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BACKGROUND: COVID-19-associated pulmonary aspergillosis (CAPA) has been reported as an important cause of mortality in critically ill patients with an incidence rate ranging from 5% to 35% during the first and second pandemic waves. OBJECTIVES: We aimed to evaluate the incidence, risk factors for CAPA by a screening protocol and outcome in the critically ill patients during the third wave of the pandemic. PATIENTS/METHODS: This prospective cohort study was conducted in two intensive care units (ICU) designated for patients with COVID-19 in a tertiary care university hospital between 18 November 2020 and 24 April 2021. SARS-CoV-2 PCR-positive adult patients admitted to the ICU with respiratory failure were included in the study. Serum and respiratory samples were collected periodically from ICU admission up to CAPA diagnosis, patient discharge or death. ECMM/ISHAM consensus criteria were used to diagnose and classify CAPA cases. RESULTS: A total of 302 patients were admitted to the two ICUs during the study period, and 213 were included in the study. CAPA was diagnosed in 43 (20.1%) patients (12.2% probable, 7.9% possible). In regression analysis, male sex, higher SOFA scores at ICU admission, invasive mechanical ventilation and longer ICU stay were significantly associated with CAPA development. Overall ICU mortality rate was higher significantly in CAPA group compared to those with no CAPA (67.4% vs 29.4%, p < .001). CONCLUSIONS: One fifth of critically ill patients in COVID-19 ICUs developed CAPA, and this was associated with a high mortality.
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COVID-19 , Aspergilosis Pulmonar Invasiva , Aspergilosis Pulmonar , Adulto , COVID-19/complicaciones , COVID-19/epidemiología , Enfermedad Crítica , Humanos , Unidades de Cuidados Intensivos , Aspergilosis Pulmonar Invasiva/complicaciones , Aspergilosis Pulmonar Invasiva/diagnóstico , Aspergilosis Pulmonar Invasiva/epidemiología , Masculino , Pandemias , Estudios Prospectivos , Aspergilosis Pulmonar/complicaciones , SARS-CoV-2RESUMEN
INTRODUCTION: It was previously demonstrated that seasonal influenza incidence was significantly decreased during the COVID-19 pandemic, possibly due to respiratory and hygiene precautions. From this point, we hypothesized that the COVID-19 precautions could lead to a decrease in nosocomial infection rates in oncology inpatient wards. METHODS: We evaluated the nosocomial infection rates in an inpatient palliative oncology ward in the first 3 months of the COVID-19 pandemic in our country and compared this rate with the same time frame of the previous year in our institution. RESULTS: The percentage of nosocomial infections complicating the hospitalization episodes were significantly reduced in the first 3 months of the pandemic compared to the previous year (43 vs. 55 nosocomial infection episodes; 18.6% vs. 32.2%, p = 0.002). The decrease in the nosocomial infections was consistent in the different types of infections, namely pneumonia (4.8% vs. 7.6%), urinary tract infection (5.2% vs. 7.6%), bacteremia (5.2% vs. 7%) and intraabdominal infections (2.6% vs. 3.5%). The median monthly disinfectant use was significantly increased to 98 liters (interquartile range: 82 - 114) in 2020 compared to 72â L (interquartile range: 36 - 72) in 2019 (p = 0.046). CONCLUSION: The continuation of the simple and feasible hygiene and distancing measures for healthcare workers and patient relatives and adaptations for earlier discharge could be beneficial for preventing nosocomial infections in oncology wards. These measures could be implemented routinely even after the COVID-19 pandemic for patient safety, especially in settings with higher nosocomial infection rates like inpatients palliative care units.
