Multidrug-resistant Gram-negative Bacilli Infections Research Articles

The Efficacy and Safety of Intravenous Colistin Plus Aerosolized Colistin Versus Intravenous Colistin Alone in Critically Ill Trauma Patients With Multi-Drug Resistant Gram-Negative Bacilli Infection.

Gram-negative bacteria (GNB) with potential multiple drug resistance (MDR) have emerged as a major group of organisms causing ventilator-associated pneumonia (VAP). Higher concentrations are deposited directly in the lungs when antibiotics are given via inhalation, minimizing systemic side effects. This study aims to compare the efficacy and safety of intravenous plus aerosolized colistin versus intravenous (IV) colistin alone in critically ill trauma patients who reported MDR-GNB infection on endotracheal aspirate culture. A hundred patients were recruited in the Intensive Care Unit, Trauma Centre, Institute of Medical Sciences, Banaras Hindu University, Varanasi, and randomly assigned to the control (n=50) group, which received IVcolistin plus aerosolized colistin and the intervention group (n = 50), which received IVcolistin alone. Changes in total leucocyte count (TLC), renal function test (RFT), endotracheal aspirate culture, 24-hour urine output, length of ICU stay, and 28-day ICU mortality were investigated. Patients receiving intravenous plus nebulized colistin therapy had a better outcome compared to IV colistin alone in terms of faster eradication of MDR-GNB infection. A rise in serum urea and creatinine levels was seen in both groups, which were significantly higher, along with a decrease in urine output in the group receiving intravenous colistin alone. No significant difference was observed in serum sodium and potassium levels in the RFT protocol, length of ICU stay, or 28-day ICU mortality. Intravenous nebulized colistin could be considered a better alternative therapy for VAP caused by multi-drug-resistant Gram-negative bacteria in the ICU in terms of faster microbiological cure and lesser nephrotoxicity.

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.

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

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

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

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

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

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

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

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

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

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

Multidrug-resistant, gram-negative infections in high-risk haematologic patients: an update on epidemiology, diagnosis and treatment.

Multidrug-resistant Gram-negative bacilli (MDR-GNB) infections are a significant cause of morbidity and mortality in high-risk hematologic patients. Early diagnosis and management of antibiotic treatment in these patients is a challenge for physicians. This review focuses on the latest literature reports that concern the epidemiology, diagnosis and treatment of MDR-GNB infections in this population. High-risk haematological patients have several risk factors that make them particularly susceptible to MDR-GNB infections. Few studies have examined the implementation of rapid diagnostic methods for multidrug resistance, and their impact on management in this population. Inappropriate empiric antibiotic treatment in these patients has been described frequently and is associated with poor outcomes. Knowledge of the local epidemiology of MDR-GNB is a basic requirement to guide empiric antibiotic treatments in each centre. New diagnosic tests might help in faster identification of MDR-GNB infections. Appropriate empiric antibiotic treatment is crucial for improving patients' prognosis. Important strategies to reduce inadequate antibiotic treatment include better risk stratification for MDR-GNB infection and the introduction of new, more broad-spectrum antibiotic therapies.

Colistin resistance genes mcr-1 to mcr-5, including a case of triple occurrence (mcr-1, -3 and -5), in Escherichia coli isolates from faeces of healthy pigs, cattle and poultry in Belgium, 2012–2016

