Gram-negative Bacilli Infections Research Articles

Change in Klebsiella pneumoniae susceptibility profile after the arrival of ceftazidime-avibactam in an Argentinean intensive care unit: a new ecological landscape.

Ceftazidime-avibactam (CZA) is a good option for Gram-negative bacilli infections that produce carbapenemase Classes A (especially blaKPC) and D (blaOXA). However, it is unknown whether it would have an impact on metallo-β-lactamases (blaMBL) selection. The aim of the study was to compare carbapenem and CZA Klebsiella pneumoniae (KPN) susceptibility profiles for a period of two years following the introduction of CZA. The study was conducted in a 36-bed adult ICU of a tertiary hospital in Buenos Aires, Argentina. Antimicrobial consumption was expressed as days of treatment per 100 patients-day (DOT). A total of 123 KPN strains in the first year and 172 in the second year were analyzed. An alarming decrease in carbapenem susceptibility was detected in the second year (OR 0.5 [0.3-0.8] p<.001). In parallel, there was a decrease in CZA susceptibility (OR 0.5 [0.3-0.9] p<.05). These findings were linked to a rise in blaMBL-KPN (32.1% vs. 45.1%, OR 1.7 [1.1-2.9], p <.04) during the second year. This new KPN susceptibility profile promoted an increment in CZA (1.0 DOT vs. 6.6 DOT, OR 6.6 [4.9-9.1] p<.001) and aztreonam (0.3 DOT vs. 4.1 DOT, OR 16.3 [9.1-29.3] p<.001) consumption. Thus, there was a decrease in carbapenem prescription (17.8 DOT vs. 15.4 DOT, OR 0.8 [0.8-0.9] p<.001). There was an escalation of blaMBL-KPN rate two years after CZA introduction, leading to a decrease in CZA and carbapenem susceptibility and an increase in CZA and aztreonam prescriptions.

Clinical outcomes and risk factors for mortality in recipients with carbapenem-resistant gram-negative bacilli infections after kidney transplantation treated with ceftazidime-avibactam: a retrospective study.

Ceftazidime-avibactam is a treatment option for carbapenem-resistant gram-negative bacilli (CR-GNB) infections. However, the risk factors associated with ceftazidime-avibactam (CAZ-AVI) treatment failure in kidney transplant (KT) recipients and the need for CAZ-AVI-based combination therapy remain unclear. From June 2019 to December 2023, a retrospective observational study of KT recipients with CR-GNB infection treated with CAZ-AVI was conducted, with the primary outcome being 30-day mortality and secondary outcomes being clinical cure, microbiological cure, and safety. Risk factors for 30-day mortality and clinical failure were also investigated. A total of 81 KT recipients treated with CAZ-AVI were included in this study. Forty recipients (49.4%) received CAZ-AVI monotherapy, with a 30-day mortality of 22.2%. The clinical cure and microbiological cure rates of CAZ/AVI therapy were 72.8% and 66.7%, respectively. CAZ-AVI alone or in combination with other medications had no effect on clinical cure or 30-day mortality. Multivariate logistic regression analysis revealed that a higher Acute Physiology and Chronic Health Evaluation (APACHE) II score (odds ratio [OR]: 4.517; 95% confidence interval [CI]: 1.397-14.607; P = 0.012) was an independent risk factor for 30-day mortality. Clinical cure was positively associated with the administration of CAZ-AVI within 48 hours of infection onset (OR: 11.009; 95% CI: 1.344-90.197; P=0.025) and negatively associated with higher APACHE II scores (OR: 0.700; 95% CI: 0.555-0.882; P=0.002). Four (4.9%) recipients experienced recurrence within 90 days after the initial infection, 3 (3.7%) recipients experienced CAZ-AVI-related adverse events, and no CAZ-AVI resistance was identified. CAZ-AVI is an effective medication for treating CR-GNB infections following kidney transplantation, even as monotherapy. Optimization of CAZ/AVI therapy (used within 48 hours of infection onset) is positively associated with potential clinical benefit. Further larger-scale studies are needed to validate these findings.

Impact of Gram-Negative Bacilli Resistance Rates on Risk of Death in Septic Shock and Pneumonia.