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Bacteriemia , COVID-19 , Infección Hospitalaria , Humanos , Infección Hospitalaria/epidemiología , Infección Hospitalaria/prevención & control , Infección Hospitalaria/etiología , COVID-19/epidemiología , COVID-19/prevención & control , Pandemias , Higiene , Bacteriemia/epidemiologíaRESUMEN
BACKGROUND: We aimed to analyze the usefulness of such a reserved area for the admission of the patients' symptoms suggesting COVID-19 and compare the demographic and clinical characteristics of the patients with COVID-19 and without COVID-19 who were admitted to C1 during the first month of the COVID-19 outbreak in our hospital. METHODS: A new area was set up in Hacettepe University Adult Hospital to limit the contact of COVID-19 suspicious patients with other patients, which was named as COVID-19 First Evaluation Outpatient Clinic (C1). C1 had eight isolation rooms and two sampling rooms for SARS-CoV-2 polymerase-chain-reaction (PCR). All rooms were negative-pressurized. Patients who had symptoms that were compatible with COVID-19 were referred to C1 from pretriage areas. All staff received training for the appropriate use of personal protective equipment and were visited daily by the Infection Prevention and Control team. RESULTS: One hundred and ninety-eight (29.4%) of 673 patients who were admitted to C1were diagnosed with COVID-19 between March 20, 2020, and April 19, 2020. SARS-CoV-2 PCR was positive in 142 out of 673 patients. Chest computerized tomography (CT) was performed in 421 patients and COVID-19 was diagnosed in 56 of them based on CT findings despite negative PCR. Four hundred and ninety-three patients were tested for other viral and bacterial infections with multiplex real-time reverse-transcriptase PCR (RTPCR). Blood tests that included complete blood count, renal and liver functions, d-dimer levels, ferritin, C- reactive protein, and procalcitonin were performed in 593 patients. Only one out of 44 healthcare workers who worked at C1 was infected by SARS-CoV-2. DISCUSSION: Early diagnosis of infected patients and ensuring adequate isolation are very important to control the spread of COVID-19. The purpose of setting up the COVID-19 first evaluation outpatient clinic was to prevent the overcrowding of ER due to mild or moderate infections, ensure appropriate distancing and isolation, and enable emergency services to serve for real emergencies. A wellplanned outpatient care area and teamwork including internal medicine, microbiology, and radiology specialists under the supervision of infectious diseases specialists allowed adequate management of the mild-to-moderate patients with suspicion of COVID-19.
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COVID-19 , Adulto , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Turquía/epidemiología , Hospitales Universitarios , Instituciones de Atención AmbulatoriaRESUMEN
We present demographic, clinical, laboratory characteristics and outcomes of the patients with solid malignancies and novel coronavirus disease (COVID-19) collected from the National COVID-19 Registry of Turkey. A total of 1523 patients with a current or past diagnosis of solid tumors and diagnosed with COVID-19 (confirmed with PCR) between 11 March and 20 May 2020 were included. The primary outcome was 30-day mortality. Median age was 61 (range: 18-94), and 752 (49%) were male. The most common types of cancers were breast (19.8%), prostate (10.9%) and colorectal cancer (10.8%). 65% of the patients had at least one comorbidity. At least one COVID-19-directed therapy was given in 73% of the patients.. Hospitalization rate of the patients was 56.6% and intensive care unit admission rate was 11.4%. Seventy-seven (5.1%) patients died within 30 days of diagnosis. The first multivariate model which included only the demographic and clinical characteristics showed older age, male gender and presence of diabetes and receipt of cytotoxic therapy to be associated with increased 30-day mortality, while breast and prostate cancer diagnoses were associated with lower 30-day mortality. In the second set, we further included laboratory parameters. The presence of leukocytosis (OR 6.7, 95% CI 3.3-13.7, P < .001), lymphocytopenia (OR 3,1, 95% CI 1,6-6,1, P = .001) and thrombocytopenia (OR 3,4 95% CI 1,5-8,1, P = .005) were found to be associated with increased 30-day mortality. Relatively lower mortality compared to Western countries and China mainly results from differences in baseline risk factors but may also implicate the importance of intensive supportive care.
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Antifungal stewardship (AFS) is recommended to reduce the inappropriate use of antifungal drugs. In this study, the role of AFS in providing appropriate antifungal therapy was evaluated. This study included three periods, consisting of observation, feedback/education, and daily AFS activities. In the observation period, the use of systemic antifungals was evaluated for a baseline measurement of appropriateness. In the second period, monthly meetings were organized to provide feedback and education to physicians regarding antifungal therapy and the rate of adherence to the clinical guidelines. In the final period, a clinical pharmacist participated in daily ward rounds to evaluate the appropriateness of the antifungal therapy. A scoring system for appropriateness was used for comparison between the three periods. Four hundred eighteen episodes of antifungal therapy were evaluated. Baseline demographics of patients were similar in all three periods for age, gender, and the number of comorbidities. The indications for antifungal use were for prophylaxis in 22.7%, Candida infections in 58.6%, and invasive mold infections in 18.7%. During the third period, 157 (78.9%) recommendations were made and 151 (96.2%) were accepted. The overall appropriateness of antifungal use increased significantly for prophylaxis (30.8%, 17.9%, and 46.3%; P = 0.046) and treatment of fungal diseases (27.8%, 32.4%, and 71.9%; P < 0.001) between the first, second, and third periods, respectively. The 30-day mortality was not significantly changed between the three periods (19%, 15.6%, and 27.5%; P = 0.050). Appropriateness in antifungal therapy can be augmented by the integration of an AFS program. A team-based evaluation of fungal infections and assessment of patients by a clinical pharmacist with a therapeutic perspective may help to increase the quality of antifungal therapy.
