meningitis, white blood cell count (p = 0.015), C-reactive protein (p = 0.001), cerebrospinal fluid leukocyte count (p = 0.0001), and protein (p = 0.0001) were higher, and glucose (p = 0.002) was lower. Concurrent bacteremia (p = 0.041), 14-day mortality (p = 0.022), and 30-day mortality (p = 0.023) were higher in gram-negative cases. Empirical treatment was appropriate in 78.5% of the patients. Seventeen patients (26.2%) received intrathecal antibiotic agents in addition to intravenous antibiotic treatment because of carbapenem-resistant gram-negative bacteria. Nine (53%) of the patients receiving intrathecal therapy had Acinetobacter baumannii as the agent, six had Klebsiella pneumoniae (35.4%), one had Pseudomonas aeruginosa (5.8%), and one had Providencia rettgeri (5.8%). The mean intravenous treatment duration was 21.4 ± 10.6 (4-60) days, and the mean intrathecal treatment duration was 17.6 ± 14.0 (1-51) days. Eleven patients received colistimethate sodium intrathecally (1 × 10 mg/d), three patients received amikacin intrathecally (1 × 10 mg/d), and three patients received gentamicin intrathecally (1 × 10 mg/d). Clinical and microbiologic treatment success was achieved in nine patients (53%). Conclusions: In cases of meningitis caused by carbapenem-resistant agents, intrathecal administration of antibiotic agents such as gentamicin, amikacin, and colistin with limited blood-brain barrier transition in intravenous administration will increase survival. Therefore, intrathecal antibiotic administration should be considered as a part of routine of nosocomial meningitis.

New antibiotics for the treatment of nonfermenting Gram-negative bacteria.

To discuss the current literature on novel agents for the treatment of carbapenem-resistant nonfermenting Gram-negative bacteria (NF-GNB) infections. Some novel agents have recently become available that are expected to replace classical polymyxins as the first-line options for the treatment of carbapenem-resistant NF-GNB infections. In this narrative review, we provide a brief overview of the differential activity of various recently approved agents against NF-GNB most encountered in the daily clinical practice, as well as the results from phase-3 randomized clinical trials and large postapproval observational studies, with special focus on NF-GNB. Since resistance to novel agents has already been reported, the use of novel agents needs to be optimized, based on their differential activity (not only in terms of targeted bacteria, but also of resistance determinants), the local microbiological epidemiology, and the most updated pharmacokinetic/pharmacodynamic data. Large real-life experiences remain of crucial importance for further refining the optimal treatment of NF-GNB infections in the daily clinical practice.