The COVID-19 pandemic led to unprecedented stress on healthcare systems worldwide, forming settings of concern for increasing antimicrobial resistance. We investigated the impact of SARS-CoV-2 preventive measures against healthcare-associated infections (HAIs) from antibiotic-resistant bacteria in two tertiary-care hospitals. We compared infection rates between March 2019 and February 2020 (pre-intervention period) and March 2020 and February 2021 (COVID-19 intervention period) from drug-resistant ESKAPEE bacteria (methicillin-resistant Staphylococcus aureus; vancomycin-resistant Enterococci; carbapenem-resistant Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species and Escherichia coli). Over 24 months, 586 drug-resistant ESKAPEE HAIs occurred in 439 patients (0.3% of 179,629 inpatients) with a mean age of 63 years, with 43% being treated in intensive care units (ICUs), and having a 45% inpatient mortality rate. Interrupted time series analysis revealed increasing infection rates before the intervention that were sharply interrupted by abrupt drops for most pathogens and henceforth remained stable in the ICUs but progressively increased in ordinary wards. In the ICUs, the pooled infection rate was 44% lower over the intervention period compared to the pre-intervention period (incidence rate ratio (IRR) 0.56, 95%CI 0.41-0.75, p < 0.001). Pooled infection rates in the wards were slightly higher over the COVID-19 period (IRR 1.12, 95%CI 0.87-1.45, p = 0.368). The findings confirmed the ancillary beneficial impact of the enhanced bundle of transmission-based precautions adopted against SARS-CoV-2 in rapidly constraining antimicrobial-resistant HAIs in two Greek hospitals.

Greece opened its points of entry on July 1, 2020, with specific guidelines for travellers arriving by sea, air or land. The aim of this article is to examine the effect of tourism on the long term course of the Coronavirus Disease 2019 (COVID-19) pandemic during the pre-vaccination era (June to December 2020) on the popular Greek island of Crete. To achieve this, a cross-sectional serosurvey, repeated at monthly intervals, was conducted to compare the seroprevalence in Crete with seroprevalence in the mainland of Greece. Crete welcomed nearly 2,000,000 travellers during the 2020 summer season. Left-over serum samples were collected and obtained from public and private laboratories located in Greece, including the island of Crete. These samples were tested for the presence of anti-SARS-CoV-2 IgG antibodies. A total of 55,938 samples were collected, 3,785 of which originated from Crete. In Crete, the seroprevalence ranged between 0% (June 2020) and 2.58% (December 2020), while the corresponding seroprevalence in Greece was 0.19% and 10.75%, respectively. We identified 4.16 times lower seropositivity in Crete (2.58%) in comparison with the mainland of Greece (10.75%) during December 2020. Moreover, the monthly infection fatality rate (IFR) in Crete was calculated at 0.09%, compared with 0.21% in mainland Greece for December 2020. The island of Crete presented more than four times lower seroprevalence than the mainland of Greece, despite being a highly attractive tourist destination. This evidence supports the idea that tourism may not have affected the long term course of the COVID-19 pandemic in Greece. However, due to contradicting results from previous studies, further investigation is needed.

Bacterial antibiotic resistance (AMR) is a significant threat to public health, with the sentinel 'ESKAPEE' pathogens, being of particular concern. A cohort study spanning 5.5 years (2016-2021) was conducted at a provincial general hospital in Crete, Greece, to describe the epidemiology of ESKAPEE-associated bacteraemia regarding levels of AMR and their impact on patient outcomes. In total, 239 bloodstream isolates were examined from 226 patients (0.7% of 32 996 admissions) with a median age of 75 years, 28% of whom had severe comorbidity and 46% with prior stay in ICU. Multidrug resistance (MDR) was lowest for Pseudomonas aeruginosa (30%) and Escherichia coli (33%), and highest among Acinetobacter baumannii (97%); the latter included 8 (22%) with extensive drug-resistance (XDR), half of which were resistant to all antibiotics tested. MDR bacteraemia was more likely to be healthcare-associated than community-onset (RR 1.67, 95% CI 1.04-2.65). Inpatient mortality was 22%, 35% and 63% for non-MDR, MDR and XDR episodes, respectively (P = 0.004). Competing risks survival analysis revealed increasing mortality linked to longer hospitalisation with increasing AMR levels, as well as differential pathogen-specific effects. A. baumannii bacteraemia was the most fatal (14-day death hazard ratio 3.39, 95% CI 1.74-6.63). Differences in microbiology, AMR profile and associated mortality compared to national and international data emphasise the importance of similar investigations of local epidemiology.

