The association of acute kidney injury with the concomitant use of vancomycin and piperacillin/tazobactam in children: A systematic review and meta-analysis.

Concomitant use of vancomycin plus piperacillin/tazobactam (TZP) has been associated with increased risk of acute kidney injury (AKI) in hospitalized adults. In this systematic review and meta-analysis, we searched PubMed and EMBASE for pediatric studies examining this hypothesis, with reference to vancomycin monotherapy or in combination with another beta-lactam antibiotic. Out of 1381 non-duplicate studies, 10 met our inclusion criteria. We performed a random effects meta-analysis, based on crude odds ratios, and we accounted for both quality of included studies and publication bias. In primary analysis, concomitant vancomycin and TZP use yielded a statistically significant association with the development of AKI. More specifically, children with AKI had higher odds to have been exposed to vancomycin plus TZP, in comparison with vancomycin monotherapy (OR 8.15; 95% CI: 3.49-18.99), or vancomycin plus any other beta-lactam antibiotic (OR 3.48; 95% CI: 2.71-4.46). Based on the results of the Newcastle Ottawa Scale quality assessment, a secondary analysis including only higher quality studies (6 out of 10 studies) yielded again higher odds of exposure to vancomycin plus TZP, compared to vancomycin plus another beta-lactam antibiotic (OR 3.76; 95% CI: 2.56-5.51). Notably, even after controlling for possible publication bias our results remained statistically significant (OR 3.09; 95% CI: 2.30-4.14). In conclusion, the concomitant use of vancomycin and TZP could be associated with AKI development and the clinical significance of this potential association needs to be studied further in the pediatric population.

Intravenous colistin use for infections due to MDR Gram-negative bacilli in critically ill paediatric patients: a systematic review and meta-analysis.

BACKGROUND: Data are limited regarding the clinical effectiveness and safety of intravenous colistin for treatment of infections due to MDR Gram-negative bacilli (GNB) in paediatric ICUs (PICUs). METHODS: Systematic review of intravenous colistin use in critically ill paediatric patients with MDR-GNB infection in PubMed, Scopus and EMBASE (up to 31 January 2018). RESULTS: Out of 1181 citations, 7 studies were included on the use of intravenous colistin for 405 patients in PICUs. The majority of patients were diagnosed with lower respiratory tract infections, Acinetobacter baumannii being the predominant pathogen. Colistin dosages ranged between 2.6 and 18 mg/kg/day, with only one case reporting a loading dose. Emergence of colistin resistance during treatment was reported in two cases. Nephrotoxicity and neurotoxicity were reported in 6.1% and 0.5%, respectively, but concomitant medications and severe underlying illness limited our ability to definitively associate use of colistin with nephrotoxicity. Crude mortality was 29.5% (95% CI = 21.7%-38.1%), whereas infection-related mortality was 16.6% (95% CI = 12.2%-21.5%). CONCLUSIONS: While the reported incidence of adverse events related to colistin was low, reported mortality rates for infections due to MDR-GNB in PICUs were notable. In addition to severity of disease and comorbidities, inadequate daily dosage and the absence of a loading dose may have contributed to mortality. As the use of colistin for treatment of MDR-GNB infections increases, it is imperative to understand whether optimal dosing of colistin in paediatric patients differs across different age groups. Thus, future studies to establish the pharmacokinetic properties of colistin in different paediatric settings are warranted.

Geoepidemiology of hepatocellular carcinoma in the island of Crete, Greece. A possible role of pesticides.

BACKGROUND & AIMS: Geoepidemiological data of hepatocellular carcinoma (HCC) are lacking. Crete has a genetically homogeneous population and is suitable for studies to identify a possible contribution of environmental factors in HCC. METHODS: Databases for HCC (316 cases), hepatitis B virus (HBV) (633) and hepatitis C virus (HCV) (392), constructed over the past 20 years in our Unit, were used. Data included place of birth and place of residence for the last 15 years. Hellenic Statistical Authority provided population statistics from 1980 to 2014. Time-spatial methods were applied in Gis-ArcMap 10 software. Spatial autocorrelation tests (Moran's index) detected differences between the spatial distribution to place of residence. Spatial density maps were created. Kriging Interpolation was applied, to produce prediction maps of HCC. RESULTS: Hepatitis C virus appears in areas of high prevalence while HBV is uniformly distributed. HCC is more prevalent in Eastern Crete. A spatial autocorrelation between HCC and either HCV (Moran's I = 0.88, P < 0.001) or HBV (I = 0.84, P < 0.02) was found as expected. However, there is a discrepancy in the South East of Crete, where a higher prevalence of HCC than expected was observed. This is an area where extensive use of pesticides in large green houses is practiced. CONCLUSIONS: Hepatocellular carcinoma is associated with the dispersion of HCV and HBVs. In an area with widespread use of pesticides, a higher than expected spatial distribution of HCC was detected.