Sepsis is a major cause of morbidity and mortality worldwide. When selecting empiric antibiotics for sepsis, clinicians are encouraged to use local resistance rates, but their impact on individual outcomes is unknown. Improved methods to predict outcomes are needed to optimize treatment selection and improve antibiotic stewardship. We expanded on a previously developed theoretical model to estimate the excess risk of death in gram-negative bacilli (GNB) sepsis due to discordant antibiotics using 3 factors: the prevalence of GNB in sepsis, the rate of antibiotic resistance in GNB, and the mortality difference between discordant and concordant antibiotic treatments. We focused on ceftriaxone, cefepime, and meropenem as the anti-GNB treatment backbone in sepsis, pneumonia, and urinary tract infections. We analyzed both publicly available data and data from a large urban hospital. Publicly available data were weighted toward culture-positive cases. Excess risk of death with discordant antibiotics was highest in septic shock and pneumonia. In septic shock, excess risk of death was 4.53% (95% confidence interval [CI], 4.04%-5.01%), 0.6% (95% CI, .55%-.66%), and 0.19% (95% CI, .16%-.21%) when considering resistance to ceftriaxone, cefepime, and meropenem, respectively. Results were similar in pneumonia. Local data, which included culture-negative cases, showed an excess risk of death in septic shock of 0.75% (95% CI, .57%-.93%) for treatment with discordant antibiotics in ceftriaxone-resistant infections and 0.18% (95% CI, .16%-.21%) for cefepime-resistant infections. Estimating the excess risk of death for specific sepsis phenotypes in the context of local resistance rates, rather than relying on population resistance data, may be more informative in deciding empiric antibiotics in GNB infections.

Incidence of catheter-associated urinary tract infections by Gram-negative bacilli and their ESBL and carbapenemase production in specialized hospitals of Bahir Dar, northwest Ethiopia

BackgroundCatheter-associated urinary tract infections (CAUTIs) due to multidrug-resistant Gram-negative bacilli (GNB) is a common concern globally. Investigating the incidence of CAUTI and associated antibiotic resistance has paramount importance from the health care associated infections perspective. This study therefore assessed the incidence of CAUTIs due to GNB and the production of extended-spectrum beta-lactamase (ESBL) and carbapenemase among inpatients in specialized hospitals of Northwest, Ethiopia.MethodsA total of 363 patients with indwelling urinary catheters who were admitted in the hospital for > 48 h were consecutively enrolled and followed from 3 to 18 days. Data were collected through interviewing and review of medical records. Patients who developed at least one of the following: fever (> 38 OC), suprapubic tenderness, or costovertebral angle pain, coupled with a GNB positive urine culture of ≥ 103 CFU/mL with no more than two bacterial species were defined as CAUTI. The ESBL and carbapenemase production were detected and identified by chromogenic medium. Logistic regression analysis was done to identify associated factors.ResultsFrom 363 patients followed, the incidence rate of CAUTI was 27.8 per 1000 catheter days. Catheterization for ≥ 8 days (AOR = 10.6, 95%CI:1.8–62.1) and hospitalization for > 10 days (AOR = 8.1, 95%CI: 2.4–27.2) were the factors significantly associated with CAUTIs. E. coli (n = 18, 34.6%), Proteus species (n = 7, 13.5%), and P. aeruginosa (n = 6, 11.5%) were the most frequent GNB. Isolates revealed high rates of resistance to amoxicillin-clavulanic acid (100%), cefazolin (n = 51, 98%), ceftazidime (n = 47, 90%) and cefotaxime (n = 46, 88%). Most of the GNB isolates (86.5%) were multidrug-resistant. Overall, 19.2% and 5.8% of GNB isolates were ESBL and carbapenemase producers, respectively.ConclusionsIncidence of CAUTI with Gram-negative bacilli is high. As most of the GNB isolates are MDR and showed a super high rate of resistance to amoxicillin-clavulanic and third-generation cephalosporins, empirical treatment with these substances is virtually ineffective in patients with suspected GNB infection in Ethiopia. The expression of ESBL and carbapenemase among GNB isolates is also a concern. Therefore, improved infection prevention and control measures, careful use of catheters and third generation of cephalosporins are needed to improve patient outcomes and reduce the burden of CAUTIs and the spreading of antimicrobial resistance.

Comparative study of colistin Methanesulfonate and colistin Sulfate/polymyxin B in the treatment of ceftazidime-avibactam resistant Gram-negative bacilli infections