BACKGROUND Pneumonia and bloodstream infections (BSI) due to extensively drug-resistant (XDR) Acinetobacter baumannii, XDR Pseudomonas aeruginosa, and carbapenem-resistant Enterobacterales (CRE) are associated with high mortality rates, and therapeutic options remain limited. This trial assessed whether combination therapy with colistin and meropenem was superior to colistin monotherapy for the treatment of these infections. METHODS The OVERCOME (Colistin Monotherapy versus Combination Therapy) trial was an international, randomized, double-blind, placebo-controlled trial. We randomly assigned participants to receive colistin (5 mg/kg once followed by 1.67 mg/kg every 8 hours) in combination with either meropenem (1000 mg every 8 hours) or matching placebo for the treatment of pneumonia and/or BSI caused by XDR A. baumannii, XDR P. aeruginosa, or CRE. The primary outcome was 28-day mortality, and secondary outcomes included clinical failure and microbiologic cure. RESULTS Between 2012 and 2020, a total of 464 participants were randomly assigned to treatment, and 423 eligible patients comprised the modified intention-to-treat population. A. baumannii was the predominant trial pathogen (78%) and pneumonia the most common index infection (70%). Most patients were in the intensive care unit at the time of enrollment (69%). There was no difference in mortality (43 vs. 37%; P=0.17), clinical failure (65 vs. 58%; difference, 6.8 percentage points; 95% confidence interval [CI], -3.1 to 16.6), microbiologic cure (65 vs. 60%; difference, 4.8 percentage points; 95% CI, -5.6 to 15.2), or adverse events (acute kidney injury, 52 vs. 49% [P=0.55]; hypersensitivity reaction, 1 vs. 3% [P=0.22]; and neurotoxicity, 5 vs. 2% [P=0.29]) between patients receiving monotherapy and combination therapy, respectively. CONCLUSIONS Combination therapy with colistin and meropenem was not superior to colistin monotherapy for the treatment of pneumonia or BSI caused by these pathogens. (Funded by the National Institute of Allergy and Infectious Diseases, Division of Microbiology and Infectious Diseases protocol 10-0065; ClinicalTrials.gov number, NCT01597973.).

Hyponatremia is the most common electrolyte disorder, commonly affecting older hospitalized individuals; however, the literature is not clear regarding its effect on mortality. The aim of this 2-year observational prospective cohort study was to evaluate the mortality and re-admission rates, the clinical and laboratory characteristics and the causes of hyponatremia in patients older than 65 years admitted with a corrected serum sodium of 130 mEq/L or less in an internal medicine ward of a tertiary Greek university hospital. During the observation period, 138 patients (mean age 80.5 years, 36.2% male) fulfilled the inclusion criteria and were prospectively followed for 1 year after admission. Symptoms of hyponatremia were present in 59.4% of patients. Hypovolemia was the main sole cause of hyponatremia, but in about one third of patients, hyponatremia was multifactorial. Only a low proportion of patients (12.3%) fulfilled the criteria of the syndrome of inappropriate antidiuresis (SIAD) at admission according to the current guidelines. The re-admission rates at 3- and 12-months following discharge was 34.2% and 51.8%, respectively. Mortality during hospitalization was 17.4% and was higher compared to non-hyponatremic admitted older patients, while the total mortality at 1 year after admission was 28.3%, indicating that hyponatremia at admission is a marker of significant mortality during and after hospitalization in elderly patients.

A Knowledge, Attitudes and Practices (KAP) study was conducted at the end of May 2021 engaging 1456 healthcare workers (HCWs) from 20 hospitals throughout Greece. Acceptance of vaccination against coronavirus disease 2019 (COVID-19) was estimated at 77.7%, with lower vaccine acceptance identified in nurses compared to physicians. Fears related to vaccine safety, lack of information and general knowledge about vaccinations, influenza vaccine acceptance, education level and years of practice were among the factors independently associated with vaccine acceptance. A strong association was identified between vaccination of HCWs in each health region and the population coverage, indicating that HCWs may be role models for the general population. Information campaigns should continue despite decisions taken regarding mandatory vaccinations.