Infection Prevention and Control: Practical and Educational Advances.

Infection prevention and control (IPC) is associated with improved healthcare, better quality of life and cost-effectiveness in disease prevention [...].

Medical students' attitudes and perceptions of influenza and SARS-CoV-2 vaccination in Cyprus.

Introduction: Infectious diseases constitute a significant problem globally and healthcare professionals (HCP) show suboptimal vaccination rates. We aimed to evaluate the determinants affecting vaccination against influenza and SARS-CoV-2 among medical students in Cyprus. Methods: We conducted a cross-sectional study based on a self-reported, anonymous questionnaire that was sent to all medical students of two Medical Schools in the Republic of Cyprus. Results: Among 266 respondents, 50.8% had been vaccinated against influenza in the past and 20.1% in 2020-21. The majority believed that influenza and SARS-CoV-2 vaccines are safe and effective. Regarding vaccination in Cyprus, 41.3% did not know the current recommendations and a higher proportion of preclinical students replied incorrectly, compared to clinical students. Slightly over half (56.4%) considered themselves adequately informed about influenza vaccination, with more clinical students appearing confident (p=0.068). An overwhelming 71.2% were concerned about contracting SARS-CoV-2, compared to 25.4% with regards to influenza. Up to 76.8% considered themselves adequately informed about SARS-CoV-2 vaccination, with significantly more clinical students being confident (p<0.001). Although more preclinical students appeared hesitant, most students had either been vaccinated against SARS-CoV-2 (49.4%) or would be as soon as possible (32.1%). Vaccination refusal was 2.3%, a group comprised entirely of preclinical students. Conclusions: Our study provides relevant and actionable information about differences in attitudes and perceptions between clinical and preclinical medical students regarding vaccination against influenza and SARS-CoV-2 and highlights the importance of organized, systemic efforts to increase vaccination coverage.

Presence of Methicillin-Resistant Staphylococcus aureus (MRSA) on Healthcare Workers' Attire: A Systematic Review.

Contaminated healthcare workers' (HCW) clothing risk transferring methicillin-resistant Staphylococcus aureus (MRSA) in healthcare facilities. We performed a systematic review in Pubmed and Scopus for 2000-2020 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines to analyze evidence of MRSA on HCW attire. The primary study outcome was MRSA isolation rates on HCW clothing in healthcare settings. Out of 4425 articles, 23 studies were included: 18 with 1760 HCWs, four with 9755 HCW-patient interactions and one with 512 samples. There was a notable variation in HCWs surveyed, HCW attires, sampling techniques, culture methods and laundering practices. HCW attire was frequently colonized with MRSA with the highest rates in long-sleeved white coats (up to 79%) and ties (up to 32%). Eight studies reported additional multidrug-resistant bacteria on the sampled attire. HCW attire, particularly long-sleeved white coats and ties, is frequently contaminated with MRSA. Banning certain types and giving preference to in-house laundering in combination with contact precautions can effectively decrease MRSA contamination and spread.

Antifungal activity of amniotic fluid against different Candida species.

BACKGROUND: Although Candida is a commensal of the urogenital tract, intrauterine fungal infections are extremely uncommon in clinical practice. AIMS: In the present work we evaluated whether amniotic fluid (AF) possesses direct antifungal activity against clinical isolates of Candidaalbicans and other Candida species. METHODS: A total of 23 AF samples from pregnant women with gestational age of 38-41 weeks were obtained under aseptic conditions by the aspiration of the amniotic sac during cesarean section. Different Candida species were inoculated in amniotic fluid and Sabouraud broth, used as control, and were incubated at 37°C for 48h. Quantitative cultures of test samples and controls were performed at 0, 4, 8, 12, 24, and 48h. RESULTS: AF collected from 23 pregnant women had consistent and significant inhibitory activity against all Candida isolates tested. Nonetheless, a complete inhibition of growth by all 23 AF samples tested was observed only against Candida glabrata. CONCLUSIONS: It is likely that the antifungal activity of the AF against C. albicans, C. glabrata and Candida parapsilosis observed in vitro also exists in vivo, contributing to protect against intrauterine fungal infections.

