RESUMO
B-cell-depleting therapies may lead to prolonged disease and viral shedding in individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and this viral persistence raises concern for viral evolution. We report sequencing of early and late samples from a 335-day infection in an immunocompromised patient. The virus accumulated a unique deletion in the amino-terminal domain of the spike protein, and complete deletion of ORF7b and ORF8, the first report of its kind in an immunocompromised patient. Unique viral mutations found in this study highlight the importance of analyzing viral evolution in protracted SARS-CoV-2 infection, especially in immunosuppressed hosts.
Assuntos
COVID-19 , SARS-CoV-2 , Linfócitos B , Humanos , Hospedeiro Imunocomprometido , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética , Eliminação de Partículas ViraisRESUMO
Increasing antimicrobial resistance and medical device-related infections have led to a renewed interest in phage therapy as an alternative or adjunct to conventional antimicrobials. Expanded access and compassionate use cases have risen exponentially but have varied widely in approach, methodology, and clinical situations in which phage therapy might be considered. Large gaps in knowledge contribute to heterogeneity in approach and lack of consensus in many important clinical areas. The Antibacterial Resistance Leadership Group (ARLG) has convened a panel of experts in phage therapy, clinical microbiology, infectious diseases, and pharmacology, who worked with regulatory experts and a funding agency to identify questions based on a clinical framework and divided them into three themes: potential clinical situations in which phage therapy might be considered, laboratory testing, and pharmacokinetic considerations. Suggestions are provided as answers to a series of questions intended to inform clinicians considering experimental phage therapy for patients in their clinical practices.
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Bacteriófagos , Terapia por Fagos , Ensaios de Uso Compassivo , Farmacorresistência Bacteriana , HumanosRESUMO
Serious bacterial infections (SBI) can lead to devastating complications with CD19 CAR T cells and cytokine release syndrome (CRS). Little is known about consequences of and risk factors for SBI with novel CAR T-cell constructs or with CRS complicated by HLH-like toxicities. We report on three patients with B-cell acute lymphoblastic leukemia treated with CD22 CAR T cells who developed SBI and CRS-associated HLH. Serum cytokine profiling revealed sustained elevations well beyond CRS resolution, suggesting ongoing systemic inflammation. Heightened inflammatory states converging with SBI contribute to poor outcomes, and recognition and prevention of extended inflammation may be needed to improve outcomes.
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Bacteriemia , Síndrome da Liberação de Citocina , Linfo-Histiocitose Hemofagocítica , Antígenos CD19 , Bacteriemia/imunologia , Bacteriemia/microbiologia , Síndrome da Liberação de Citocina/imunologia , Humanos , Imunoterapia Adotiva , Linfo-Histiocitose Hemofagocítica/imunologia , Linfo-Histiocitose Hemofagocítica/microbiologia , Receptores de Antígenos Quiméricos , Linfócitos TRESUMO
Human cytomegalovirus (CMV) infection and disease remains a significant cause of morbidity and mortality for hematopoietic cell transplantation (HCT) recipients. Disruption of or weak reconstitution of virus-specific cellular immune function, such as with certain HCT approaches, poses significant risk for CMV-related complications. The incidence of and risk factors for CMV infection and the nature of CMV disease were evaluated retrospectively among 356 consecutive HCT recipients transplanted at the National Institutes of Health using all graft sources, including bone marrow, peripheral blood stem cell (PBSC), and umbilical cord blood (UCB), and a range of in vivo and ex vivo approaches for graft-versus-host disease (GVHD) prophylaxis. The cumulative incidence of CMV infection was higher for CMV-seropositive recipients at 33%, regardless of donor CMV serostatus. Patients transplanted with CMV-seropositive donors had a significantly shorter duration of antiviral therapy. Among graft sources UCB was associated with the highest cumulative incidence of CMV infection at 65% and significantly longer treatment duration at a median of 36days, whereas PBSC HCT was associated with the lowest incidence at 26% and the shortest CMV treatment duration at a median of 21days. There were significant differences in the cumulative incidence of CMV infection by T cell manipulation strategy when systemic steroids were included as a risk-modifying event. Over one-third of CMV infections occurred in the setting of systemic steroid administration. CMV disease occurred in 5% of HCT recipients, with 70% of cases in the setting of treatment for GVHD. Although factors related to serostatus, graft source, and GVHD prophylaxis were associated with varied CMV infection incidence, unplanned post-HCT corticosteroid therapy contributed greatly to the incidence of both CMV infection and disease across HCT approaches, highlighting this post-HCT intervention as a key time to potentially tailor the approach to monitoring, preemptive therapy, and even prophylaxis.