Colistin is a last-resort antimicrobial used to treat infections caused by multidrug-resistant Gram-negative bacilli (MDR-GNB). The emergence of colistin resistance, particularly linked to mobile genetic elements including the mcr genes, is a major threat to the management of MDR-GNB infections. The aim of this study was to assess the presence of mcr genes in a collection of 40 colistin-resistant commensal Escherichia coli isolated from healthy pigs, cattle and poultry in Belgium between 2012 and 2016. All isolates carried at least one mcr gene. The genes mcr-1 to -5 were observed in this collection. Different replicons associated with mcr genes were identified, including IncHI2/IncHI2A associated with mcr-1, IncX4 associated with mcr-1 and mcr-2, and ColE10 associated with mcr-4. While the occurrence of multiple mcr genes in a single isolate has rarely been reported elsewhere, a triple occurrence (mcr-1, -3 and -5) was found in this study. All isolates were MDR and carried between one and nine different replicons. Seventeen different sequence types were observed among the 40 E. coli isolates. In conclusion, this study revealed the presence of a reservoir of mobile colistin resistance genes (mcr-1 to -5) observed during at least 5 years (2012-2016) in the commensal gut flora of pigs, cattle and poultry in Belgium.

Machine Learning to Assess the Risk of Multidrug-Resistant Gram-Negative Bacilli Infections in Febrile Neutropenic Hematological Patients.

IntroductionWe aimed to assess risk factors for multidrug-resistant Gram-negative bacilli (MDR-GNB) from a large amount of data retrieved from electronic health records (EHRs) and determine whether machine learning (ML) may be useful in assessing the risk of MDR-GNB infection at febrile neutropenia (FN) onset.MethodsRetrospective study of almost 7 million pieces of structured data from all consecutive episodes of FN in hematological patients in a tertiary hospital in Barcelona (January 2008–December 2017). Conventional multivariate analysis and ML algorithms (random forest, gradient boosting machine, XGBoost, and GLM) were done.ResultsA total of 3235 episodes of FN in 349 patients were documented; MDR-GNB caused 180 (5.6%) infections in 132 patients. The most frequent MDR-GNBs were MDR-Pseudomonas aeruginosa (53%) and extended-spectrum beta-lactamase-producing Enterobacterales (46%). According to conventional logistic regression analysis, independent factors associated with MDR-GNB infection were age older than 45 years (OR 2.07; 95% CI 1.31–3.24), prior antibiotics (2.62; 1.39–4.92), first-ever FN in this hospitalization (2.94; 1.33–6.52), prior hospitalizations for FN (1.72; 1.02–2.89); at least 15 prior hospital visits (2.65; 1.31–5.33), high-risk hematological diseases (3.62; 1.12–11.67), and hospitalization in a room formerly occupied by patients with MDR-GNB isolation (1.69; 1.20–2.38). ML algorithms achieved the following AUC and F1 score for MDR-GNB prediction: random forest, 0.79–0.9711; GMB, 0.79–0.9705; XGBoost, 0.79–0.9670; and GLM, 0.78–0.9716.ConclusionData generated in EHRs proved useful in assessing risk factors for MDR-GNB infections in patients with FN. The great number of analyzed variables allowed us to identify new factors related to MDR infection, as well as to train ML algorithms for infection predictions. This information may be used by clinicians to make better clinical decisions.

Validating a prediction tool to determine the risk of nosocomial multidrug-resistant Gram-negative bacilli infection in critically ill patients: A retrospective case–control study

BackgroundThe Singapore GSDCS score was developed to enable clinicians predict the risk of nosocomial multidrug-resistant Gram-negative bacilli (RGNB) infection in critically ill patients. We aimed to validate this score in a UK setting. MethodA retrospective case–control study was conducted including patients who stayed for more than 24h in intensive care units (ICUs) across two tertiary National Health Service hospitals in London, UK (April 2011–April 2016). Cases with RGNB and controls with sensitive Gram-negative bacilli (SGNB) infection were identified. ResultsThe derived GSDCS score was calculated from when there was a step change in antimicrobial therapy in response to clinical suspicion of infection as follows: prior Gram-negative organism, Surgery, Dialysis with end-stage renal disease, prior Carbapenem use and intensive care Stay of more than 5 days. A total of 110 patients with RGNB infection (cases) were matched 1:1 to 110 geotemporally chosen patients with SGNB infection (controls). The discriminatory ability of the prediction tool by receiver operating characteristic curve analysis in our validation cohort was 0.75 (95% confidence interval 0.65–0.81), which is comparable with the area under the curve of the derivation cohort (0.77). The GSDCS score differentiated between low- (0–1.3), medium- (1.4–2.3) and high-risk (2.4–4.3) patients for RGNB infection (P<0.001) in a UK setting. ConclusionA simple bedside clinical prediction tool may be used to identify and differentiate patients at low, medium and high risk of RGNB infection prior to initiation of prompt empirical antimicrobial therapy in the intensive care setting.