Multidrug-Resistant Bacteria on Healthcare Workers' Uniforms in Hospitals and Long-Term Care Facilities in Cyprus.

Healthcare workers' (HCW) clothing has been shown to harbor multidrug-resistant bacteria (MDRB) and may contribute to transmission. The aim of this study was to evaluate presence of MDRB on HCW uniforms in Cyprus. A cross-sectional study was carried out in 9 hospital wards and 7 long-term care facilities (LTCFs) in Nicosia, Cyprus, from April-August 2019. Sampling of HCW uniform pockets was conducted at the end of the first shift. Personal hygiene and other habits were recorded during personal interviews. Among 140 sampled HCW (69 from hospitals, 71 from LTCFs), 37 MDRB were identified, including 16 vancomycin-resistant enterococci (VRE), 15 methicillin-resistant Staphylococcus aureus (MRSA), 5 extended spectrum b-lactamase (ESBL)-producing bacteria, and 1 carbapenem-resistant Acinetobacter baumannii. Presence of MDRB was higher in LTCFs compared to hospitals (p = 0.03). Higher MDRB rates in uniforms were noted in HCWs that worked <1 year (41.7% vs. 21.1%) and in HCWs that opted for home laundering (23.5% vs. 12.5%) or visited the toilet during shifts (38.1% vs. 20.2%). Our findings indicate that HCW uniforms harbor MDRB and relevant interventions may reduce transmission risk. We identified LTCFs as an important area for targeted measures. Additional factors associated with HCW practices, characteristics, and attire laundering practices represent areas for improvement, particularly in LTCFs.

Antibiotic Use and Antibiotic Resistance: Public Awareness Survey in the Republic of Cyprus.

We aimed to assess the knowledge and understanding of antibiotic use and resistance in the general population of Cyprus, in order to inform future antibiotic awareness campaigns with local evidence. Cross-sectional survey following the methodology of the "Antibiotic resistance: Multi-country public awareness survey" of the World Health Organization, during December 2019-January 2020. A total of 614 respondents participated: 64.3% were female and most were aged 35-44 years (33.2%) or 25-34 years (31.8%). One-third had used antibiotics >1 year ago and 91.6% reported receiving advice on appropriate use from a medical professional. Despite high awareness on correct use of antibiotics, lack of knowledge was noted for specific indications, where approximately one-third believed that viral infections respond to antibiotics and 70.7% lack understanding of how antibiotic resistance develops. Higher education graduates exhibited significantly higher knowledge rates. As high as 72.3% were informed about "antibiotic resistant bacteria" from healthcare professionals or social media. Most agreed on the usefulness of most suggested actions to address antibiotic resistance, with higher proportions acknowledging the role of prescribers. Up to 47% could not identify their role in decreasing antibiotic resistance. Our study provides local evidence to inform future efforts in a country characterized by high antibiotic consumption rates.

Enhancing Neuroblastoma Immunotherapies by Engaging iNKT and NK Cells.

Neuroblastoma (NB) is the most common extracranial solid tumor in children and, in the high-risk group, has a 5-year mortality rate of ~50%. The high mortality rate and significant treatment-related morbidities associated with current standard of care therapies belie the critical need for more tolerable and effective treatments for this disease. While the monoclonal antibody dinutuximab has demonstrated the potential for immunotherapy to improve overall NB outcomes, the 5-year overall survival of high-risk patients has not yet substantially changed. The frequency and type of invariant natural killer T cells (iNKTs) and natural killer cells (NKs) has been associated with improved outcomes in several solid and liquid malignancies, including NB. Indeed, iNKTs and NKs inhibit tumor associated macrophages (TAMs) and myeloid derived suppressor cells (MDSCs), kill cancer stem cells (CSCs) and neuroblasts, and robustly secrete cytokines to recruit additional immune effectors. These capabilities, and promising pre-clinical and early clinical data suggest that iNKT- and NK-based therapies may hold promise as both stand-alone and combination treatments for NB. In this review we will summarize the biologic features of iNKTs and NKs that confer advantages for NB immunotherapy, discuss the barriers imposed by the NB tumor microenvironment, and examine the current state of such therapies in pre-clinical models and clinical trials.