ObjectiveTo evaluate the clinical efficacy of different species of polymyxin drugs in the treatment of Carbapenem-Resistant Gram-negative bacilli (CR-GNB) resistant to ceftazidime-avibactam (CZA). MethodsPatients infected by CR-GNB strains and treated with polymyxin drugs were selected and divided into colistin methanesulfonate (CMS) group and colistin sulfate/polymyxin B (CSPB) group to observe clinical efficacy and safety. Results65 patients were eventually included (CMS group, n ​= ​29; CSPB group, n ​= ​36). The clinical efficacy, microbiological eradication rate and 28-day mortality between the two groups were similar, with no statistical significance (51.72 ​% vs. 50.00 ​%, p ​= ​0.890; 55.17 ​% vs. 52.78 ​%, p ​= ​0.847; 17.24 ​% vs. 25.00 ​%, p ​= ​0.449). With regard to renal safety, the incidence of acute kidney injury (AKI) in the CMS group was significantly higher than that in the CSPB group (34.48 ​% vs. 5.56 ​%, p ​= ​0.003). Among them, the incidence of AKI grade 3 in the CMS group tended to be higher than that in the CSPB group (24.14 ​% vs. 5.56 ​%, p ​= ​0.066). ConclusionThe results based on small sample size from a single center showed that clinical response to the treatment of ceftazidime-avibactam resistant Gram-negative bacillus infections is similar for CMS and Colistin Sulfate/Polymyxin B, but the nephrotoxicity of CMS is greater than that of polymyxin sulfates.

The Etiology, Antibiotic Therapy and Outcomes of Bacteremic Skin and Soft-Tissue Infections in Onco-Hematological Patients.

to assess the current epidemiology, antibiotic therapy and outcomes of onco- hematological patients with bacteremic skin and soft-tissue infections (SSTIs), and to identify the risk factors for Gram-negative bacilli (GNB) infection and for early and overall mortality. episodes of bacteremic SSTIs occurring in cancer patients at two hospitals were prospectively recorded and retrospectively analyzed. Of 164 episodes of bacteremic SSTIs, 53% occurred in patients with solid tumors and 47% with hematological malignancies. GNB represented 45.5% of all episodes, led by Pseudomonas aeruginosa (37.8%). Multidrug resistance rate was 16%. Inadequate empirical antibiotic therapy (IEAT) occurred in 17.7% of episodes, rising to 34.6% in those due to resistant bacteria. Independent risk factors for GNB infection were corticosteroid therapy and skin necrosis. Early and overall case-fatality rates were 12% and 21%, respectively. Risk factors for early mortality were older age, septic shock, and IEAT, and for overall mortality were older age, septic shock and resistant bacteria. GNB bacteremic SSTI was common, particularly if corticosteroid therapy or skin necrosis. IEAT was frequent in resistant bacteria infections. Mortality occurred mainly in older patients with septic shock, resistant bacteria and IEAT. These results might guide empirical antibiotic therapy in this high-risk population.

Contemporary profile of infective endocarditis in young patients in the era of ageing population: a comparative study

Abstract Aim The aim of the study is to describe the main differences in epidemiological characteristics, clinical features and prognosis between IE patients aged &amp;lt;50 and ≥50 years. Methods A total of 1935 episodes of IE were prospectively recruited at three tertiary centres from 1996 to 2022. Patients were classified into two groups: &amp;lt;50 years (n=333, median age 40 [IQR 33-45] and ≥50 years (n=1602, median age 71 [IQR 64-78]). Variables related to epidemiology, microbiology, echocardiography and outcomes among both groups were analysed. Results The proportion of male patients was higher in those &amp;lt;50 years (73.9% vs 64%; p&amp;lt;0.001). Patients aged ≥50 years had more comorbidities. Time to diagnosis was longer in this group of patients (6.2 ± 1.5 vs 21.7 ± 14.12 days; p&amp;lt;0.001). Proportion of community-acquired IE was higher in &amp;lt;50-year episodes (64.4% vs 81%; p&amp;lt;0.001). Intravenous drug use (IVU) was significantly more frequent in younger patients (22.6% vs 0.5%; p&amp;lt;0.001). Likewise, tricuspid native valve IE was more common in patients &amp;lt;50 years old (16.6% vs 4%; p&amp;lt;0.001). Congenital heart disease (17.2% vs 2.7%; p&amp;lt;0.001) and mitral valve prolapse (6.3% vs 3.8%; p=0.041) were more frequent in patients aged&amp;lt;50 years. Conversely, prosthetic valve IE (38.4% vs 20.7%; p&amp;lt;0.001) was more common in patients &amp;gt;50 years. Streptococcus bovis (0.9% vs 5.6%; p&amp;lt;0.001), enterococci (3% vs 12.6%; p=0.000), coagulase-negative staphylococci (9.9% vs 18.4%; p&amp;lt;0.001) and gram-negative bacilli (1.2% vs 3.5%; p=0.028) infections were more frequent in ≥50-year adults, while the incidence of Streptococcus viridans (21.9% vs 10.7%; p&amp;lt;0.001) and HACEK (1.2% vs 0.3%; p=0.03) infections was higher in the &amp;lt;50-year group. Staphylococcus aureus IE was similar between the two groups (23.7% vs 19.4%; p=0.074). The presence of vegetations (87.4% vs 80.9%; p=0.005), as well as severe new valve regurgitation (42% vs 30.8%; p&amp;lt;0.001) were more often found in &amp;lt;50-year patients. Acute heart failure (44.1% vs 59.5%; p&amp;lt;0.001), acute kidney failure (27.3% vs 47.5%; p&amp;lt;0.001) and septic shock (15.3% vs 20.9%; p=0.02) were more frequent in &amp;gt;50-year group. No differences in frequency of cardiac surgery among both groups were found (61.9% vs 57.6%; p=0.147). In-hospital mortality was significantly higher in ≥50-year patients (15.6% vs 29.2%; p&amp;lt;0.001). Mortality remained higher in ≥50-year adults who underwent cardiac surgery (12.4% vs 23.3%; p=0.001) as well as those who did not undergo surgery (20.5% vs 37.2%; p&amp;lt;0.001). Conclusions Patients aged &amp;lt;50 years diagnosed with IE were more frequently male, and had a higher proportion of community-acquired infections. Congenital heart disease, mitral valve prolapse and IVU were more frequent in &amp;lt;50-year adults. Streptococcus viridans infections were more frequent in this group of patients. In-hospital complications and mortality were lower compared to older patients, regardless of whether they underwent cardiac surgery.