Emergence of colistin and carbapenem-resistant Acinetobacter calcoaceticus-Acinetobacter baumannii (CCR-Acb) complex in a neurological intensive care unit followed by successful control of the outbreak

BackgroundColistin and carbapenem-resistant Acinetobacter calcoaceticus- Acinetobacter baumannii complex (CCR-Acb complex) was isolated from two consecutive patients in the neurological intensive care unit (NICU). An urgent reaction to this desperate situation was required. Patients and methodsScreening cultures were taken from the other patients sharing the NICU with index patients and repeated periodically. NICU was closed for new admissions. Infection control precautions (ICP) such as hand hygiene, cohorting patients colonized with CCR-Acb complex, cohorting the staff caring for these patients, daily bathing with chlorhexidine gluconate impregnated clothes, using gowns when contacting with patients and patient care area, and sodium hypochlorite tablets for environmental cleaning were enforced. ResultsScreening cultures revealed carbapenem-resistant Acb complex in 12 out of 32 patients and 8 of them were colonized with CCR-Acb complex. NICU was opened for new admissions one month later. No further new cases with CCR-Acb complex were detected by screening cultures after 6 weeks with enforcement of ICP. Moreover, the rate of nosocomial infections caused by other multi-drug resistant Gram-negative bacilli (MDR-GNB) decreased significantly when rates before and after closing the NICU were compared. ConclusionICP were effective not only to limit the spread of CCR-Acb complex but also decreased the incidence of other MDR-GNB infections when applied adequately.

First three Escherichia coli isolates harbouring mcr-1 in Uruguay.

This report described the first Escherichia coli (E. coli) isolates harbouring mcr-1 in Uruguay. Three E. coli isolates were obtained from blood, urine and rectal swabs from different patients in two hospitals. Extended-spectrum β-lactamases (ESBL), plasmid-encoded (pAmpC) β-lactamases, plasmid-mediated quinolone resistance (PMQR) genes, class 1 integrons, and mcr-1, mcr-2 and mcr-3 were sought and characterised in three E. coli isolates. Transfer of resistance determinants was assessed by conjugation. Clonality was analysed by multilocus sequence typing. All isolates were categorised as being colistin-resistant and the mcr-1 gene was detected. Two isolates were also resistant to oxyimino cephalosporins: one on account of blaCMY-2 and the other due to blaCTX-M-15, the latter also harbouring transferable quinolone-resistance genes (aac(6')Ib-cr and qnrB). All mcr-1 genes were transferred by conjugation to recipient strains. The mcr-1-bearing isolates belonged to sequence types ST10, ST93 and ST5442. ST10 is considered as a high-risk clone worldwide. This type of mcr-1-harbouring clone is a major concern for human and animal health and must be under close surveillance. This study detected the presence of mcr-1 for the first time in Uruguay, albeit in an allodemic manner, associated with different antibiotic-resistance genes and from diverse clinical contexts. Considering that colistin is often the last therapeutic option available for multidrug-resistant Gram-negative bacilli infections, it is important to maximise precautions to avoid dissemination of isolates carrying mcr-1.

Multidrug-resistant Gram-negative infection in solid organ transplant recipients: implications for outcome and treatment.