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Infecções por Citomegalovirus/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Adulto , Antivirais/uso terapêutico , Infecções por Citomegalovirus/etiologia , Feminino , Doença Enxerto-Hospedeiro/complicações , Doença Enxerto-Hospedeiro/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , National Institutes of Health (U.S.) , Estudos Retrospectivos , Fatores de Risco , Esteroides/efeitos adversos , Doadores de Tecidos , Estados UnidosRESUMO
BACKGROUND: Clinical approach to ventilator-associated pneumonia (VAP) in the neurocritical care unit (NCCU) varies widely among physicians despite training and validated criteria. METHODS: Prospective observational study of all mechanically ventilated patients with suspected VAP over 18 months in an academic NCCU. Patients meeting VAP criteria by a surveillance program (SurvVAP) were compared to treated patients who did not meet surveillance criteria (ClinVAPonly). We identified appropriate/potentially inappropriate antibiotic treatment and factors associated with excessive antibiotic days (EAD). RESULTS: Of 622 ventilated patients, 83 cases were treated as VAP. Of these, 26 (31.3 %) had VAP by CDC criteria (SurvVAP) (VAP rate = 7.3 cases/1,000 ventilator days). Clinical features significantly more prevalent in SurvVAP cases (vs. ClinVAPonly) were change in sputum character, tachypnea, oxygen desaturation, persistent infiltrate on chest X-ray and higher clinical pulmonary infection score, but not positive sputum culture. Treatment with pneumonia-targeted antibiotics for >8 days was significantly more common in ClinVAPonly versus SurvVAP patients (73.7 vs. 30.8 %, p < 0.001) even after excluding patients with other infections (p = 0.001). Based on current guidelines, the ClinVAPonly group contributed 225 EAD, including 38 vancomycin days, 70 piperacillin-tazobactam days and 85 cephalosporin days with cost figure over four times that of EAD in SurvVAP group. No pre-specified factors were associated with continued VAP treatment beyond 8 days. CONCLUSIONS: Incongruency between clinically and surveillance-defined VAP is common in acute neurological disease although outcomes did not differ between groups. Clinician behaviors rather than clinical factors may contribute to prolonged prescribing.
Assuntos
Anti-Infecciosos/uso terapêutico , Cuidados Críticos/estatística & dados numéricos , Unidades de Terapia Intensiva/estatística & dados numéricos , Doenças do Sistema Nervoso/epidemiologia , Pneumonia Associada à Ventilação Mecânica/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/terapia , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Estudos ProspectivosRESUMO
OBJECTIVES: The optimal duration of antibiotic therapy for uncomplicated Gram-negative bacteraemia remains undefined. Our objective was to compare clinical outcomes of receiving short (7-10 days) versus prolonged (>10 days) durations of antibiotic therapy for children with uncomplicated Gram-negative bacteraemia. METHODS: We conducted a retrospective cohort study of children with uncomplicated Gram-negative bacteraemia at The Johns Hopkins Hospital between 2002 and 2012. We estimated the risk of bacteraemic relapse among children who received short versus prolonged durations of antibiotic therapy using 1:1 nearest neighbour propensity score matching without replacement prior to performing regression analysis. RESULTS: There were 170 matched pairs that were well balanced on baseline covariates. The median duration of therapy in the short and prolonged courses was 10 days (IQR 10-10) and 14 days (IQR 14-17), respectively. The 30 day mortality was similar between the groups (OR 1.12; 95% CI 0.96-1.21). A prolonged duration of antibiotic therapy did not reduce the relapse risk compared with shorter durations (adjusted hazard ratio 0.67; 95% CI 0.35-1.27). Similarly, each additional day of antibiotic therapy was not protective against relapse risk (adjusted hazard ratio 0.99 per additional day; 95% CI 0.92-1.03). There was a trend towards an increased subsequent risk of candidaemia in children receiving longer treatment durations (hazard ratio 2.44; 95% CI 0.97-6.19). CONCLUSIONS: Antibiotic treatment for more than 10 days for uncomplicated bacteraemia in children does not reduce the risk of microbiological relapse compared with shorter-course therapy, but may be associated with an increased risk of candidaemia. Our findings need to be confirmed in a larger, prospective study.
Assuntos
Antibacterianos/administração & dosagem , Bacteriemia/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Adolescente , Bacteriemia/epidemiologia , Candidemia/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Tratamento Farmacológico/métodos , Feminino , Infecções por Bactérias Gram-Negativas/epidemiologia , Humanos , Lactente , Masculino , Recidiva , Estudos Retrospectivos , Medição de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
Prototheca wickerhamii is a rare cause of cutaneous and systemic infection that requires long treatment courses with potentially toxic medications. We describe a patient with cutaneous protothecosis refractory to triazole monotherapy who experienced clinical and radiographic improvement with the novel oral lipid nanocrystal formulation of amphotericin B without experiencing toxicity.