Ceftazidime/avibactam combined with colistin: a novel attempt to treat carbapenem-resistant Gram-negative bacilli infection

BackgroundThe rapid global emergence and spread of carbapenem-resistant Gram-negative bacilli (CR-GNB) is recognized as a major public health concern, and there are currently few effective treatments for CR-GNB infection. The aim of this study was to investigate the clinical characteristics and outcomes of patients with CR-GNB infections treated with ceftazidime/avibactam (CAZ/AVI) combined with colistin from October 2019 to February 2023 in China.MethodsA total of 31 patients with CR-GNB infections were retrospectively identified using the electronic medical record system of Zhejiang Provincial People's Hospital.ResultsThirty-one patients were treated with CAZ/AVI combined with colistin. Respiratory tract infections (87%) were most common. The common drug-resistant bacteria encompass Klebsiella pneumonia (54.8%), Acinetobacter baumannii (29.0%), and Pseudomonas aeruginosa (16.1%). The 30-day mortality rate was 29.0%, and the 7-day microbial clearance rate was 64.5%. The inflammatory marker CRP changes, but not PCT and WBC, were statistically significant on days 7 and 14 after combination therapy. There were seven patients developing acute renal injury (AKI) after combination therapy and treating with continuous renal replacement therapy (CRRT). Two patients developed diarrhea.ConclusionThe combination of CAZ/AVI and colistin has potential efficacy in patients with CR-GNB infection, but more studies are needed to determine whether it can reduce 30-day mortality rates and increase 7-day microbial clearance. At the same time, the adverse reactions of combination therapy should not be ignored.

Antibiotic therapy for nonfermenting Gram-negative bacilli infections: future perspectives.

Serious infections caused by nonfermenting Gram-negative bacteria (NF-GNB) pose a significant challenge for clinicians due to the limited treatment options available, which are frequently associated with issues of toxicity and unfavourable pharmacokinetic profiles. The aim of this review is to provide a brief overview of the existing data concerning the ongoing development of antiinfective agents targeting NF-GNB. Several agents exhibiting efficacy against NF-GNB are under clinical investigation. Durlobactam-sulbactam and cefepime-taniborbactam emerge as promising therapeutic avenues against carbapenem-resistant Acinetobacter baumanii. Cefepime-zidebactam may serve as a suitable treatment option for urinary tract infections caused by a wide range of NF-GNB. Cefepime-enmetazobactam demonstrates potent in vitro activity against various NF-GNB strains; however, its role as an anti-Pseudomonal agent is inadequately substantiated by available data. Xeruborbactam is a wide β-lactamase inhibitor that can be associated with a range of agents, enhancing in-vitro activity of these against many NF-GNB, including those resistant to newer, broader spectrum options. Lastly, murepavadin appears to be a potential pathogen-specific solution for severe Pseudomonas infections; however, additional investigation is necessary to establish the safety profile of this compound. Each of the novel molecules reviewed possesses an interesting range of in-vitro activity against NF-GNB. In addition, some of them have already been proved effective in vivo, underscoring their potential as future treatment options.

Secondary pulmonary infection and co-infection in elderly COVID-19 patients during the pandemics in a tertiary general hospital in Beijing, China.