Solid organ transplantation (SOT) is the best therapeutic option for both acute and chronic end-stage diseases. The development of more potent and safer immunosuppressants and the improvement of prophylactic practices have significantly diminished the morbidity and mortality associated with rejection and opportunistic infections. However, infections produced by multidrug-resistant (MDR) Gram-negative bacilli (GNB) have recently emerged as a significant threat. The Spanish Society of Transplantation (SET), the Group for Study of Infection in Transplantation of the Spanish Society of Infectious Diseases and Clinical Microbiology (GESITRA-SEIMC) and the Spanish Network for Research in Infectious Diseases (REIPI) have recently published their recommendations concerning the management of MDR GNB infections in SOT recipients. We review this guideline, and also the most recent available evidence, focusing on donor-derived infections, colonized recipients and therapeutic approaches. Overall, donor and recipient colonization is associated with an increased risk of infection by MDR GNB, although none of these circumstances constitutes an absolute contraindication to transplantation. SOT recipients with risk factors for MDR GNB infection should receive an empirical treatment which includes potentially active antibiotics. Targeted therapy should be adjusted according to antimicrobial susceptibility testing and severity of infection.

Efficacy and Safety of Intravenous Colistin in Very Low Birth Weight Preterm Infants.

Given the severity and high mortality of multidrug-resistant Gram-negative bacilli (MDR-GNB) infections, the use of colistin will increase in patients with MDR-GNB infection. This study aims to assess the efficacy and safety of intravenous colistin in very low birth weight (VLBW; birth weight < 1500g) preterm infants. We retrospectively analyzed the medical records of patients who received colistin between June 2016 and December 2017. The patients were assigned to two groups: the VLBW group and the non-VLBW group. Both groups were evaluated for response to treatment and adverse effects. In total, 66 infants who received colistin therapy were included; of these, 28 infants were VLBW. All of our patients received standard colistin treatment of 5mg/kg per day in three doses and the median duration of colistin treatment was 14days. No significant differences were observed between the groups with respect to the efficacy of colistin (defined as showing microbiological clearance in control cultures and the absence of mortality during treatment) (89.3 vs 86.8%, p>0.99). Serum magnesium and potassium levels were significantly lower in the VLBW group than in the non-VLBW group during colistin therapy (magnesium, 1.30 vs 1.70mg/dL, p<0.001; potassium, 3.6 vs 4.6mEq/L, p<0.001). Acute kidney injury was observed in four infants in the VLBW group and one in the non-VLBW group, without significant differences (p=0.15). Colistin administration appears to be efficacious in VLBW infants; however, renal function tests and serum electrolytes should be monitored more closely in these infants during treatment.

Management of multidrug resistant Gram-negative bacilli infections in solid organ transplant recipients: SET/GESITRA-SEIMC/REIPI recommendations.

Solid organ transplant (SOT) recipients are especially at risk of developing infections by multidrug resistant (MDR) Gram-negative bacilli (GNB), as they are frequently exposed to antibiotics and the healthcare setting, and are regulary subject to invasive procedures. Nevertheless, no recommendations concerning prevention and treatment are available. A panel of experts revised the available evidence; this document summarizes their recommendations: (1) it is important to characterize the isolate's phenotypic and genotypic resistance profile; (2) overall, donor colonization should not constitute a contraindication to transplantation, although active infected kidney and lung grafts should be avoided; (3) recipient colonization is associated with an increased risk of infection, but is not a contraindication to transplantation; (4) different surgical prophylaxis regimens are not recommended for patients colonized with carbapenem-resistant GNB; (5) timely detection of carriers, contact isolation precautions, hand hygiene compliance and antibiotic control policies are important preventive measures; (6) there is not sufficient data to recommend intestinal decolonization; (7) colonized lung transplant recipients could benefit from prophylactic inhaled antibiotics, specially for Pseudomonas aeruginosa; (8) colonized SOT recipients should receive an empirical treatment which includes active antibiotics, and directed therapy should be adjusted according to susceptibility study results and the severity of the infection.

Multi-Drug-Resistant Gram-Negative Infections in Deployment-Related Trauma Patients.