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Antifúngicos , Micosis , Antifúngicos/uso terapéutico , Humanos , Micosis/tratamiento farmacológico , Farmacéuticos , Centros de Atención TerciariaRESUMEN
BACKGROUND: The 30-day readmission rate is an important indicator of patient safety and hospital's quality performance. In this study, we aimed to find out the 30-day readmission rate of mild and moderate severity coronavirus disease of 2019 (COVID-19) patients discharged from a tertiary care university hospital and to demonstrate the possible factors associated with readmission. METHODS: This is an observational, single-center study. Epidemiological and clinical data of patients who were hospitalized with a diagnosis of COVID-19 were retrieved from a research database where patient information was recorded prospectively. Readmission data were sought from the hospital information management system and the National Health Information System to detect if the patients were readmitted to any hospital within 30 days of discharge. Adult patients (≥18 years old) hospitalized in COVID-19 wards with a diagnosis of mild or moderate COVID-19 between 20 March 2020 (when the first case was admitted to our hospital) and 26 April 2020 were included. RESULTS: From 26 March to 1 May, there were 154 mild or moderate severity (non-critical) COVID-19 patients discharged from COVID-19 wards, of which 11 (7.1%) were readmitted. The median time of readmission was 8.1 days (interquartile range [IQR] = 5.2). Two patients (18.1%) were categorized to have mild disease and the remaining 9 (81.9%) as moderate disease. Two patients who were over 65 years of age and had metastatic cancers and hypertension developed sepsis and died in the hospital during the readmission episode. Malignancy (18.7% vs. 2.1%, P = 0.04) and hypertension (45.5% vs. 14%, P = 0.02) were more common in those who were readmitted. CONCLUSIONS: This is one of the first studies to report on 30-day readmission rate of COVID-19 in the literature. More comprehensive studies are needed to reveal the causes and predictors of COVID-19 readmissions.
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COVID-19/epidemiología , Readmisión del Paciente/estadística & datos numéricos , Adulto , Anciano , COVID-19/mortalidad , Femenino , Hospitales Universitarios , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Indicadores de Calidad de la Atención de Salud , SARS-CoV-2 , Atención Terciaria de Salud , Turquía/epidemiologíaRESUMEN
COVID-19 infection caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to affect people as a global threat, and the number of cases is increasing every day. Healthcare workers who face potential COVID-19 exposure are at high risk of SARS-CoV-2 transmission. Estimating the prevalence of infection among healthcare professionals, determining the related risk factors and applying effective infection control measures are essential for the continuity of the health system. The aim of this study was to investigate the seroprevalence of SARS-CoV-2 among healthcare workers in our hospital who have participated extensively in the monitoring of COVID-19 patients. In the study, the anti-SARS-CoV-2 IgG antibody test results of 774 healthcare workers between March 24, 2020, and September 10, 2020 were analyzed retrospectively. Age, sex, profession, and the status of being diagnosed with COVID-19 before the antibody test were determined for the healthcare workers in the study. When the anti-SARS-CoV-2 IgG antibody results were evaluated, it was determined that 57 healthcare workers were positive, 708 healthcare workers were negative, and 9 healthcare workers were borderline. The seroprevalence among the workers of our hospital was found to be 7.4%. The antibody positivity rate was 75.6% in individuals diagnosed with COVID-19 by SARS-CoV-2 PCR (polymerase chain reaction) and/or thoracic computed tomography and it was found to be 3.5% in individuals without the diagnosis. The semi-quantitative antibody index values of the healthcare workers who were seropositive and diagnosed with COVID-19 before the test (n= 31) and those who did not (n= 26) were statistically compared and a significant difference was found between the two groups (p<0.01). In our study, the highest seropositivity was observed among residents (12.3%) and among nurses (11.1%), respectively. When the seropositivity rates of the residents and the nurses were compared with other occupational groups, the differences were found to be statistically significant (p= 0.04, p= 0.04, respectively). In conclusion, the seroprevalence of SARS-CoV-2 was determined as 7.4% among healthcare workers in a tertiary hospital with high patient admissions during the COVID-19 pandemic. Considering that SARS-CoV-2 seroprevalence was announced as 0.81% in the press release made by the Ministry of Health of Turkey in July 2020, it is seen that the rate of seroprevalence among health care workers is significantly larger than the community. Determination of the seroprevalence in the general population and large-scale studies are needed for risk assessment in healthcare professionals.