Most people are infected with COVID-19 during pandemics at the end of 2022. Older patients were more vulnerable. However, the incidence of secondary bacterial, fungal or viral pulmonary infection and co-infection is not well described in elderly hospitalized COVID-19 patients. We retrospectively reviewed the medical records of all elderly (≥65 years) hospitalized patients with laboratory-confirmed COVID-19 from December 1, 2022 to January 31, 2023. Demographics, underlying diseases, treatments, and laboratory data were collected. Univariate and multivariate logistic regression models were used to explore the risk factors associated with secondary bacterial, fungal or viral pulmonary infection and co-infection. A total of 322 older patients with COVID-19 were enrolled. The incidence of secondary bacterial, fungal or viral pulmonary infection and co-infection was 27.3% (88/322) and 7.5% (24/322), respectively. The overall in-hospital mortality of all patients was 32.9% (106/322), and the in-hospital mortality among patients who acquired with secondary pulmonary infection and co-infection was 57.0% (57/100). A total of 23.9% (77/322) of patients were admitted to ICU within 48 h of hospitalization. The incidence of secondary pulmonary infection and co-infection among patients admitted to the ICU was 50.6% (39/77) and 13.0% (10/77), respectively. The overall in-hospital mortality of ICU patients was 48.1% (37/77), and the in-hospital mortality of ICU patients acquired with secondary pulmonary infection and co-infection was 61.4% (27/44). A total of 83.5% (269/322) of the included patients received empirical antibiotic therapy before positive Clinical Microbiology results. Influenza A virus (the vast majority were the H3N2 subtype) was the most common community acquired pathogen for co-infection. While A. baumannii, K. pneumoniae, and P. aeruginosa were the common hospital acquired pathogens for co-infection and secondary pulmonary infection. The incidence of Carbapenem-resistant Gram-negative bacilli (CR-GNB) infections was high, and the mortality reached 76.9%. Predictors of secondary pulmonary infection and co-infection were ICU admission within 48 h of hospitalization, cerebrovascular diseases, critical COVID-19, and PCT > 0.5 ng/mL. The prognosis for elderly hospitalized COVID-19 patients with secondary pulmonary infection or co-infection is poor. The inflammatory biomarker PCT > 0.5 ng/mL played an important role in the early prediction of secondary pulmonary infection and co-infection in COVID-19 patients.

Clinical efficacy and drug resistance of ceftazidime-avibactam in the treatment of Carbapenem-resistant gram-negative bacilli infection.

To examine the clinical efficacy, safety, and resistance of Ceftazidime-Avibactam (CAZ-AVI) in patients with Carbapenem-resistant Gram-negative bacilli (CR-GNB) infections. We retrospectively analyzed relevant data of CR-GNB infected patients receiving CAZ-AVI treatment, analyzed relevant factors affecting drug efficacy, and compared the efficacy and safety with patients receiving Polymyxin B treatment. A total of 139 patients were included. Agranulocytosis, septic shock, SOFA score, and CAZ-AVI treatment course were independent risk factors affecting the prognosis of patients with CR-GNB infection treated with CAZ-AVI while prolonging the treatment course of CAZ-AVI was the only protective factor for bacterial clearance. The fundamental indicators showed no statistically significant differences between CAZ-AVI and Polymyxin B treatment groups. At the same time, the proportion of patients treated with monotherapy was significantly higher in the CAZ-AVI group than in the Polymyxin B group (37.2% vs. 8.9%, p < 0.05), the 30-day mortality rate of the CAZ-AVI treatment group (27.7% vs. 46.7%, p = 0.027) was lower than that of the Polymyxin B treatment group. The 30-day clinical cure rate (59.6% vs. 40% p = 0.030) and 14-day microbiological clearance rate (42.6% vs. 24.4%, p = 0.038) were significantly higher in the CAZ-AVI than in the Polymyxin B treatment group. Eighty nine patients were monitored for CAZ-AVI resistance, and the total resistance rate was 14.6% (13/89). The resistance rates of Carbapenem-resistant Klebsiella pneumoniae (CRKP) and Carbapenem-resistant Pseudomonas aeruginosa (CRPA) to CAZ-AVI were 13.5 and 15.4%, respectively. CAZ-AVI has shown high clinical efficacy and bacterial clearance in treating CR-GNB infections. Compared with Polymyxin B, CAZ-AVI significantly improved the outcome of mechanical ventilation in patients with septic shock, agranulocytosis, Intensive Care Unit (ICU) patients, bloodstream infection, and patients with SOFA score > 6, and had a lower incidence of adverse events. We monitored the emergence of CAZ-AVI resistance and should strengthen the monitoring of drug susceptibility in clinical practice and the rational selection of antibiotic regimens to delay the onset of resistance.

Treatment and prognostic risk factors for intracranial infection after craniocerebral surgery.