MRSA colonization and acquisition in the burn unit: A systematic review and meta-analysis.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most commonly encountered bacteria in the burn unit. In order to investigate the magnitude of this challenge, we assessed the prevalence of MRSA colonization on admission and the incidence of MRSA acquisition within burn units. METHODS: We searched PubMed and EMBASE for studies reporting MRSA colonization among patients admitted in burn units. RESULTS: We identified 16 articles that fulfilled our inclusion criteria and found an overall pooled prevalence of MRSA colonization upon the first 72 h of admission (colonization on admission) to the burn unit of 4.1% (95% CI: 2.7%-5.7%). MRSA acquisition in studies without a decolonization protocol was 21.2% (95% CI: 13.2%-30.5%) with a statistically significant downward trend over the years. Studies that implemented a decolonization protocol yielded a MRSA acquisition incidence rate of 4.5% (95% CI: 0.9%-10.6%). MRSA acquisition was higher among patients that have had inhalation injury (OR 3.96, 95% CI: 2.51-6.23), flame burns (OR 1.85, 95% CI: 1.25-2.73), or ICU admission (OR 3.12, 95% CI: 2.18-4.47). CONCLUSION: Our study yielded that among burn victims, MRSA colonization prevalence on admission is not negligible and the risk of becoming MRSA colonized during hospitalization is higher when no decolonization protocols are implemented. Flame burns, admission to ICU, and inhalation injury were found to be associated with MRSA acquisition.

Hospital-Acquired Hyponatremia in Children Following Hypotonic versus Isotonic Intravenous Fluids Infusion.

Hypotonic solutions have been used in pediatrics for maintenance of intravenous (IV) hydration. However, recent randomized control trials and cohort studies have raised significant concerns for association with hospital-acquired hyponatremia (HAH). The study aimed to assess whether the use of hypotonic parenteral solutions (PS) compared with isotonic PS is associated with increased HAH risk in children with common pediatric conditions. Retrospective chart review of 472 patients aged 2 months to 18 years who received either isotonic or hypotonic PS as maintenance fluids. Administration of hypotonic PS was associated with a four-fold increase in risk of developing HAH in the univariate analysis, (unadjusted odds ratio (OR) = 3.99; 95% confidence interval (CI): 1.36⁻11.69, p = 0.01). Hypotonic PS were associated with HAH (p = 0.04) when adjusted for the level of admission serum CO2. There was a mean decrease of serum sodium of 0.53 mEq/L in the hypotonic group compared to the mean increase of 4.88 mEq/L in the isotonic group. These data suggest that hypotonic PS are associated with HAH in children admitted for common pediatric conditions. Isotonic PS should be considered as a safer choice for maintenance fluid hydration.

Vancomycin-resistant enterococci colonisation, risk factors and risk for infection among hospitalised paediatric patients: a systematic review and meta-analysis.

The objective of this study was to estimate the rate and significance of colonisation with vancomycin-resistant enterococci (VRE) among hospitalised children. The PubMed and EMBASE databases were systematically searched (last accessed on 29 May 2016) to identify studies evaluating VRE colonisation of the gastrointestinal tract of hospitalised children in non-outbreak periods. Of 945 non-duplicate citations, 19 studies enrolling 20 234 children were included. The overall and paediatric intensive care unit (PICU) rate of VRE colonisation were both 5% [95% confidence interval (CI) 3-8% overall and 95% CI 2-9% in the PICU] but was 23% in haematology/oncology units (95% CI 18-29%). Studies that were exclusively performed in haematology/oncology units reported significantly higher rates compared with all other studies in the univariate and multivariate analyses (P = 0.001). Previous vancomycin [risk ratio (RR) = 4.34, 95% CI 2.77-6.82] or ceftazidime (RR = 4.15, 95% CI 2.69-6.40) use was a risk factor for VRE colonisation. Importantly, VRE colonisation increased the risk of subsequent VRE infection (RR = 8.75, 95% CI 3.19-23.97). In conclusion, a high rate of VRE colonisation was found among hospitalised children in institutions that performed targeted screening. Importantly, colonised children were almost 9 times more likely to develop subsequent VRE infection. Judicious use of specific antibiotics along with intensification of infection control measures should be considered in high-prevalence institutions. Also, the high incidence of VRE colonisation among children with haematological/oncological diseases identifies a high-risk population.