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COVID-19 , SARS-CoV-2 , Personal de Salud , Humanos , Pandemias , Estudios Retrospectivos , Estudios Seroepidemiológicos , Turquía/epidemiologíaRESUMEN
Background/aim: Despite the fact that the COVID-19 pandemic has been going on for over 5 months, there is yet to be a standard management policy for all patients including those with mild-to-moderate cases. We evaluated the role of early hospitalization in combination with early antiviral therapy with COVID-19 patients in a tertiary care university hospital. Materials and methods: This was a prospective, observational, single-center study on probable/confirmed COVID-19 patients hospitalized in a tertiary care hospital on COVID-19 wards between March 20 and April 30, 2020. The demographic, laboratory, and clinical data were collected. Results: We included 174 consecutive probable/confirmed COVID-19 adult patients hospitalized in the Internal Medicine wards of the University Adult Hospital between March 20 and April 30, 2020. The median age was 45.5 (1992) years and 91 patients (52.3%) were male. One hundred and twenty (69%) were confirmed microbiologically, 41 (23.5%) were radiologically diagnosed, and 13 (7.5%) were clinically suspected (negative microbiological and radiological findings compatible with COVID-19); 35 (20.1%) had mild, 107 (61.5%) moderate disease, and 32 (18.4%) had severe pneumonia. Out of 171 cases, 130 (74.3%) showed pneumonia; 80 were typical, and 50 showed indeterminate infiltration for COVID-19. Patients were admitted within a median of 3 days (0-14 days) after symptoms appear. The median duration of hospitalization was 4 days (0-28 days). In this case series, 13.2% patients were treated with hydroxychloroquine alone, 64.9% with hydroxychloroquine plus azithromycin, and 18.4% with regimens including favipiravir. A total of 15 patients (8.5%) were transferred to the ICU. Four patients died (2.2%). Conclusion: In our series, 174 patients were admitted to the hospital wards for COVID-19, 69% were confirmed with PCR and/or antibody test. At the time of admission, nearly one fifth of the patients had severe diseases. Of the patients, 95.4% received hydroxychloroquine alone or in combination. The overall case fatality rate was 2.2%.
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Amidas/uso terapéutico , Antibacterianos/uso terapéutico , Antivirales/uso terapéutico , Azitromicina/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Hospitalización , Hidroxicloroquina/uso terapéutico , Pirazinas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Quimioterapia Combinada , Intervención Médica Temprana , Puntuación de Alerta Temprana , Femenino , Humanos , Unidades de Cuidados Intensivos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Estudios Prospectivos , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: The effect of neuraminidase inhibitor (NAI) treatment on length of stay (LoS) in patients hospitalized with influenza is unclear. METHODS: We conducted a one-stage individual participant data (IPD) meta-analysis exploring the association between NAI treatment and LoS in patients hospitalized with 2009 influenza A(H1N1) virus (A[H1N1]pdm09) infection. Using mixed-effects negative binomial regression and adjusting for the propensity to receive NAI, antibiotic, and corticosteroid treatment, we calculated incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Patients with a LoS of <1 day and those who died while hospitalized were excluded. RESULTS: We analyzed data on 18 309 patients from 70 clinical centers. After adjustment, NAI treatment initiated at hospitalization was associated with a 19% reduction in the LoS among patients with clinically suspected or laboratory-confirmed influenza A(H1N1)pdm09 infection (IRR, 0.81; 95% CI, .78-.85), compared with later or no initiation of NAI treatment. Similar statistically significant associations were seen in all clinical subgroups. NAI treatment (at any time), compared with no NAI treatment, and NAI treatment initiated <2 days after symptom onset, compared with later or no initiation of NAI treatment, showed mixed patterns of association with the LoS. CONCLUSIONS: When patients hospitalized with influenza are treated with NAIs, treatment initiated on admission, regardless of time since symptom onset, is associated with a reduced LoS, compared with later or no initiation of treatment.
