Antimicrobial prescribing before and after the implementation of a carbapenem-focused antimicrobial stewardship program in a Greek tertiary hospital during the COVID-19 pandemic

Background: Irrational use of antimicrobials poses a significant risk for public health by aggravating antimicrobial resistance. The aim of this repeated point prevalence survey (PPS) was to evaluate the impact of a carbapenem-focused antimicrobial stewardship program (ASP) on overall antimicrobial use and quality of antimicrobial prescribing during the COVID-19 pandemic. Methods: All adult inpatients in the University Hospital of Heraklion in Greece were audited twice, before and after the implementation of the ASP, in October 2019 and October 2020, respectively. Patient characteristics, indications and diagnoses for antimicrobial administration, antimicrobials prescribed, and compliance with treatment guidelines were recorded. Results: Of 743 adult inpatients on the days of the two surveys, 398 (53.6%) were on antimicrobials for 437 diagnoses. Following implementation of the ASP, there was substantial decrease in the utilization of carbapenems (4.9% of all antibacterials prescribed in the second PPS compared to 10.3% in the first PPS). A significant improvement was observed for all indicators of the quality of antimicrobial prescribing. Conclusions: Our study demonstrated a positive impact of an ASP implementation during the first stages of the COVID-19 pandemic on reducing the use of last-line antimicrobials and improving overall quality of antimicrobial prescribing

Impact of SARS-CoV-2 preventive measures against healthcare-associated infections from antibiotic-resistant ESKAPEE pathogens: a two-center, natural quasi-experimental study in Greece

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

Indications for medical antibiotic prophylaxis and potential targets for antimicrobial stewardship intervention: a narrative review

BACKGROUND: Most of the antimicrobial stewardship (AMS) literature has focused on antimicrobial consumption for the treatment of infections, for the prophylaxis of surgical site infection and for the prevention of endocarditis. The role of AMS for medical antibiotic prophylaxis (AP) has not been adequately addressed. AIMS: To identify targets for AMS interventions for medical AP in adult patients. SOURCES: Targeted searches were conducted in PubMed. CONTENT: The various indications for medical AP and relevant evidence from practice guidelines are outlined. The following were identified as potential targets for AMS interventions: (a) addressing under-utilization of antibiotic-sparing strategies (e.g. for recurrent urinary tract infections, recurrent soft-tissue infections, recurrent exacerbations associated with bronchiectasis or chronic obstructive pulmonary disease), (b) reducing unnecessary AP beyond recommended indications (e.g. for acute pancreatitis, bite wounds, or urinary catheter manipulations), (c) reducing the use of AP with a broader spectrum than necessary, (d) reducing the use of AP for longer than the recommended duration (e.g. AP for prevention of osteomyelitis in open fractures or AP in high-risk neutropenia), (e) evaluating the role of antibiotic cycling to prevent the emergence of resistance during prolonged AP (e.g. in recurrent urinary tract infections or prophylaxis for spontaneous bacterial peritonitis), and (f) addressing research gaps regarding appropriate indications or antibiotic regimens for medical prophylaxis. IMPLICATIONS: This review summarizes current trends in AP and proposes targets for AMS interventions. BACKGROUND: The effect of fluid management strategies in critical illness-associated diaphragm weakness are unknown. This study hypothesized that a liberal fluid strategy induces diaphragm muscle fiber edema, leading to reduction in diaphragmatic force generation in the early phase of experimental pediatric acute respiratory distress syndrome in lambs. METHODS: Nineteen mechanically ventilated female lambs (2 to 6 weeks old) with experimental pediatric acute respiratory distress syndrome were randomized to either a strict restrictive fluid strategy with norepinephrine or a liberal fluid strategy. The fluid strategies were maintained throughout a 6-h period of mechanical ventilation. Transdiaphragmatic pressure was measured under different levels of positive end-expiratory pressure (between 5 and 20 cm H2O). Furthermore, diaphragmatic microcirculation, histology, inflammation, and oxidative stress were studied. RESULTS: Transdiaphragmatic pressures decreased more in the restrictive group (-9.6 cm H2O [95% CI, -14.4 to -4.8]) compared to the liberal group (-0.8 cm H2O [95% CI, -5.8 to 4.3]) during the application of 5 cm H2O positive end-expiratory pressure (P = 0.016) and during the application of 10 cm H2O positive end-expiratory pressure (-10.3 cm H2O [95% CI, -15.2 to -5.4] vs. -2.8 cm H2O [95% CI, -8.0 to 2.3]; P = 0.041). In addition, diaphragmatic microvessel density was decreased in the restrictive group compared to the liberal group (34.0 crossings [25th to 75th percentile, 22.0 to 42.0] vs. 46.0 [25th to 75th percentile, 43.5 to 54.0]; P = 0.015). The application of positive end-expiratory pressure itself decreased the diaphragmatic force generation in a dose-related way; increasing positive end-expiratory pressure from 5 to 20 cm H2O reduced transdiaphragmatic pressures with 27.3% (17.3 cm H2O [95% CI, 14.0 to 20.5] at positive end-expiratory pressure 5 cm H2O vs. 12.6 cm H2O [95% CI, 9.2 to 15.9] at positive end-expiratory pressure 20 cm H2O; P < 0.0001). The diaphragmatic histology, markers for inflammation, and oxidative stress were similar between the groups. CONCLUSIONS: Early fluid restriction decreases the force-generating capacity of the diaphragm and diaphragmatic microcirculation in the acute phase of pediatric acute respiratory distress syndrome. In addition, the application of positive end-expiratory pressure decreases the force-generating capacity of the diaphragm in a dose-related way. These observations provide new insights into the mechanisms of critical illness-associated diaphragm weakness. BACKGROUND: COVID19 is a viral disease with pneumonia as its most common presentation. Many presentations and complications have been reported, but gastro-intestinal perforation has not received much attention. METHODS: three cases from our hospital are presented, and the current literature was reviewed. RESULTS, CASES: All three patients were admitted to the ICU with respiratory failure due to COVID19 pneumonia and intubated. Our first patient was treated with steroids, and subsequently diagnosed with rectal perforation on day 34 of his hospital admission. The second patient was treated with steroids and tocilizumab, and diagnosed with colonic perforation 1 day after neostigmine administration, on day 14 of his hospital admission. Our third patient was treated with steroids and tocilizumab, and diagnosed colonic perforation 4 days after neostigmine administration, on day 14 of his hospital admission. RESULTS, LITERATURE: 25 more cases were found in current literature, both upper GI and lower GI perforations, either as a presenting symptom or during the course of hospitalization. These were often associated with treatment with steroids, interleukin 6 inhibitors, or both. CONCLUSIONS: Gastro-intestinal perforation is a rare but dangerous complication of COVID19. Treatment with tocilizumab and steroids may both increase the risk of this complication, and hamper diagnosis