The objective of this study was to determine risk factors of pejorative evolution course in patients suffering from postoperative cranial infection. The data of patients who developed an intracranial infection after craniocerebral surgery in the neurosurgical intensive care unit of the First Affiliated Hospital of Nanjing Medical University in Nanjing, Jiangsu, China, from February 2018 to August 2019 were retrospectively analyzed. Logistic regression was used to analyze the factors influencing the prognosis of intracranial infection treatment. Sixty-four patients developed an infection after craniocerebral surgery, and 48 of them with negative CSF cultures received experimental anti-infectives. In 16 patients, cerebrospinal fluid culture showed pandrug-resistant pathogens, including 11 Acinetobacter baumannii (11), Klebsiella pneumoniae (3), Escherichia coli (1), and Candida glabrata (1). Nine patients received intraventricular or intrathecal injections of polymyxin B. The mean duration of infection treatment was 22.2 ± 9.9 days, and the clinical cure rate was 85.9% (55/64). Logistic multivariate regression analysis showed that inadequate CSF drainage (OR, 6.839; 95% CI, 1.130-41.383; P = 0.036) and infection with drug-resistant bacteria (OR, 24.241; 95% CI, 2.032-289.150; P = 0.012) were independent risk factors for postoperative intracranial infection. Intracranial infection with positive CSF culture and inadequate CSF drainage are factors contributing to the poor prognosis of intracranial infection. Moreover, early anti-infection treatment and adequate CSF drainage may improve patient outcomes. In particular, intraventricular or intrathecal injection of polymyxin B may be a safe and effective treatment strategy for MDR/XDR gram-negative bacilli infection.

Prevalence and pattern of multidrug resistant Gram-negative bacilli isolated from patients in the intensive care unit of a tertiary care hospital in Coastal Karnataka

Infections due to Gram negative bacilli (GNB) are the leading cause of mortality in ICU patients and are associated with higher morbidity rates, longer hospital stays and increased healthcare expenditures. Infections due to GNB in the ICU is about 2 to 5 times higher than in the general in-patient hospital population. This study aims to look at the prevalence of multi drug resistant gram-negative bacilli and proportion of ESBL producers in the MICU and to determine susceptibility patterns of GNB isolated, to various antibiotics. A total of 616 samples were collected from 396 patients admitted to the MICU during the 4-month study period. After the samples were inoculated and identified, the gram-negative isolates were subjected to Antibiotic susceptibility testing using Kirby Bauer Disc Diffusion technique with 17 different antibiotic disks. Strains showing decreased sensitivity to Ceftazidime/Cefotaxime were screened for ESBL production. Among the 616 samples tested, 149 (24.2%) samples showed growth of Gram-negative bacteria exclusively. Total number of GNB’s isolated were 173 due to some samples showing polymicrobial growth. The most common GNB found was (27.7%) which was followed by Klebsiella pneumonia at 26.0% and Acinetobacter baumannii at 18.5%. 64.2% of all GNB’s were Multi Drug Resistant which included 75% , 71.1% Klebsiella pneumoniae and 84.4% Acinetobacter baumannii. The study shows that the MDR GNB infections are on the rise in the ICU with GNBs being highly resistant to many previously effective first line antibiotics like Penicillins, newer Cephalosporins and Fluoroquinolones with susceptibility rates below 25% and even 0% for earlier generation Cephalosporins.

Addition of aminoglycosides reduces recurrence of infections with multidrug-resistant Gram-negative bacilli in patients with sepsis and septic shock

Aminoglycosides and beta-lactams have been a recommended regimen in the treatment of sepsis and septic shock despite lack of mortality benefit. Previous studies have examined emergence of resistance for the same bacterial isolate using old dosing regimens and during a narrow follow up window. We hypothesized that combination regimens employing aminoglycosides will decrease the cumulative incidence of infections due to multidrug resistant (MDR) Gram-negative bacilli (GNB) compared to beta-lactams alone. All adult patients admitted to Barnes Jewish Hospital in St. Louis, MO between 2010 and 2017 with the diagnosis of sepsis or septic shock were included in this retrospective cohort study. Patients were divided into 2 treatment groups: with and without aminoglycosides. We extracted patients' demographics, severity of presentation, administered antibiotics, follow up cultures with susceptibility results for a period of 4-60 days, and mortality. After propensity score matching, a Fine-Gray sub-distribution proportional hazards model summarized the estimated incidence of subsequent infections with MDR GNB in the presence of all-cause death as a competing risk. 10212 septic patients were included with 1996 (19.5%) treated with at least 2 antimicrobials including one aminoglycoside. After propensity score matching, the cumulative incidence of MDR GNB infections between 4-60 days was lower in the combination group with an incidence of 0.073 at 60 days (95% CI [0.062, 0.085]) vs 0.116 (95% CI [0.102, 0.130]) in patients not receiving aminoglycosides. Patients younger than 65 years and with hematologic malignancies had a larger treatment effect in subgroup analyses. Addition of aminoglycosides to beta-lactams may protect against subsequent infections due to MDR GNB in patients with sepsis and septic shock.