Factors Associated with HIV Testing and HIV Treatment Adherence: A Systematic Review.

BACKGROUND: The impact of the global economic crisis on HIV-related access and care remains unclear. The objective of this systematic review of the literature was to evaluate the association between socioeconomic factors and HIV diagnosis, and adherence to treatment, following the 2008 global economic crisis. METHOD: A systematic search of PubMed and Scopus for studies published between January 2008 and October 2016 was conducted. Studies providing data on social, demographic, economic and cultural barriers associated with HIV diagnosis and treatment were included. RESULTS: Of 33 studies included, 22 evaluated HIV testing and 11 evaluated treatment adherence. Medical history of a sexually transmitted disease, knowledge of HIV-related risks, and age, were significantly associated with HIV testing in most of the included studies. Absence of social support, and alcohol or substance use, were the most common factors associated with adherence. Financial factors were not as commonly found to be related to access to HIV diagnosis and HIV treatment adherence, compared to knowledge of HIV-related risks and social support. CONCLUSION: The identification of persons who are less likely to test for HIV, and to adhere to HIV treatment, may serve as a guide for public health interventions, especially in resource-limited areas.

Long-term change in incidence and risk factors of cirrhosis and hepatocellular carcinoma in Crete, Greece: a 25-year study.

BACKGROUND: No sequential long-term data exist for Greece on the etiological evolution and incidence of cirrhosis and hepatocellular carcinoma. Therefore, we studied their etiological evolution over a period of 25 years in the island of Crete. METHODS: We studied 812 cases of cirrhosis (561 male, median age 69 years) and 321 cases of hepatocellular carcinoma (234 male, median age 70 years) from the database of our Center. Cases were classified into five-year periods according to incidence and etiology (hepatitis B, hepatitis C, alcohol, alcohol plus viral, and non-alcoholic fatty liver disease). RESULTS: Overall, there was an increase in the incidence of hepatocellular carcinoma. A significant fourfold reduction in the incidence of hepatitis C-related cirrhosis was observed, which was degraded from first to third place as a risk factor for cirrhosis. Alcohol gradually became the first risk factor in cirrhosis (1990-94: 36.1%, 2010-14: 52.3%) and carcinoma, while the steepest increase in incidence of cirrhosis and carcinoma was associated with non-alcoholic fatty liver disease. CONCLUSIONS: The incidence of cirrhosis remained constant over the years, but the incidence of hepatocellular carcinoma increased during the last decade. Risk factors for cirrhosis and hepatocellular carcinoma have changed over the past 25 years in Crete. The initial high hepatitis C virus association has significantly decreased, with alcohol now ranking first among risk factors. Non-alcoholic fatty liver disease is continually increasing and is a prominent risk factor for cirrhosis and hepatocellular carcinoma.

Clinical and laboratory characteristics, epidemiology, and outcomes of murine typhus: A systematic review.

Murine or endemic typhus, a febrile disease caused by Rickettsia typhi, is often misdiagnosed due to its non-specific presentation. We sought to evaluate all available evidence in the literature regarding the clinical and laboratory manifestations, epidemiological characteristics, and outcomes of murine typhus. Pubmed was searched for all articles providing available data. In an effort to incorporate contemporary data, only studies from 1980 were included. Thirty-three case series including 2074 patients were included in final analysis. Available evidence suggests that the classic triad of fever, headache and rash is encountered in only one-third of patients. Other frequent symptoms were chills, malaise, myalgia, and anorexia. A tetrad of reported laboratory abnormalities consisting of elevated liver enzymes, lactate dehydrogenase, erythrocyte sedimentation rate and hypoalbuminemia was detected. Complications were observed in one-fourth of patients, reported mortality was extremely low, but untreated patients had notably longer duration of fever. Among epidemiological characteristics, a seasonal distribution with most cases reported during warmer months, was the most prominent finding. Murine typhus in children exhibits several different characteristics, with abdominal pain, diarrhea, and sore throat reported more commonly, higher frequency of anemia, lower frequency of hypoalbuminemia, hematuria and proteinuria and a much lower rate of complications. This systematic review of published evidence provides a thorough description of the clinical and laboratory features of murine typhus and highlights important differences in children.

Clinical characteristics, microbiology and outcomes of external ventricular drainage-associated infections: The importance of active treatment.