Background: We report the results of INICC surveillance study from 2013 to 2018, in 664 intensive care units (ICUs) in 133 cities, of 45 countries, from Latin-America, Europe, Africa, Eastern-Mediterranean, Southeast-Asia, and Western-Pacific. Methods: Prospective data from patients hospitalized in ICUs were collected through INICC Surveillance Online System. CDC-NHSN definitions for device-associated healthcare-associated infection (DA-HAI) were applied. Results: We collected data from 428,847 patients, for an aggregate of 2,815,402 bed-days, 1,468,216 central line (CL)-days, 1,053,330 mechanical ventilator (MV)-days, 1,740,776 urinary catheter (UC)-days. We found 7,785 CL-associated bloodstream infections (CLAB), 12,085 ventilator-associated events (VAE), and 5,509 UC-associated uri-nary tract infections (CAUTI). Pooled DA-HAI rates were 5.91% and 9.01 DA-HAIs/1,000 bed-days. Pooled CLAB rate was 5.30/1,000 CL-days; VAE rate was 11.47/1,000 MV-days, and CAUTI rate was 3.16/1,000 UC-days. P aeru-ginosa was non-susceptible (NS) to imipenem in 52.72% of cases; to colistin in 10.38%; to ceftazidime in 50%; to ciprofloxacin in 40.28%; and to amikacin in 34.05%. Klebsiella spp was NS to imipenem in 49.16%; to ceftazidime in 78.01%; to ciprofloxacin in 66.26%; and to amikacin in 42.45%. coagulase-negative Staphylococci and S aureus were NS to oxacillin in 91.44% and 56.03%, respectively. Enterococcus spp was NS to vancomycin in 42.31% of the cases. Conclusions: DA-HAI rates and bacterial resistance are high and continuous efforts are needed to reduce them. (c) 2021 Published by Elsevier Inc. on behalf of Association for Professionals in Infection Control and Epidemiology, Inc.

Background: Surveillance is essential to all aspects of management of healthcare-associated infections (HAIs) in critically ill children, where data are limited. We conducted an active surveillance study to elucidate epidemiology, resistance, antimicrobial treatment practices and outcomes of pediatric intensive care unit-acquired HAIs in a southern European country. Methods: Four Greek pediatric intensive care unit encounters (153 patients, 2183 patient-days) during a 6-month period participated using the European Centre for Disease Prevention and Control HAI-net ICU (v2.2) protocol. Bloodstream infections and device-associated HAIs were recorded. Clinical severity, isolated pathogens, antimicrobial resistance and antibiotic prescriptions were collected on a daily basis. Mortality and excess length of stay due to HAI were also assessed. Results: Overall rate of HAIs was 18.3 per 1000 patient-days. Aggregate rates for device-associated HAI were: catheter-related bloodstream infection 2.32, intubation-associated pneumonia 10.5, and catheter-associated urinary tract infection 4.6 per 1000 device-days. Children with HAI (n = 28, 18.3%) had higher severity of illness (Pediatric Risk Mortality Score 7.5 vs. 4, P < 0.001), longer hospitalization (23 vs. 6 days, P < 0.001), but not higher mortality, compared with those without. Most frequent recovered pathogens were Klebsiella pneumoniae (40%), Pseudomonas aeruginosa (22.5%), Acinetobacter baumannii (12.5%), with respective carbapenem resistance 50%, 44% and 80%, and Staphylococcus aureus (12.5%). Total antibiotic use was 2142 days of treatment per 1000 patient-days. Conclusions: Our study, based on the updated ECDC HAI-net ICU (v2.2) protocol, effectively addresses the significant burden of HAIs in critically ill children in Greece. Using a well-standardized system facilitates inter- and intra-countries reliable recordings and comparative assessments of infection control programs.

A serosurvey of IgG antibodies against SARS-CoV-2 was conducted in Greece between May and August 2020. It was designed as a cross-sectional survey and was repeated at monthly intervals. The leftover sampling methodology was used and a geographically stratified sampling plan was applied. Of 20,110 serum samples collected, 89 (0.44%) were found to be positive for anti-SARS-CoV-2 antibodies, with higher seroprevalence (0.35%) observed in May 2020. The highest seroprevalence was primarily observed in the “30–49” year age group. Females presented higher seroprevalence compared to males in May 2020 (females: 0.58% VS males: 0.10%). This difference reversed during the study period and males presented a higher proportion in August 2020 (females: 0.12% VS males: 0.58%). Differences in the rate of seropositivity between urban areas and the rest of the country were also observed during the study period. The four-month infection fatality rate (IFR) was estimated to be 0.47%, while the respective case fatality rate (CFR) was at 1.89%. Our findings confirm low seroprevalence of COVID-19 in Greece during the study period. The young adults are presented as the most affected age group. The loss of the cumulative effect of seropositivity in a proportion of previous SARS-CoV-2 infections was indicated.