In Vitro Susceptibility of Burkholderia pseudomallei Isolates to Cefiderocol and Ceftazidime/Avibactam from Odisha, India.

Introduction and Objectives The availability of a limited arsenal of antibacterial agents effective against Burkholderia pseudomallei, the causative agent of melioidosis, together with sporadic reports of emergence of resistance necessitates an evaluation of in vitro activity of new antimicrobials against clinical B. pseudomallei isolates. Cefiderocol (CFDC), a novel siderophore cephalosporin, and ceftazidime-avibactam (CZA), a new β lactam combination agent, have shown promising results for the treatment of difficult-to-treat Gram-negative bacilli infections with limited treatment options. This study was conducted to determine the in vitro activity of CFDC and CZA against a contemporary collection of 60 B. pseudomallei clinical isolates. Materials and Methods Minimum inhibitory concentrations (MIC) of CFDC and CZA were determined by broth microdilution and E-test, respectively. The performance of disk diffusion was also evaluated for CFDC. Results All B. pseudomallei isolates were susceptible to CFDC and CZA with MIC range of 0.125 to 2 mg/L and 0.19 to 1 mg/L, respectively. Zone diameters for CFDC ranged from 31 to 40 mm. Conclusion CFDC and CZA exhibited excellent in vitro activity against 60 B. pseudomallei isolates. Further pharmacokinetic-pharmacodynamics studies and clinical trials are needed to prove the clinical efficacy of CFDC and CZA in the treatment of melioidosis.

Cefiderocol Treatment for Severe Infections due to Difficult-to-Treat-Resistant Non-Fermentative Gram-Negative Bacilli in ICU Patients: A Case Series and Narrative Literature Review.

Cefiderocol (FDC) is a siderophore cephalosporin now recognized as a new weapon in the treatment of difficult-to-treat-resistant (DTR) Gram-negative pathogens, including carbapenemase-producing enterobacterales and non-fermentative Gram-negative bacilli (GNB). This article reports our experience with an FDC-based regimen in the treatment of 16 extremely severe patients (invasive mechanical ventilation, 15/16; extracorporeal membrane oxygenation, 9/16; and renal replacement therapy, 8/16) infected with DTR GNB. Our case series provides detailed insight into the pharmacokinetic profile and the microbiological data in real-life conditions. In the narrative review, we discuss the interest of FDC in the treatment of non-fermentative GNB in critically ill patients. We reviewed the microbiological spectrum, resistance mechanisms, pharmacokinetics/pharmacodynamics, efficacy and safety profiles, and real-world evidence for FDC. On the basis of our experience and the available literature, we discuss the optimal FDC-based regimen, FDC dosage, and duration of therapy in critically ill patients with DTR non-fermentative GNB infections.

Microbiologic Cure with a Simplified Dosage of Intravenous Colistin in Adults: A Retrospective Cohort Study.

Colistin's FDA weight-based dosing (WBD) and frequency are both expressed in a broad range. Therefore, a simplified fixed-dose regimen (SFDR) of intravenous colistin based on three body-weight segments has been established for adults. The SFDR falls within the WBD range of each body-weight segment and accounts for the pharmacokinetic features. This study compared microbiologic cure with colistin SFDR to WBD in critically ill adults. A retrospective cohort study was conducted for colistin orders from January 2014 to February 2022. The study included ICU patients who received intravenous colistin for carbapenem-non-susceptible, colistin-intermediate Gram-negative bacilli infections. Patients received the SFDR after the protocol was implemented, as the WBD was previously used. The primary endpoint was microbiologic cure. Secondary endpoints were 30-day infection recurrence and acute kidney injury (AKI). Of the 228 screened patients, 84 fulfilled the inclusion and matching criteria (42 in each group). The microbiologic cure rate was 69% with the SFDR and 36% with the WBD [p=0.002]. Infection recurred in four of the 29 patients who had a microbiologic cure with the SFDR (14%), and in six of the 15 patients with WBD (40%); [p=0.049]. AKI occurred in seven of the 36 SFDR patients who were not on hemodialysis (19%) and 15 of the 33 WBD patients (46%); [p=0.021]. In this study, colistin SFDR was associated with a higher microbiologic cure in carbapenem-non-susceptible, colistin-intermediate Gram-negative bacilli infections and with a lower incidence of AKI in critically ill adults compared to WBD.