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Antivirales/uso terapéutico , Inhibidores Enzimáticos/uso terapéutico , Subtipo H1N1 del Virus de la Influenza A , Gripe Humana/tratamiento farmacológico , Gripe Humana/epidemiología , Tiempo de Internación , Neuraminidasa/antagonistas & inhibidores , Pandemias , Adolescente , Corticoesteroides/uso terapéutico , Adulto , Anciano , Antibacterianos/uso terapéutico , Niño , Inhibidores Enzimáticos/farmacología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenRESUMEN
In spite of the fact that Plasmodium vivax is the leading causative agent of malaria in our country, imported malaria cases have been reported, recently. In this report, two malaria cases originated from sub-Saharan Africa, and their diagnostic and therapeutic approaches were aimed to be presented. First case, 45-year-old male, who has been working in Republic of Ghana, was admitted to Hacettepe University Hospitals Emergency Service with complaints of fever, sweating and shivering, after returning to Turkey. On admission, his general condition was fine and his physical examination revealed no pathological finding. After his admission, a fever episode occured and his blood tests revealed anemia, trombocytopenia and increased alkaline phosphatase level. Second case, 39-year-old-male admitted to the emergency service with the complaints of fever, shivering and myalgia. His physical examination revealed decreased breath sounds and splenomegaly, his laboratory tests resulted in pansitopenia and elevated liver enzymes. In the thick blood smears of the patients ring formed young trophozoites are detected and in the thin films multiple ring forms demonstrated in one erythrocyte with the absence of mature trophozoites and schizont forms, which were compatible with falciparum malaria. The rapid antigen test (Digamed, Belgium) of the second case found to be positive for both Plasmodium falciparum and P.vivax and this patient followed-up in intensive care unit due to his deterioration of general condition, respiratory distress, hematuria and change of consciousness. Neither cases were commenced on malaria prophylaxis. Both patients have been in countries which chloroquine resistance is commonly seen, they were treated with artemether/lumefantrine as current World Health Organization recommended. Targeting hypnozoites of P.vivax, primaquine was added to the therapy of the second patient. Both patients resulted in cure. In conclusion, while travelling to endemic countries, people should be informed about the importance of malaria prophylaxis and prophylaxis should be commenced immediately and continued appropriately. Additionally, malaria should always be considered in the differential diagnosis of high fever for the patients who admitted to the hospital with a travelling history to these countries.
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Antimaláricos , Combinación Arteméter y Lumefantrina , Malaria , Primaquina , Adulto , África del Sur del Sahara , Antimaláricos/uso terapéutico , Combinación Arteméter y Lumefantrina/uso terapéutico , Enfermedades Transmisibles Importadas/diagnóstico , Enfermedades Transmisibles Importadas/tratamiento farmacológico , Enfermedades Transmisibles Importadas/parasitología , Enfermedades Transmisibles Importadas/prevención & control , Humanos , Malaria/diagnóstico , Malaria/tratamiento farmacológico , Malaria/parasitología , Malaria/prevención & control , Masculino , Persona de Mediana Edad , Plasmodium falciparum , Plasmodium vivax , Primaquina/uso terapéutico , Viaje , Resultado del Tratamiento , TurquíaRESUMEN
Carbapenem resistant Acinetobacter baumannii is a bacterium that causes various hospital acquired infections, primarily ventilator-associated pneumonia and bloodstream infections. The multidrug resistance problem of the bacteria all over the world, is also a problem in our center. As the treatment options are decreasing combination therapies become a current issue. It is believed that in vitro synergy tests may guide to the selection of antibiotic combinations. The aim of this study was to present the antibiotic combinations used in the treatment of carbapenem resistant A.baumannii infections and the synergy test results of these combinations. A total of 71 carbapenem-resistant A.baumannii isolates from various clinical samples of patients in Hacettepe University Adult and Oncology Hospitals was included in the study. All isolates were from nosocomial infections that were being requested for synergy testing by the consulting physicians in the Department of Infectious Diseases and Clinical Microbiology between January 2002 and December 2016. Only one isolate from one patient was included in the analysis. The synergy test for these isolates was performed by E-test method. Of the total, 41 (58%) isolates were from various clinical samples of patients in intensive care units and 30 (42%) were from patients in different wards. Twenty-three of the isolates were obtained from bronchoalveolar lavage (BAL) fluid, 18 from pus, 14 from deep tracheal aspirate, 6 from central venous catheter, 5 from blood and 5 from other various samples. The fractional inhibition concentration (FIC) index for each combination was calculated and the results were interpreted as synergistic, additive, indifferent and antagonist. A total of 38 different combinations of antibiotics were tested. According to the frequency of synergistic activity, the combinations were; meropenem-colistin (11/12), meropenem-amikacin (7/9), meropenem-tobramycin (9/13), rifampicin-colistin (7/11), cefaperazone-sulbactam-tobramycin (8/16) and sefaperazon-sulbactam-amikacin (5/10). The most common antagonistic combinations were tigecyclin-colistin (2/6), meropenem-tobramycin (3/13), cefepim-tobramycin (4/19), rifampicin-colistin (2/11) combinations. In our center, different combinations of antibiotics are being used for the treatment of carbapenem-resistant A.baumannii due to the changing and increasing antibiotic resistance of the bacteria over the years. Sensitivity tests as well as synergy tests are used when selecting different combinations of antibiotics. However generalizability of the synergistic effect of combinations is limited. It is important to repeat these studies at regular intervals. In addition there is also a need for further studies to evaluate the correlation between in vitro laboratory results and in vivo clinical compliance.