Abstract Background Consensus guidelines caution against colistin (COL) monotherapy due to efficacy and resistance development concerns. The COL + meropenem (MEM) combination often displays in vitro synergy against carbapenem-resistant (CR) Gram-negative bacilli (GNB). We recently completed a clinical trial comparing outcomes in patients receiving COL vs. COL + MEM. Herein we assess if, amongst patients receiving COL + MEM, outcomes differed as a function of the presence (or absence) of in vitro synergy against the index pathogen. Methods OVERCOME was an international, multicenter, randomized, double-blind, placebo-controlled study comparing COL + placebo and COL + MEM for the treatment of pneumonia and/or bloodstream infection (BSI) due to CR GNB. Baseline isolates were COL susceptible (MIC ≤ 2 mg/L) and underwent synergy testing to COL + MEM in 24-hour time kill experiments (TKE). Synergy was defined as a >2-log CFU/ml reduction with combination therapy compared to the most active single agent. Outcomes assessed included 28-day mortality, clinical failure, and the development of COL resistance (MIC ≥ 4 mg/L) for both the overall cohort and the subgroup with A. baumannii. Results Of the 211 patients who received COL + MEM in OVERCOME, 186 had baseline synergy testing performed and were eligible for this analysis. The median age of the cohort was 70 years, 35% were female, 48% were white, and 44% Asian. Sixty-eight percent were in the intensive care unit (ICU) at infection onset. A. baumannii was the most common pathogen (78%) and pneumonia was the most common infection (68%). Synergy was demonstrated in most isolates (76%). Baseline characteristics, clinical, and microbiological outcomes were similar amongst patients infected with isolates against which COL + MEM demonstrated synergy and those where no synergy was demonstrated (Table 1). In patients with A. baumannii infections, the presence of in vitro synergy was associated with a decrease in clinical failure (53% vs. 79%; p = 0.04). No significant impact of synergy on 28-day mortality or development of COL resistance was demonstrated (Table 2). Conclusion The presence of in vitro synergy via TKE was associated with a decrease in clinical failure in patients treated with COL + MEM for invasive infections due to CR A. baumannii. Disclosures Jason M Pogue, PharmD, BCPS, BCIDP, Merck (Consultant)QPex (Consultant)Shionogi (Consultant)Utility Therapeutics (Consultant)VenatoRX (Consultant) Michael J. Rybak, PharmD, MPH, PhD, Paratek Pharmaceuticals (Research Grant or Support) Emmanuel Roilides, MD, PhD, FIDSA, FAAM, FESCMID, Merck Sharp & Dohme Corp. (Consultant, Grant/Research Support) Matthew Sims, MD, PhD, Astra Zeneca (Independent Contractor)Diasorin Molecular (Independent Contractor)Epigenomics Inc (Independent Contractor)Finch (Independent Contractor)Genentech (Independent Contractor)Janssen Pharmaceuticals NV (Independent Contractor)Kinevant Sciences gmBH (Independent Contractor)Leonard-Meron Biosciences (Independent Contractor)Merck and Co (Independent Contractor)OpGen (Independent Contractor)Prenosis (Independent Contractor)Regeneron Pharmaceuticals Inc (Independent Contractor)Seres Therapeutics Inc (Independent Contractor)Shire (Independent Contractor)Summit Therapeutics (Independent Contractor)