The contribution of multi-drug-resistant gram-negative bacilli infections (MDRGN-I) in patients with trauma is not well described. We present characteristics of MDRGN-Is among military personnel with deployment-related trauma (2009-2014). Data from the Trauma Infectious Disease Outcomes Study were assessed for infectious outcomes and microbial recovery. Infections were classified using standardized definitions. Gram-negative bacilli were defined as multi-drug-resistant if they showed resistance to ≥3 antibiotic classes or were producers of extended-spectrum β-lactamase or carbapenemases. Among 2,699 patients admitted to participating U.S. hospitals, 913 (33.8%) experienced ≥1 infection event, of which 245 (26.8%) had a MDRGN-I. There were 543 MDRGN-I events (24.6% of unique 2,210 infections) with Escherichia coli (48.3%), Acinetobacter spp. (38.6%), and Klebsiella pneumoniae (8.4%) as the most common MDRGN isolates. Incidence of MDRGN-I was 9.1% (95% confidence interval [CI]: 8.0-10.2). Median time to MDRGN-I event was seven days with 75% occurring within 13 days post-trauma. Patients with MDRGN-Is had a greater proportion of blast injuries (84.1% vs. 62.5%; p < 0.0001), traumatic amputations (57.5% vs. 16.3%; p < 0.0001), and higher injury severity (82.0% had injury severity score ≥25 vs. 33.7%; p < 0.0001) compared with patients with either no infections or non-MDRGN-Is. Furthermore, MDRGN-I patients were more frequently admitted to the intensive care unit (90.5% vs. 48.5%; p < 0.0001), colonized with a MDRGN before infection (58.0% vs. 14.7%; p < 0.0001), and required mechanical ventilation (78.0% vs. 28.8% p < 0.0001). Antibiotic exposure before the MDRGN-I event was significantly higher across antibiotic classes except first generation cephalosporins and tetracyclines, which were very commonly used with all patients. Regarding outcomes, patients with MDRGN-Is had a longer length of hospitalization than the comparator group (53 vs. 18 days; p < 0.0001). We found a high rate of MDRGN-I in our population characterized by longer hospitalization and greater injury severity. These findings inform treatment and infection control decisions in the trauma patient population.

Use of Colistin in a Neonatal Intensive Care Unit: A Cohort Study of 65 Patients.

BackgroundThe emergence of infections related to multidrug-resistant Gram-negative bacilli (MDR-GNB) reintroduced the use of colistin, an antibiotic that was previously abandoned due to adverse effects. However, because of its limited use in neonatal intensive care units, there is very little data about the effectiveness and safety of colistin in children and newborns. In this study, which will be the largest case study in the literature, we aimed to evaluate the effectiveness and safety of colistin in full-term and preterm newborns.Material/MethodsThe study included patients admitted into 2 level 3 neonatal intensive care units between January 2013 and June 2015. The medical records of patients diagnosed with sepsis, meningitis, pneumonia, and urinary tract infection based on the diagnostic culture results and treated with colistin were analyzed retrospectively. The patients whose infections were not verified were excluded from the study.ResultsThe study included 65 patients (18 term, 47 preterm). The most frequently isolated pathogens were Klebsiella pneumoniae and Acinetobacter baumannii followed by Pseudomonas aeruginosa and Enterobacter cloacae. Mean colistin treatment time was 15±3.5 days. All patients treated with colistin were being treated with at least 1 other antibiotic. While a complete clinical response was achieved in 51 (72.3%) patients, 14 (21.5%) patients died during treatment. Four (7.7%) patients died during as a result of another infection. Three patients developed renal toxicity, another 3 patients had seizures, and apnea was observed in 3 patients.ConclusionsColistin was found to be effective and safe for treatment of MDR-GNB infections in preterms and infants with very low birth weight. Given the severity of the infection, the adverse effects of colistin were at acceptable levels.

Intravenous Colistin Use for Multidrug-Resistant Gram-Negative Infections in Pediatric Patients.