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Infecciones por Acinetobacter , Acinetobacter baumannii , Infecciones por Acinetobacter/tratamiento farmacológico , Acinetobacter baumannii/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Sinergismo Farmacológico , Quimioterapia Combinada , Humanos , Pruebas de Sensibilidad Microbiana , TurquíaRESUMEN
PURPOSE OF REVIEW: Carbapenem-resistant Enterobacteriaceae (CRE) is a worldwide challenge and associated with a high mortality rate in critically ill patients. This review focused on rapid diagnosis, optimization of antimicrobial therapy, and implication of effective infection control precautions to reduce impact of CRE on vulnerable patients. RECENT FINDINGS: Several new diagnostic assays have recently been described for the early diagnosis of CRE. Retrospective studies are supportive for colistin plus meropenem combination for the treatment of CRE infections; however, solid evidence is still lacking. Ceftazidime-avibactam may be an effective therapeutic agent for infections caused by carbapenem-hydrolyzing oxacillinase-48 and Klebsiella pneumoniae carbapenamase-producing Enterobacteriaceae, but not for New Delhi metallo-ß-lactamase producers. Gastrointestinal screening may permit early identification of patients with CRE infections. There is not enough evidence to recommend selective digestive decontamination for CRE carriers. SUMMARY: The information for rapid diagnosis of CRE is accumulating. There are new agents with high in-vitro activity against CRE, but clinical experience is limited to case reports. Active surveillance with a high rate of compliance to basic infection control precautions seems to be the best approach to reduce the impact of CRE on vulnerable patients.
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Carbapenémicos/uso terapéutico , Infecciones por Enterobacteriaceae/diagnóstico , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Enterobacteriaceae/efectos de los fármacos , Resistencia betalactámica , Antibacterianos/uso terapéutico , Compuestos de Azabiciclo/uso terapéutico , Ceftazidima/uso terapéutico , Colistina/uso terapéutico , Enfermedad Crítica , Combinación de Medicamentos , Quimioterapia Combinada , Enterobacteriaceae/enzimología , Humanos , Meropenem , Estudios Retrospectivos , Tienamicinas/uso terapéutico , beta-Lactamasas/biosíntesisRESUMEN
Bacillus anthracis produces a binary toxin composed of protective antigen (PA) and one of two subunits, lethal factor (LF) or edema factor (EF). Most studies have concentrated on induction of toxin-specific antibodies as the correlate of protective immunity, in contrast to which understanding of cellular immunity to these toxins and its impact on infection is limited. We characterized CD4+ T cell immunity to LF in a panel of humanized HLA-DR and DQ transgenic mice and in naturally exposed patients. As the variation in antigen presentation governed by HLA polymorphism has a major impact on protective immunity to specific epitopes, we examined relative binding affinities of LF peptides to purified HLA class II molecules, identifying those regions likely to be of broad applicability to human immune studies through their ability to bind multiple alleles. Transgenics differing only in their expression of human HLA class II alleles showed a marked hierarchy of immunity to LF. Immunogenicity in HLA transgenics was primarily restricted to epitopes from domains II and IV of LF and promiscuous, dominant epitopes, common to all HLA types, were identified in domain II. The relevance of this model was further demonstrated by the fact that a number of the immunodominant epitopes identified in mice were recognized by T cells from humans previously infected with cutaneous anthrax and from vaccinated individuals. The ability of the identified epitopes to confer protective immunity was demonstrated by lethal anthrax challenge of HLA transgenic mice immunized with a peptide subunit vaccine comprising the immunodominant epitopes that we identified.