Clinical features and pathogen distributions of microbiological-based protracted bacterial bronchitis in children of different ages in Northeast China.

Protracted bacterial bronchitis (PBB) is often diagnosed clinically according to chronic wet cough, which can be resolved by appropriate antibiotics. Though rarely performed in PBB diagnosis, bacterial cultures by sputum or bronchoalveolar lavage (BAL) fluid can provide etiological features, which may be different in western countries and different areas of China. This study aimed to investigate the clinical and etiological features and outcomes in children of different ages with PBB in northeast China. We retrospectively analyzed children diagnosed with PBB by positive BAL fluid or sputum bacterial cultures between 2017 and 2021. Children were divided into three age groups: <1 year (infants), 1-5 years (younger children), and ≥6 years (older children). Clinical characteristics, chest radiographic findings, bronchoscopy findings, microbiological findings, treatment strategies, and outcomes were reviewed and compared among the age groups. Factors associated with remission during follow-up were examined using logistic regression. A total of 45 children with PBB were included, consisting of 24 (53.3%) infants. The infants were often boys and had a shorter cough duration, a lower proportion of expectoration, a greater proportion of wheezing, and less bronchial wall thickening on high-resolution computed tomography compared to older children (P < 0.05). No significant differences were found among the age groups regarding macroscopic findings, except for a higher proportion of tracheobronchial malacia in infants than in older children (P = 0.013). The most commonly cultured bacteria were Haemophilus influenzae (42.2%), followed by Streptococcus pneumoniae (22.2%) and Klebsiella pneumoniae (20.0%). Compared to older children, infants had a higher remission (P = 0.009) and relatively lower relapse rates (P = 0.059). Short duration of cough (OR = 0.58, 95% CI: 0.34-0.99, P = 0.046) and absence of recurrent cephalosporins before diagnosis (OR = 0.05, 95% CI: 0.00-0.73, P = 0.028) were associated with remission. Infants are more prone to PBB, with increased wheezing. Gram-negative bacilli infections are common in infants in northeast China. Older children with PBB should be carefully assessed, treated and followed up, particularly those with long duration of cough and poor response to antibiotic treatments.

Case Report: Successful Treatment of Recurrent Urinary Tract Infection Due to Extensively Drug-Resistant Klebsiella Pneumoniae in a Kidney Transplant Recipient Using Chloramphenicol

Effective therapies for multidrug-resistant (MDR) microorganisms, especially Gram-negative bacteria, are becoming rare. Also, solid-organ transplant recipients are at high risk of MDR Gram-negative bacilli infection. Urinary tract infections are the most frequent bacterial infections in kidney transplant recipients and are an important cause of mortality after renal transplantation. We describe a case of complicated urinary tract infection in a kidney transplant patient due to extensively drug-resistant (XDR) K. pneumoniae treated successfully with a regimen comprising a combination of chloramphenicol and ertapenem. We do not recommend chloramphenicol as a first-line choice for treating complicated urinary tract infections. Still, we believe it is an alternative for infections caused by MDR and/or XDR pathogens in renal transplant patients, as other options are nephrotoxic.

Anthelmintic Drugs for Repurposing against Gram-Negative Bacilli Infections.

Bacterial infections are among the leading causes of death worldwide. The emergence of antimicrobial resistance factors threatens the efficacy of all current antimicrobial agents, with some already made ineffective, and, as a result, there is an urgent need for new treatment approaches. International organizations, such as the World Health Organization and the European Centre for Diseases Control, have recognized infections caused by multi-drug-resistant (MDR) bacteria as a priority for global health action. Classical antimicrobial drug discovery involves in vitro screening for antimicrobial candidates, Structure-Activity Relationship analysis, followed by in vivo testing for toxicity. Bringing drugs from the bench to the bedside involves huge expenditures in time and resources. This, along with the relatively short window of therapeutic application for antibiotics attributed to the rapid emergence of drug resistance, has, at least until recently, resulted in a waning interest in antibiotic discovery among pharmaceutical companies. In this environment, "repurposing" (defined as investigating new uses for existing approved drugs) has gained renewed interest, as reflected by several recent studies, and may help to speed up the drug development process and save years of expensive research invested in antimicrobial drug development. The goal of this review is to provide an overview of the scientific evidence on potential anthelmintic drugs targeting Gram-negative bacilli (GNB). In particular, we aim to: (i) highlight the potential of anthelmintic drugs for treatments of GNB infections, (ii) review their mechanisms of action against these bacteria, (iii) summarize the outcome of preclinical studies investigating approved anthelmintic drugs that target these bacteria, (iv) provide critical challenges for further anthelmintic repurposing drugs development, and (v) list the specific anthelmintic drugs that may be more likely to be repurposed.