Abstract Background Colistin (COL) remains an important therapeutic option for carbapenem-resistant (CR) Gram-negative bacilli (GNB). COL is often utilized in combination with meropenem (MEM), in part due to concerns regarding the development of COL resistance with monotherapy. We recently completed a randomized controlled trial comparing outcomes in patients receiving COL + placebo to those receiving COL + MEM; herein we present data on the emergence of COL resistance in this trial. Methods OVERCOME was an international, multicenter, randomized, double-blind, placebo-controlled study comparing COL and COL + MEM for the treatment of bloodstream infection and/or pneumonia due to CR GNB. Subjects were included in the modified intent to treat population (mITT) if their enrollment pathogen had a COL MIC ≤2 mg/L, as determined by broth microdilution (BMD). Daily blood and/or respiratory samples were obtained in patients per protocol until two consecutive negatives were obtained or the end of study treatment. All subsequent isolates were evaluated for COL resistance via BMD, defined as MIC ≥ 4 mg/L. Results Of the 425 patients in the mITT population, 380 (191 COL; 189 COL + MEM) were evaluable for the endpoint of COL resistance development. The median age of the cohort was 70, 38% were female, 47% were white, and 45% were Asian. 70% had an index infection of pneumonia, 68% were in the intensive care unit at the onset of their infection, and A. baumannii was the most common pathogen (78% of patients). Baseline characteristics, infection type, severity of illness, and index pathogen were similar amongst treatment arms. No significant difference in resistance development was seen between the COL and COL + MEM groups overall (12% vs. 8%; p = 0.31), or in any subgroup (Table). In patients with A. baumannii, there was a trend towards decreased resistance development with COL + MEM (13.3% vs 7.5%; p = 0.13). Conclusion We were unable to identify a significant difference in resistance emergence between treatment arms, but given the low incidence of this outcome, were underpowered to do so. The impact of COL + MEM on preventing emergence of COL resistance in A. baumannii warrants further clinical study. Disclosures Jason M Pogue, PharmD, BCPS, BCIDP, Merck (Consultant)QPex (Consultant)Shionogi (Consultant)Utility Therapeutics (Consultant)VenatoRX (Consultant) Michael J. Rybak, PharmD, MPH, PhD, Paratek Pharmaceuticals (Research Grant or Support) Emmanuel Roilides, MD, PhD, FIDSA, FAAM, FESCMID, Merck Sharp & Dohme Corp. (Consultant, Grant/Research Support) Matthew Sims, MD, PhD, Astra Zeneca (Independent Contractor)Diasorin Molecular (Independent Contractor)Epigenomics Inc (Independent Contractor)Finch (Independent Contractor)Genentech (Independent Contractor)Janssen Pharmaceuticals NV (Independent Contractor)Kinevant Sciences gmBH (Independent Contractor)Leonard-Meron Biosciences (Independent Contractor)Merck and Co (Independent Contractor)OpGen (Independent Contractor)Prenosis (Independent Contractor)Regeneron Pharmaceuticals Inc (Independent Contractor)Seres Therapeutics Inc (Independent Contractor)Shire (Independent Contractor)Summit Therapeutics (Independent Contractor)

Pandrug-resistant A. baumannii (PDRAB) is increasingly being reported but remains rare. Several case studies show that A. baumannii can acquire resistance to last resort antibiotics during treatment by single-step chromosomal mutations. However, re-emergence of the ancestral susceptible strain after withdrawal of antibiotics has been described, possibly due to fitness cost associated with acquired resistance. Therefore, PDRAB may be a transient phenotype. Epidemiological data to show this process in larger cohorts are currently lacking. In this study of 91 hospitalized patients with PDRAB we showed the frequent (60%) isolation of non-PDRAB, often susceptible only to colistin, aminoglycosides and/or tigecycline, preceding and/or following PDRAB isolation. However, the isolation of PDRAB in two outpatients, 25 and 36 days after their discharge from the hospital, suggests the potential of some PDRAB strains to persist even in the absence of antimicrobial pressure.

Concern exists in Europe about the possibility of importation of infectious diseases due to the recent influx of migrants and refugees after 2011. In this retrospective 6-year study, we examined the epidemiology of fever of unknown origin (FUO) in Greece over the past years. Forty-eight patients with classical FUO were included. The proportion of infectious causes of FUO (29.2%) was similar to previous studies in Greece and all infections were endemic to the area. Disease-related mortality was 12.5% and no deaths due to infection were recorded. In conclusion, none of the diagnosed infectious causes of FUO raised concerns about the possibility of imported diseases or pathogens. These results re-inforce the perception that migrants and refugees are not carriers of communicable diseases that can cause public health problems to European countries.

