Carbapenem-Resistant Pseudomonas aeruginosa Bacteremia, through a Six-Year Infection Control Program in a Hospital.

BACKGROUND: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a life-threatening healthcare-associated infection affecting especially patients with immunosuppression and comorbidities. We investigated the association between the incidence of CRPA bacteremia, antibiotic consumption, and infection control measures in a hospital during 2013-2018. METHODS: We prospectively recorded the incidence of CRPA bacteremia, antibiotic consumption, use of hand-hygiene solutions, and isolation rates of multidrug-resistant (MDR) carrier patients. FINDINGS: The consumption of colistin, aminoglycosides, and third-generation cephalosporins decreased significantly in the total hospital and its divisions (p-value < 0.001 for all comparisons) while the consumption of carbapenems decreased significantly in the adults ICU (p-value = 0.025). In addition, the incidence of CRPA significantly decreased in the total hospital clinics and departments (p-values = 0.027 and 0.042, respectively) and in adults clinics and departments (p-values = 0.031 and 0.051, respectively), while in the adults ICU, the incidence remained unchanged. Increased isolation rates of MDR carrier patients, even two months before, significantly correlated with decreased incidence of CRPA bacteremia (IRR: 0.20, 95% CI: 0.05-0.73, p-value = 0.015) in the adults ICU. Interestingly, when the use of hand-hygiene solutions (alcohol and/or scrub) increased, the consumption of advanced, nonadvanced, and all antibiotics decreased significantly. CONCLUSION: In our hospital, multimodal infection control interventions resulted in a significant reduction of CRPA bacteremia, mostly due to the reduction of all classes of antibiotics.

Six-Year Time-Series Data on Multidrug-Resistant Bacteremia, Antibiotic Consumption, and Infection Control Interventions in a Hospital.

Background: Multidrug-resistant (MDR) bacteremia is a serious health care-associated infection with significant morbidity and excess hospitalization costs. Our aim is to study the association between incidences of MDR bacteremia, antibiotic consumption, and infection control measures in a hospital from 2013 to 2018. Methods: We analyzed the following indices: (1) incidence of bacteremia (carbapenem-resistant Acinetobacter baumanii, Pseudomonas aeruginosa, and Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococci); (2) use of antibiotics; (3) consumption of disinfectant solutions for hand hygiene; and (4) isolation rates of MDR carrier patients. Findings: The use of advanced antibiotics (p = 0.001) and carbapenems (p = 0.008) decreased significantly in all hospital departments but the incidence of total MDR bacteremia did not change significantly. Increased use of hand disinfectant solutions was statistically associated with decreased incidence of total MDR bacteremia (incidence rate ratio [IRR]: 0.94, confidence interval [95% CI]: 0.90-0.99, p: 0.020) in all hospital. Also, increased isolation rates of MDR carrier patients 2 months before correlated with decreased incidence of bacteremia due to carbapenem-resistant gram-negative pathogens (IRR: 0.35, 95% CI: 0.18-0.66, p: 0.001) in adults intensive care unit. Conclusion: In our hospital, hand hygiene and isolation of MDR carrier patients controlled MDR bacteremia.

Isolated splenic cystic echinococcosis and albendazole hepatotoxicity.

Isolated splenic cystic echinococcosis is a rare condition. In Greece the number of cases has declined substantially in the last 20 years. The spleen is the second most common extrahepatic site of cystic echinococcosis. Albendazole is safe, but mebendazole can be used as a substitute, in case of adverse reaction. Our patient was diagnosed with isolated splenic echinococcal cyst, during the investigation for newly diagnosed type 2 diabetes mellitus. We opted for elective splenectomy, based on a risk assessment due to the patient's working conditions, and treatment with albendazole represented a safety measure until surgery was possible. The patient developed acute hepatocellular injury to albendazole after eight weeks of treatment. This was confirmed through rechallenge with albendazole after discontinuation of the drug. Postsplenectomy the treatment with mebendazole proved to be safe with no adverse reactions. Even though, albendazole is known to be safe, monitoring of hepatic enzymes and full blood count should be offered. In case of toxicities, mebendazole with or without praziquantel can be used. Toxicity to mebendazole can be similar to albendazole but a trial is worthwhile. In our patient, treatment with mebendazole was uneventful.

Association between consumption of antibiotics, infection control interventions and Clostridioides difficile infections: Analysis of six-year time-series data in a tertiary-care hospital in Greece.