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Vacunas contra el Carbunco , Carbunco/prevención & control , Antígenos Bacterianos/inmunología , Toxinas Bacterianas/inmunología , Linfocitos T CD4-Positivos/inmunología , Antígenos HLA/genética , Inmunidad Celular/genética , Polimorfismo Genético , Enfermedades Cutáneas Bacterianas/prevención & control , Adulto , Secuencia de Aminoácidos , Animales , Carbunco/inmunología , Vacunas contra el Carbunco/química , Vacunas contra el Carbunco/uso terapéutico , Antígenos Bacterianos/química , Toxinas Bacterianas/química , Mapeo Epitopo , Antígenos HLA/inmunología , Humanos , Epítopos Inmunodominantes/química , Epítopos Inmunodominantes/inmunología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Modelos Moleculares , Terapia Molecular Dirigida , Enfermedades Cutáneas Bacterianas/inmunología , Adulto JovenRESUMEN
Saprochaete capitata is a very rare pathogen that causes invasive disease particularly in patients with haematological malignancies. We recognised a clustering of S. capitata fungaemia in recent years. So, we report our 6-year surveillance study of fungaemia among patients with haematological malignancies and haematopoietic stem cell transplant. We performed a retrospective and observational study. Hospitalised patients aged >18 years with haematological malignancies were included in the study. A total of 51 fungaemia episodes of 47 patients were analysed. The characteristics of fungaemia in patients with S. capitata compared to patients with candidemia. Median duration of neutropenia was 21.5 days in patients with S. capitata fungaemia, whereas this duration was significantly shorter in patients with candidemia (8 days). Interval between first and last positive culture was significantly longer in patients with S. capitata fungaemia (P < 0.05). Previous use of caspofungin was significantly more common in patients with S. capitata fungaemia. Thirty-day mortality was found 40% for patients with candidemia, whereas it was 39% for patients with S. capitata. In conclusion, despite its limitations this study showed that a novel and more resistant yeast-like pathogen become prevalent due to use of caspofungin in patients with long-lasting neutropenia which was the most noteworthy finding of this 6-year surveillance study.
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Fungemia/complicaciones , Fungemia/epidemiología , Neoplasias Hematológicas/complicaciones , Saccharomycetales , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Candidemia/complicaciones , Candidemia/epidemiología , Candidemia/mortalidad , Caspofungina , Equinocandinas/efectos adversos , Equinocandinas/uso terapéutico , Monitoreo Epidemiológico , Femenino , Fungemia/microbiología , Fungemia/mortalidad , Neoplasias Hematológicas/microbiología , Humanos , Lipopéptidos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Neutropenia/microbiología , Estudios Retrospectivos , Saccharomycetales/efectos de los fármacos , Saccharomycetales/aislamiento & purificación , Factores de Tiempo , Adulto JovenRESUMEN
One of the most problematic issues in hematological malignancies is the diagnosis of invasive fungal diseases. Especially, the difficulty of mycological diagnosis and the necessity of immediate intervention in molds have led to the adoption of "surrogate markers" that do not verify but rather strongly suggest fungal infection. The markers commonly used are galactomannan (GM), beta-glucan, and imaging methods. Although there are numerous studies on these diagnostic approaches, none of these markers serve as a support for the clinician, as is the case in human immunodeficiency virus (HIV) or cytomegalovirus (CMV) infections. This paper has been prepared to explain the diagnostic tests. As molecular tests have not been standardized and are not used routinely in the clinics, they will not be mentioned here.
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Objective: The rise of antibiotic-resistant organisms necessitates the implementation of rapid identification (ID) and antibiotic susceptibility testing (AST) methods for patient management. We aimed to analyze how rapid ID and AST reporting influenced clinicians' treatment decisions. Materials and Methods: Bacteria were identified directly from positive blood cultures (BC) using serum separator tubes and MALDI-TOF MS. EUCAST rapid antibiotic susceptibility testing (RAST) method was performed for AST. The impact of rapid ID and AST reports on clinician treatment decisions was evaluated through clinical documentation. The appropriateness of antimicrobial therapy and interventions was assessed according to institutional antimicrobial prescribing guidelines, AST results, and clinical data. Results: A total of 128 BC bottles from 86 patients underwent processing. The rapid ID method was successful in 105 (82.1%) bottles obtained from 76 patients. The rapid ID results were reviewed by the Infectious Diseases Team on the same day for 55 (72.4%) of the 76 patients. Following the evaluation, new treatments or interventions were recommended for 28 (36.8%) patients. RAST results were available for 24 patients. The susceptibility profile of seven patients was assessed by the Infectious Diseases Team on the same day. Antimicrobial treatment was escalated in four cases, and de-escalation was made in two based on RAST results. If all rapid results had been assessed, adjustments could have been made for eight (10.5%) and eleven (14.5%) more patients, according to ID and RAST results, respectively. Conclusion: Implementation of rapid ID and AST may contribute to patient management. Although rapid reporting was made, some results were not evaluated by the clinician on the same day, indicating that communication between the clinician and the laboratory needs to be strengthened.