Background The literature on the epidemiology, mortality and treatment of pandrug-resistant (PDR) Gram-negative bacteria (GNB) is scarce, scattered and controversial. Objectives To consolidate the relevant literature and identify treatment options for PDR GNB infections. Methods A systematic search in MEDLINE, Scopus and clinical trial registries was conducted. Studies reporting PDR clinical isolates were eligible for review if susceptibility testing for all major antimicrobials had been performed. Characteristics and findings of retrieved studies were qualitatively synthesized. Results Of 81 studies reviewed, 47 (58%) were published in the last 5years. The reports reflected a worldwide dissemination of PDR GNB in 25 countries in 5 continents. Of 526 PDR isolates reported, Pseudomonas aeruginosa (n=175), Acinetobacter baumannii (n=172) and Klebsiella pneumoniae (n=125) were most common. PDR GNB were typically isolated in ICUs, but several studies demonstrated wider outbreak potential, including dissemination to long-term care facilities and international spread. All-cause mortality was high (range 20%-71%), but appeared to be substantially reduced in studies reporting treatment regimens active in vitro. No controlled trial has been performed to date, but several case reports and series noted successful use of various regimens, predominantly synergistic combinations, and in selected patients increased exposure regimens and newer antibiotics. Conclusions PDR GNB are increasingly being reported worldwide and are associated with high mortality. Several treatment regimens have been successfully used, of which synergistic combinations appear to be most promising and often the only available option. More pharmacokinetic/pharmacodynamic and outcome studies are needed to guide the use of synergistic combinations.

Murine typhus, a flea-borne infectious disease caused by Rickettsia typhi, occurs in environments where rats and humans live in close proximity and typically in temperate and sub-tropical seaboard regions during warm seasons. R. typhi usually causes a mild form of illness, but severe forms of the disease can also occur. Clinical manifestations, which are non-specific, usually include fever, headache, malaise, and rash. The disease can be complicated with renal, pulmonary, central nervous system involvement, and ultimately multi-organ failure. Clinical suspicion is necessary for diagnosis of acute infection, as antibodies may not be detectable until late illness or convalescence. Although serology confirms the diagnosis, detection of rickettsial DNA by polymerase chain reaction in blood or skin samples or rickettsial antigen by immunohistochemistry serve as a reliable assay for early diagnosis. Doxycycline or—when contraindicated—an alternative such as chloramphenicol is considered effective to treat patients with murine typhus.

Background: Pandrug-resistant Acinetobacter baumannii (PDRAB) is increasingly being reported as a nosocomial pathogen worldwide, but determining its clinical impact is challenging. Aim: To assess the spectrum of excess mortality attributable to PDRAB infection in acute care settings. Methods: This four-year cohort study was conducted in a tertiary-care referral hospital in Greece to estimate excess in-hospital mortality due to PDRAB infection by comparing patients infected to those colonized with PDRAB by means of competing risks survival analysis. Findings: The study cohort comprised 91 patients (median age: 67 years; 77% men). For most patients, PDRAB was first isolated in the intensive care unit (ICU) (N = 51; 57%) or following ICU discharge (N = 26; 29%). Overall in-hospital mortality was 68% (95% confidence interval (CI): 57.5-77.5%). PDRAB-infected patients (N = 62; 68%) and PDRAB-colonized patients (N = 29; 32%) had similar baseline characteristics, but the absolute excess risk of 30-day mortality in infected patients compared to colonized patients was 34% (95% CI: 14-54%). Multivariable competing risks regression showed that PDRAB infection significantly increased the daily hazard of 30-day in-hospital death (cause-specific hazard ratio (csHR): 3.10; 95% CI: 1.33-7.21) while simultaneously decreasing the daily rate of discharge (csHR: 0.24; 95% CI: 0.08-0.74), thereby leading to longer hospitalization. Stronger effects were observed for bloodstream infections. Conclusion: New effective antimicrobials would be expected to prevent mortality in one of every three patients treated for PDRAB infection and reduce their length of hospitalization. However, available therapeutic options remain extremely limited and emphasis on preventing healthcare-associated transmission of PDRAB is ever more important. (C) 2020 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