Data concerning clinical characteristics, microbiology, treatment and outcomes of external ventricular drainage-associated infections (EVDAI) are limited. All hospitalized patients with EVDAI in a University Hospital between January 2009 and December 2015 were retrospective recorded. Only the first episode per patient was included. An antibiotic was considered "active" when its pharmacokinetic properties were appropriate for EVDAI and the implicated microorganism was in vitro susceptible. During the 7-year study period, 36 EVDAI were identified. Median patient age was 53years and 23 (63.9%) were male. Catheter types were intraventricular (70.6%) and lumbar (29.4%). Median catheterization duration before infection was 14days. Gram-negative bacteria (GNB) predominated (57.9%), followed by gram-positives (36.8%) and fungi (5.3%). Administered antibiotics were considered "active" in 69.4% of empirical and in 86.1% of definitive treatment regimens. In 10 infections, intraventricular/intrathecal (IVT) antibiotics were administered. Eleven patients died (30.6%) during hospitalization. Patients who died had higher rates of EVDAI by GNB (p=0.011) and higher rates of treatment with intravenous colistin (p=0.019 for empirical and p=0.006 for definitive colistin). Compared to EVDAI by other pathogens, patients with EVDAI by GNB had longer catheter-days before infection (p<0.001) and higher mortality (p=0.011). In our study, GNB were a frequent cause of EVDAI, and were related with high rates of inactive treatment and mortality. Intravenous colistin alone is not effective and treatment should include IVT antibiotics and intravenous antibiotics that achieve adequate CSF levels.

Clinical Effectiveness, Safety Profile, and Pharmacokinetics of Daptomycin in Pediatric Patients: A Systematic Review.

Infections by Gram-positive pathogens pose a public health risk, especially due to increasing antibiotic resistance. Daptomycin has efficacy against most clinically important Gram-positive bacteria. Although experience regarding use of daptomycin in adults is increasing, studies on pediatric populations are limited. We aimed to evaluate the efficacy, safety, and pharmacokinetics of daptomycin in pediatric settings. We searched MEDLINE and Clinicaltrials.gov (through April 2016) and included 29 original studies in the final analysis. Available evidence suggests that daptomycin in pediatric patients has a favorable safety and tolerability profile and is an efficacious alternative for treatment of Gram-positive bacteremia, endocarditis, and infections of the skin, soft tissues, joints, and bones, especially when resistant strains are involved. However, future studies need to address several issues to determine the optimal dose and various pharmacokinetic parameters in different pediatric age groups.

Clinical epidemiology, treatment and prognostic factors of extensively drug-resistant Acinetobacter baumannii ventilator-associated pneumonia in critically ill patients.

Limited data exist regarding prognostic factors and optimal antimicrobial treatment of infections caused by extensively drug-resistant Acinetobacter baumannii (XDR-AB). This retrospective cohort study included 93 adult patients who developed ventilator-associated pneumonia (VAP) due to XDR-AB in the ICU of the University Hospital of Heraklion, Greece, from October 2012 to April 2015. XDR-AB isolates were mainly susceptible to colistin (93.5%) and tigecycline (25.8%), whereas 6 (6.5%) were pandrug-resistant. Prior to infection, patients had long durations of mechanical ventilation and hospital stay and multiple exposures to antibiotics. Median Charlson co-morbidity and APACHE II scores were 2 and 17, respectively. Mortality at 28 days of infection onset was high (34.4%) despite high rates of in-vitro-active empirical (81.7%) and definitive (90.3%) treatment. Active colistin-based combination therapy (n = 55) and monotherapy (n = 29) groups had similar 28-day mortality (27.6% vs. 30.9%, respectively) and Kaplan-Meier survival estimates over time. In multivariable Cox regression, advanced age (aHR = 1.05 per year increase, 95% CI 1.02-1.09), rapidly fatal underlying disease (aHR = 2.64, 95% CI 0.98-9.17) and APACHE II score (aHR = 1.06 per unit increase, 95% CI 0.99-1.14) were identified as independent predictors of 28-day mortality, but no difference in mortality hazards between the active colistin-based combination therapy and monotherapy groups was produced (aHR = 0.88, 95% CI 0.35-2.38). These results support the use of colistin as a first-line agent against VAP in settings where XDR-AB is endemic, but oppose the introduction of colistin-based combination therapy as standard treatment.