The emergence of infections due to multidrug-resistant Gram-negative bacilli (MDR-GNB) has led to the resurrection of colistin use. The data on colistin use and drug-related adverse effects in children are scarce. In this study, we aimed to evaluate the clinical efficacy and safety of colistin use in critically ill pediatric patients. This study has a retrospective study design. Sixty-one critically ill children were identified through the department's patient files archive during the period from January 2011 to November 2014. Twenty-nine females and thirty-two males with a mean±standard deviation (SD) age of 61±9 months (range 0-216, median 12 months) received IV colistin due to MDR-GNB infections. Bacteremia (n=23, 37.7%) was the leading diagnosis, followed by pneumonia (n=19, 31%), clinical sepsis (n=7, 11.4%), wound infection (n=6, 9.8%), urinary tract infection (n=5, 8.1%) and meningitis (n=1, 1.6%). All of the isolates were resistant to carbapenems; however, all were susceptible to colistin. The isolated microorganisms in decreasing order of frequency were: Acinetobacter baumanni (n=27, 44.2%), Pseudomonas aeruginosa (n=17, 27.8%), Klebsiella pneumoniae (n=6, 9.8%), K. pneumoniae and Stenotrophomonas maltophilia (n=1, 1.6%), K. pneumoniae and A. baumanni (n=1, 1.6%), K. oxytoca (n=1, 1.6%) and Enterobacter cloacae (n=1, 1.6%). In seven patients, no microorganisms were detected; however, five of these patients were colonized by carbapenem-resistant K. pneumoniae. The mean duration of colistin therapy was 12 days (range 3-45). Colistin was administered concomitantly with one of the following antibiotics: carbapenem (n=50, %82), ampicillin-sulbactam (n=5, 8%), quinolones (n=5, 8%), rifampicin (n=1, 1.6%). Carbapenem was the most frequently used antibiotic. Nephrotoxicity was observed in only 1 patient, and we did not observe neurotoxicity in this study. All the patients received intravenous colistin (colisthimethate) at a dosage of 5 mg/kg daily by dividing it in three equal doses. Seven (11.4%) patients died during the study period. Colistin appears to be a safe and efficacious drug for treating MDR-GNB infections in children.

Efficacy and Toxicity of High-Dose Colistin in Multidrug-Resistant Gram-Negative Bacilli Infections: A Comparative Study of a Matched Series

Background: Colistimethate sodium (CMS) is the commercialized form of colistin that is effective against multiresistant Gram-negative bacilli. Its main side effects are nephrotoxicity and neurotoxicity. Pharmacodynamic dosages showed that they were infratherapeutic. Therefore, strategies with higher doses were proposed. The aim of this study was to assess the efficiency and toxicity of higher-dose CMS by comparing two treatment strategies: high-dose CMS versus standard-dose CMS. Methods: A prospective and comparative study of two matched groups was conducted. Fourty-six patients in each group were matched for age, severity and nature of infection. In the high-dose colistin group, CMS was administered at a loading dose of 9 MIU followed by a maintenance dose of 4.5 MIU/12 h. In the second group, retrospectively analyzed, colistin was administered at 6 MIU/day. For each group, clinical results, bacteriological eradication and daily creatinine clearance were recorded. Primary outcome measures were clinical cure defined as disappearance of infectious signs and eradication of microorganisms in all the follow-up cultures. Secondary outcome measures were incidence of acute renal failure and mortality. Results: Ninety-two patients were analyzed by matching. There was a higher cure rate in the high-dose group (63 vs. 41.3%, p = 0.04). No higher risk of nephrotoxicity was found by increasing daily doses of colistin (32.2 versus 26%, p = 0.64). Similarly, there was no significant difference in the time to onset of renal failure (8.32 vs. 11 days, p = 1) or in the requirement of hemodialysis (26.6 vs. 41%, p = 1). Conclusion: The high-dose colistin regimen is more efficient, without significant renal or neurological toxicity.