The management of carbapenem-resistant infections is often based on polymyxins, tigecycline, aminoglycosides and their combinations. However, in a recent systematic review, we found that Gram-negative bacteria (GNB) co-resistant to carbapanems, aminoglycosides, polymyxins and tigecycline (CAPT-resistant) are increasingly being reported worldwide. Clinical data to guide the treatment of CAPT-resistant GNB are scarce and based exclusively on few case reports and small case series, but seem to indicate that appropriate (in vitro active) antimicrobial regimens, including newer antibiotics and synergistic combinations, may be associated with lower mortality. In this review, we consolidate the available literature to inform clinicians dealing with CAPT-resistant GNB about treatment options by considering the mechanisms of resistance to carbapenems. In combination with rapid diagnostic methods that allow fast detection of carbapenemase production, the approach proposed in this review may guide a timely and targeted treatment of patients with infections by CAPT-resistant GNB. Specifically, we focus on the three most problematic species, namely Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii. Several treatment options are currently available for CAPT-resistant K. pneumonia. Newer β-lactam-β-lactamase combinations, including the combination of ceftazidime/avibactam with aztreonam against metallo-β-lactamase-producing isolates, appear to be more effective compared to combinations of older agents. Options for P. aeruginosa (especially metallo-β-lactamase-producing strains) and A. baumannii remain limited. Synergistic combination of older agents (e.g., polymyxin- or fosfomycin-based synergistic combinations) may represent a last resort option, but their use against CAPT-resistant GNB requires further study.

Background: We report the results of International Nosocomial Infection Control Consortium (INICC) surveillance study from January 2012 to December 2017 in 523 intensive care units (ICUs) in 45 countries from Latin America, Europe, Eastern Mediterranean, Southeast Asia, and Western Pacific. Methods: During the 6-year study period, prospective data from 532,483 ICU patients hospitalized in 242 hospitals, for an aggregate of 2,197,304 patient days, were collected through the INICC Surveillance Online System (ISOS). The Centers for Disease Control and Prevention-National Healthcare Safety Network (CDC-NHSN) definitions for device-associated health care-associated infection (DA-HAI) were applied. Results: Although device use in INICC ICUs was similar to that reported from CDC-NHSN ICUs, DA-HAI rates were higher in the INICC ICUs: in the medical-surgical ICUs, the pooled central line-associated bloodstream infection rate was higher (5.05 vs 0.8 per 1,000 central line-days); the ventilator-associated pneumonia rate was also higher (14.1 vs 0.9 per 1,000 ventilator-days,), as well as the rate of catheter-associated urinary tract infection (5.1 vs 1.7 per 1,000 catheter-days). From blood cultures samples, frequencies of resistance, such as of Pseudomonas aeruginosa to piperacillin-tazobactam (33.0% vs 18.3%), were also higher. Conclusions: Despite a significant trend toward the reduction in INICC ICUs, DA-HAI rates are still much higher compared with CDC-NHSN's ICUs representing the developed world. It is INICC's main goal to provide basic and cost-effective resources, through the INICC Surveillance Online System to tackle the burden of DA-HAIs effectively. (C) 2019 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Background Infections with multidrug resistant (MDR) bacteria in hospital settings have substantial implications in terms of clinical and economic outcomes. However, due to clinical and methodological heterogeneity, estimates about the attributable economic and clinical effects of healthcare-associated infections (HAI) due to MDR microorganisms (MDR HAI) remain unclear. The objective was to review and synthesize the evidence on the impact of MDR HAI in adults on hospital costs, length of stay, and mortality at discharge. Methods and findings Literature searches were conducted in PubMed/MEDLINE, and Google Scholar databases to select studies that evaluated the impact of MDR HAI on economic and clinical outcomes. Eligible studies were conducted in adults, in order to ensure homogeneity of populations, used propensity score matched cohorts or included explicit confounding control, and had confirmed antibiotic susceptibility testing. Risk of bias was evaluated, and effects were measured with ratios of means (ROM) for cost and length of stay, and risk ratios (RR) for mortality. A systematic search was performed on 14th March 2019, re-run on the 10th of June 2019 and extended the 3rd of September 2019. Small effect sizes were assessed by examination of funnel plots. Sixteen articles (6,122 patients with MDR HAI and 8,326 patients with non-MDR HAI) were included in the systematic review of which 12 articles assessed cost, 19 articles length of stay, and 14 mortality. Compared to susceptible infections, MDR HAI were associated with increased cost (ROM 1.33, 95%CI [1.15; 1.54]), prolonged length of stay (ROM 1.27, 95%CI [1.18; 1.37]), and excess in-hospital mortality (RR 1.61, 95%CI [1.36; 1.90]) in the random effects models. Risk of publication bias was only found to be significant for mortality, and overall study quality good. Conclusions MDR HAI appears to be strongly associated with increases in direct cost, prolonged length of stay and increased mortality. However, further comprehensive studies in this setting are warranted. Trial registration PROSPERO (CRD42019126288).