BACKGROUND: To investigate the association between Clostridioides difficile infection (CDI), antibiotic use, and infection control interventions, during an antibiotic stewardship program (ASP) implemented in a tertiary-care hospital in Greece from 2013 to 2018. METHODS: Analysis was applied for the following monthly indices: 1. consumption of antibiotics; 2. use of hand hygiene disinfectant solutions; 3. percentage of isolations of patients either with multidrug-resistant (MDR) bacteria, or CDI, or admitted from another hospital; and 4. percentage of patients with CDI divided into two groups: community-acquired CDI (CACDI) and hospital-associated CDI (HACDI) (onset ≤72 h and >72 h after admission, respectively). RESULTS: During the study, a significant reduction in CACDI rate from 0.3%/admissions [95% CI 0.1-0.6] to 0.1%/admissions [95% CI 0.0-0.3] (p-value = 0.035) was observed in adults ICU, while CDI rates were stable in the rest of the hospital. Antibiotic consumption showed a significant reduction in total hospital, from 91.7 DDDs [95% CI 89.7-93.7] to 80.1 DDDs [95% CI 79.1-81.1] (p-value<0.001), except adults ICU. Non-advanced antibiotics correlated with decreased CDI rates in Adults Clinic Departments and ICU. Isolation of patients one and two months earlier correlated with decreased CACDI rates per 20% [95% CI 0.64-1.00, p-value = 0.046] and HACDI per 23% [95% CI 0.60-1.00, p-value = 0.050] in Adults Clinic Departments. Consumption of disinfectant solutions current month correlated with decreased rate for CACDI per 33% [95% CI 0.49-0.91, p-value = 0.011] and HACDI per 38% [95% CI 0.40-0.98, p-value = 0.040] in total Hospital Clinics. CONCLUSION: Rational antibiotic prescribing during ASP along with multipronged intervention strategy focusing on hand hygiene and patient isolation measures prevent and control CDI outbreaks in the hospital setting.

Evolution of epidemiological characteristics of infective endocarditis in Greece.

OBJECTIVE: The clinical profile, management and outcome of infective endocarditis (IE) may be influenced by socioeconomic issues. METHODS: A nationwide prospective study evaluated IE during the era of deep economic crisis in Greece. Epidemiological data and factors associated with 60-day mortality were analyzed through descriptive statistics, logistic and Cox-regression models. RESULTS: Among 224 patients (male 72.3%, mean age 62.4 years), Staphylococcus aureus (n = 62; methicillin-resistant S. aureus (MRSA) 33.8%) predominated in the young without impact on mortality (p = 0.593), whilst Enterococci (n = 36) predominated in the elderly. Complications of IE were associated with mortality: heart failure [OR 2.415 (95% CI: 1.159-5.029), p = 0.019], stroke [OR 3.206 (95% CI: 1.190-8.632), p = 0.018] and acute kidney injury [OR 2.283 (95% CI: 1.085-4.805), p = 0.029]. A 60-day survival benefit was solely related to cardiac surgery for IE during hospitalization [HR 0.386 (95% CI: 0.165-0.903), p = 0.028] and compliance with antimicrobial treatment guidelines [HR 0.487 (95% CI: 0.259-0.916), p = 0.026]. Compared with a previous country cohort study, history of rheumatic fever and native valve predisposition had declined, whilst underlying renal disease and right-sided IE had increased (p < 0.0001); HIV infection had emerged (p = 0.002). No difference in rates of surgery and outcome was assessed. CONCLUSIONS: A country-wide survey of IE highlighted emergence of HIV, right-sided IE and predominance of MRSA in the youth during a severe socioeconomic crisis. Compliance with treatment guidelines promoted survival.

Pharmacokinetics and safety of fidaxomicin in patients with inflammatory bowel disease and Clostridium difficile infection: an open-label Phase IIIb/IV study (PROFILE).

Objectives: Inflammatory bowel disease (IBD) poses an increased risk for Clostridium difficile infection (CDI). Fidaxomicin has demonstrated non-inferiority to vancomycin for initial clinical cure of CDI in patients without IBD; however, lack of data has caused concerns regarding potential systemic absorption of fidaxomicin in patients with IBD. Methods: The plasma pharmacokinetics (PK) of fidaxomicin and its primary metabolite OP-1118 were evaluated in a multicentre, open-label, single-arm, Phase IIIb/IV study enrolling patients with active IBD and CDI. Patients received fidaxomicin, 200 mg twice daily for 10 days. The primary and secondary endpoints were, respectively, plasma and stool PK of fidaxomicin and OP-1118 on Days 1, 5 and 10 of treatment. Other secondary endpoints included safety of fidaxomicin treatment (assessed until Day 180). ClinicalTrials.gov identifier: NCT02437591. Results: Median Tmax of fidaxomicin and OP-1118 for the PK analysis set (PKAS; 24 patients) was 1-2 h across Days 1, 5 and 10. Cmax ranges were 1.2-154 ng/mL for fidaxomicin and 4.7-555 ng/mL for OP-1118 across Days 1, 5 and 10 (PKAS). The ranges of concentrations in stool were 17.8-2170 µg/g for fidaxomicin and 0-1940 µg/g for OP-1118. Sixty percent (15/25) of patients experienced treatment-emergent adverse events (TEAEs), none of which led to treatment discontinuation or death. Conclusions: Maximum fidaxomicin and OP-1118 plasma concentrations observed in this study population suggest no increase in absorption, compared with patients without IBD. Incidence of TEAEs was similar to previous Phase III trials, suggesting that fidaxomicin is comparatively well tolerated in patients with IBD.