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It is well-established that Infectious Diseases consultation (IDC) enhances the prognosis of bloodstream infections. However, it is unclear if adoption of an institutional sepsis protocol would lead to any further improvement in a setting where IDC and infectious diseases approval (IDA) - available throughout 7 days/24 hours -are mandatory for administering broad spectrum antibiotics. We aimed to evaluate the influence of the institutional sepsis protocol developed by Department of Infectious Diseases and Clinical Microbiology on the selection of appropriate empirical antibiotics by IDC through focusing on patients who had bloodstream infections caused by Extended-spectrum ß-lactamase (ESBL) producing Escherichia coli and Klebsiella pneumoniae, which poses a therapeutic challenge. One hundred and fifty-three adult patients (58 patients in the pre-protocol period and 95 patients in the post-protocol period), who received empirical antibiotic treatment for ESBL-producing E. coli and K. pneumoniae, in whom at least one systemic antibiotic was started either on the day blood cultures were drawn or not later than 24 hours were included in the study, retrospectively. The primary outcome was whether the empirical treatment regimen included a carbapenem that was accepted as the appropriate treatment based on the results of the MERINO trial. Secondary outcomes included empirical treatment based on pre-defined risk factors suggesting multidrug resistance (MDR), 30-day inpatient mortality, and appropriate antibacterial treatment according to antimicrobial susceptibility test (AST) results. The median age (Interquartile range) was 61 (48-70.5) years and 76 (49.7%) out of 153 patients were male. The patients in the post-protocol period were older compared to the pre-protocol period (54 years vs 64 years, p = 0.045). The Charlson Comorbidity Index was higher during the post-protocol period compared to the pre-protocol period (4 vs 5, p=0.038). At least one risk factor for MDR bacteria infection was present in 147 (96.1%) of the 153 patients. While the rate of risk factors for MDR bacteria infections did not differ significantly between the pre-protocol and post-protocol periods, the post-protocol period showed a significantly higher level of appropriate antibiotic treatment according to the presence of MDR risk factors compared to the pre-protocol period (44.8% vs 64.2%, p=0.019). There was a significant increase in the use of carbapenems in the post-protocol period compared to the pre-protocol period (34.5% vs. 56.8%, p=0.007). When the subgroup of patients who were likely to have infection caused by ESBL-producing bacteria is taken into consideration, the carbapenem use was more frequent in the post-protocol period (37.8% vs 68.9%, p=0.002). The rate of appropriate empirical treatment according to AST was not statistically different between pre-protocol and post-protocol period. The 30-day mortality rates were similar in both periods (24.1% vs 31.5, p=0.33). However, the rate of susceptibility to piperacillin-tazobactam was statistically higher in the pre-protocol period (82.6% vs 46.2%, p=0.016) when 39.7% of the patients received piperacillin-tazobactam as the empirical treatment. This study highlights the significance of using a structured protocol to attain appropriate empirical treatment for patients suspected of sepsis, even in a setting where IDC is readily available.
Asunto(s)
Bacteriemia , Enfermedades Transmisibles , Infecciones por Escherichia coli , Infecciones por Klebsiella , Sepsis , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , beta-Lactamasas , Carbapenémicos , Enfermedades Transmisibles/tratamiento farmacológico , Escherichia coli , Infecciones por Escherichia coli/tratamiento farmacológico , Hospitales , Infecciones por Klebsiella/microbiología , Combinación Piperacilina y Tazobactam/uso terapéutico , Derivación y Consulta , Estudios Retrospectivos , Sepsis/tratamiento farmacológico , Ensayos Clínicos como AsuntoRESUMEN
Acinetobacter baumannii, a notable drug-resistant bacterium, often induces severe infections in healthcare settings, prompting a deeper exploration of treatment alternatives due to escalating carbapenem resistance. This study meticulously examined clinical, microbiological, and molecular aspects related to in-hospital mortality in patients with carbapenem-resistant A. baumannii (CRAB) bloodstream infections (BSIs). From 292 isolates, 153 cases were scrutinized, reidentified through matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS), and evaluated for antimicrobial susceptibility and carbapenemase genes via multiplex polymerase chain reaction (PCR). Utilizing supervised machine learning, the study constructed models to predict 14- and 30-day mortality rates, revealing the Naïve Bayes model's superior specificity (0.75) and area under the curve (0.822) for 14-day mortality, and the Random Forest model's impressive recall (0.85) for 30-day mortality. These models delineated eight and nine significant features for 14- and 30-day mortality predictions, respectively, with "septic shock" as a pivotal variable. Additional variables such as neutropenia with neutropenic days prior to sepsis, mechanical ventilator support, chronic kidney disease, and heart failure were also identified as ranking features. However, empirical antibiotic therapy appropriateness and specific microbiological data had minimal predictive efficacy. This research offers foundational data for assessing mortality risks associated with CRAB BSI and underscores the importance of stringent infection control practices in the wake of the scarcity of new effective antibiotics against resistant strains. The advanced models and insights generated in this study serve as significant resources for managing the repercussions of A. baumannii infections, contributing substantially to the clinical understanding and management of such infections in healthcare environments.