Management of invasive fungal infections in adult patients with hematological malignancies in Greece during the financial crisis: Challenges and recommendations

There are concerns that the financial crisis in Greece negatively affected the management of invasive fungal infections (IFIs) among patients with hematological malignancies (HM). A working group (WG) was formed to explore the situation and make recommendations. A questionnaire was created and distributed to physicians caring for patients with HM, to gather information in a standardized manner on prescribing physicians, patient characteristics, availability of diagnostics, antifungal treatment practices and the conditions and particularities of Greek hospitals. A total of 141 physicians from 36 hematology units and laboratories located in 26 Greek hospitals participated. Regarding hospitalization conditions, only 56% reported that their patients were treated in isolated single or double bed rooms, 22% reported availability of HEPA filters, 47% reported construction works in progress, and an alarming 18% reported the presence of birds on open windows. Regarding diagnosis, only 31% reported availability of biomarkers for diagnosis of IFIs, 76% reported that CT scans were performed in a timely fashion, 42% reported prompt availability of broncho-alveolar lavage, and only 6% availability of therapeutic drug monitoring. Of concern, 26% of the responders reported non-availability of some antifungals. In conclusion, significant challenges exist for the optimal management of IFIs in patients with HM in Greece. © 2018 by the authors. Licensee MDPI, Basel, Switzerland

A carbapenem-focused antimicrobial stewardship programme implemented during the COVID-19 pandemic in a setting of high endemicity for multidrug-resistant Gram-negative bacteria

Background Greece is among the countries characterized by high rates of antimicrobial resistance and high consumption of antibiotics, including carbapenems. Objectives To measure the impact of a carbapenem-focused antimicrobial stewardship programme (ASP) on the antibiotic consumption and patient outcomes in a Greek tertiary hospital during the COVID-19 pandemic. Methods A quasi-experimental, before–after study, comparing a 12 month pre-intervention period with a 12 month intervention period in which a carbapenem-focused ASP was implemented. Results A total of 1268 patients were enrolled. The proportion of admitted patients who received carbapenems decreased from 4.1% (842 of 20 629) to 2.3% (426 of 18 245) (−1.8%; P < 0.001). A decrease of −4.9 DDD/100 patient-days (PD) (95% CI −7.3 to −2.6; P = 0.007) in carbapenem use and an increase in the use of piperacillin/tazobactam [+2.1 DDD/100 PD (95% CI 1.0–3.3; P = 0.010)] were observed. Thirty-day mortality following initiation of carbapenem treatment and all-cause in-hospital mortality remained unaltered after ASP implementation. In contrast, length of hospital stay increased (median 17.0 versus 19.0 days; P < 0.001), while the risk of infection-related readmission within 30 days of hospital discharge decreased (24.6% versus 16.8%; P = 0.007). In the post-implementation period, acceptance of the ASP intervention was associated with lower daily hazard of in-hospital death [cause-specific HR (csHR) 0.49; 95% CI 0.30–0.80], lower odds of 30 day mortality (OR 0.36; 95% CI 0.18–0.70) and higher rate of treatment success (csHR 2.45; 95% CI 1.59–3.77). Conclusions Implementing and maintaining a carbapenem-focused ASP is feasible, effective and safe in settings with high rates of antimicrobial resistance, even during the COVID-19 pandemic

SARS-CoV-2 pathophysiology and its clinical implications: An integrative overview of the pharmacotherapeutic management of COVID-19

Common manifestations of COVID-19 are respiratory and can extend from mild symptoms to severe acute respiratory distress. The severity of the illness can also extend from mild disease to life-threatening acute respiratory distress syndrome (ARDS). SARS-CoV-2 infection can also affect the gastrointestinal tract, liver and pancreatic functions, leading to gastrointestinal symptoms. Moreover, SARS-CoV-2 can cause central and peripheral neurological manifestations, affect the cardiovascular system and promote renal dysfunction. Epidemiological data have indicated that cancer patients are at a higher risk of contracting the SARS-CoV-2 virus. Considering the multitude of clinical symptoms of COVID-19, the objective of the present review was to summarize their pathophysiology in previously healthy patients, as well as in those with comorbidities. The present review summarizes the current, though admittedly fluid knowledge on the pathophysiology and symptoms of COVID-19 infection. Although unclear issues still remain, the present study contributes to a more complete understanding of the disease, and may drive the direction of new research. The recognition of the severity of the clinical symptoms of COVID-19 is crucial for the specific therapeutic management of affected patients. © 2020 Elsevier Lt