Antiretrovirals, Fractures, and Osteonecrosis in a Large International HIV Cohort.

BACKGROUND: Antiretrovirals (ARVs) affect bone density and turnover, but their effect on risk of fractures and osteonecrosis of the femoral head is less understood. We investigated if exposure to ARVs increases the risk of both bone outcomes. METHODS: EuroSIDA participants were followed to assess fractures and osteonecrosis. Poisson regression identified clinical, laboratory and demographic predictors of either bone outcome. Ever, current, and cumulative exposures to ARVs were assessed. RESULTS: During 86118 PYFU among 11820 included persons (median age 41y, 75% male, median baseline CD4 440/mm3, 70.4% virologically suppressed), there were 619 fractures (incidence/1000 PYFU 7.2; 95% CI 6.6-7.7) and 89 osteonecrosis (1.0; 0.8-1.3). Older age, white race, lower BMI, IV drug use, lower baseline CD4, HCV coinfection, prior osteonecrosis, prior fracture, cardiovascular disease, and recent non-AIDS cancer (last 12 months) were associated with fractures. After adjustment, persons who had ever used tenofovir disoproxil fumarate (TDF) (1.40; 1.15-1.70) or who were currently on TDF (1.25; 1.05-1.49) had higher incidence of fractures. There was no association between cumulative exposure to TDF and fractures (1.08/5 y exposure; 0.94-1.25). No other ARV was associated with fractures (all P > .1). Risk of osteonecrosis was associated with white race, lower nadir CD4, prior osteonecrosis, prior fracture, and prior AIDS. After mutual adjustment, no ARV was associated with osteonecrosis. CONCLUSIONS: In human immunodeficiency virus (HIV) infection, host factors, HIV-specific variables, and comorbidities contribute to risk of fractures and osteonecrosis. Exposure to TDF, but not other ARVs, was an independent risk factor for fractures.

Daptomycin use in patients with osteomyelitis: a preliminary report from the EU-CORE(SM) database.

BACKGROUND: Osteomyelitis is a complex and heterogeneous group of infections that require surgical and antimicrobial interventions. Because treatment failure or intolerance is common, new treatment options are needed. Daptomycin has broad Gram-positive activity, penetrates bone effectively and has bactericidal activity within biofilms. This is the first report on clinical outcomes in patients with osteomyelitis from the multicentre, retrospective, non-interventional European Cubicin(®) Outcomes Registry and Experience (EU-CORE(SM)), a large database on real-world daptomycin use. PATIENTS AND METHODS: In total, 220 patients were treated for osteomyelitis; the population was predominantly elderly, with predisposing baseline conditions such as diabetes and chronic renal/cardiac diseases. RESULTS: Most patients (76%) received prior antibiotic treatment, and first-line treatment failure was the most frequent reason to start daptomycin. Common sites of infection were the knee (22%) or hip (21%), and the most frequently isolated pathogens were Staphylococcus aureus (33%) and coagulase-negative staphylococci (32%). Overall, 52% of patients had surgery, 55% received concomitant antibiotics and 29% received a proportion of daptomycin therapy as outpatients. Clinical success was achieved in 75% of patients. Among patients with prosthetic device-related osteomyelitis, there was a trend towards higher success rates if the device was removed. Daptomycin was generally well tolerated. CONCLUSIONS: This analysis suggests that daptomycin is an effective and well-tolerated treatment option for osteomyelitis and highlights the importance of optimal surgical intervention and appropriate microbiological diagnosis for clinical outcomes.

Association of virus load, CD4 cell count, and treatment with clinical progression in human immunodeficiency virus-infected patients with very low CD4 cell counts.

This study prospectively assessed the impact of treatment modality, virus load, and CD4 cell count of <50 cells/mm(3) on human immunodeficiency virus disease progression. The incidence rate of new AIDS disease or death was 54.8 (95% confidence interval, 48.7-59.9) per 100 person-years of follow-up. Independent predictors related to progression were latest CD4 cell count (relative risk [RR], 0.84/10 mm(3) higher; P<.0001), latest hemoglobin level (RR, 0.79/g/L higher; P<.0001), Pneumocystis carinii pneumonia prophylaxis (RR, 0.49; P<.0001), latest body mass index (RR, 0.93/kg/m(2) higher; P=.002), latest virus load (RR, 1.11/log(10) higher; P=.03), and intensity of treatment (RR, 1.82, P=.004; RR 2.27, P<.0001; RR 2.46, P=.0001; RR 2.33 P<.0006; 5.10, P<.0001, respectively, for 4, 3, 2, 1, or no drugs vs. >or=5 drugs). Although reverse causality cannot be excluded, more intense antiviral treatment appears to decrease the risk of progression in immunocompromised patients.