RESUMO
Congenital cytomegalovirus (CMV) is a leading cause of non-genetic sensorineural hearing loss and neurodevelopmental disabilities among US children. Studies using administrative healthcare databases have identified infants with congenital CMV using diagnostic codes from the International Classification of Diseases, Ninth and Tenth Revision, Clinical Modification. Using Cerner Health Facts deidentified electronic health records, we assessed the sensitivity of CMV diagnostic codes among infants with laboratory confirmed congenital CMV infection (i.e. a positive CMV laboratory test - polymerase chain reaction, direct fluorescent antibody, or culture from urine, saliva, respiratory secretion or blood samples, or IgM serology - within 21 days of life). During 2010-2017, 668 congenital CMV cases were identified among 7,517,207 infants with encounters within 21 days of life, or 0.89 cases per 10,000 infants. The sensitivity of CMV diagnostic codes assigned within 21 and 90 days of life was 10.3% (95% CI: 8.2-12.9) and 11.1% (95% CI: 8.9-13.7), respectively.
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Infecções por Citomegalovirus , Perda Auditiva Neurossensorial , Criança , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/epidemiologia , Registros Eletrônicos de Saúde , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/epidemiologia , Humanos , Lactente , Diagnóstico Ausente , SalivaRESUMO
OBJECTIVE: To report a novel case of atrial flutter associated with carboplatin administration and review chemotherapy-related cardiac toxicities, focusing on platinum-containing compounds. CASE REPORT: A 69-year-old man with extensive small cell lung cancer and asymptomatic cardiovascular and cerebrovascular disease was inconsistently adherent to his medication regimen. While undergoing carboplatin infusion, he developed atrial flutter. He had no other immediate arrhythmogenic causes of atrial flutter and the arrhythmia spontaneously reverted to sinus rhythm after 24 hours. His condition remained stable until he died 8 days later. The cause of death was unknown and the family declined postmortem examination. DISCUSSION: Although this patient's cardiac history and nonadherence to his medications may have increased his susceptibility to develop atrial arrhythmias, the Naranjo probability scale reveals a possible relationship between atrial flutter and infusion of carboplatin. A literature search revealed other adverse cardiac events due to platinum compounds; however, to our knowledge, this case is the first to describe an association with atrial flutter. A definitive causal link cannot be determined, but this may have been the result of a direct arrhythmogenic effect of treatment or to a novel hypersensitivity reaction. Given the potential deleterious impact of drug-induced arrhythmias, we have reported this case to the Food and Drug Administration as a new adverse effect of carboplatin. CONCLUSIONS: Providers should consider cardiac monitoring during carboplatin infusion in patients with known cardiac disease or at high risk of cardiac complications.
Assuntos
Antineoplásicos/efeitos adversos , Flutter Atrial/induzido quimicamente , Carboplatina/efeitos adversos , Idoso , Antineoplásicos/administração & dosagem , Carboplatina/administração & dosagem , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológicoRESUMO
Infections are a known complication of chimeric antigen receptor (CAR) T-cell therapy with data largely emerging from CD19 CAR T-cell targeting. As CAR T-cell therapy continues to evolve, infection risks and management thereof will become increasingly important to optimize outcomes across the spectrum of antigens and disease targeted. We retrospectively characterized infectious complications occurring in 162 children and adults treated among 5 phase 1 CAR T-cell clinical trials. Trials included targeting of CD19, CD22, disialoganglioside (GD2) or B-cell maturation antigen (BCMA). Fifty-three patients (32.7%) had 76 infections between lymphocyte depleting (LD) chemotherapy and day 30 (D30); with the majority of infections (61, 80.3%) occurring between day 0 (D0) and D30. By trial, the highest proportion of infections was seen with CD22 CAR T cells (n = 23/53; 43.4%), followed by BCMA CAR T cells (n = 9/24; 37.5%). By disease, patients with multiple myeloma had the highest proportion of infections (9/24; 37.5%) followed by acute lymphoblastic leukemia (36/102; 35.3%). Grade 4 infections were rare (n = 4; 2.5%). Between D0 and D30, bacteremia and bacterial site infections were the most common infection type. In univariate analysis, increasing prior lines of therapy, recent infection within 100 days of LD chemotherapy, corticosteroid or tocilizumab use, and fever and neutropenia were associated with a higher risk of infection. In a multivariable analysis, only prior lines of therapy and recent infection were associated with higher risk of infection. In conclusion, we provide a broad overview of infection risk within the first 30 days post infusion across a host of multiple targets and diseases, elucidating both unique characteristics and commonalities highlighting aspects important to improving patient outcomes.
Assuntos
Imunoterapia Adotiva , Mieloma Múltiplo , Antígenos CD19 , Humanos , Estudos Retrospectivos , Linfócitos TRESUMO
BACKGROUND: B-cell depleting therapies may lead to protracted disease and prolonged viral shedding in individuals infected with SARS-CoV-2. Viral persistence in the setting of immunosuppression raises concern for viral evolution. METHODS: Amplification of sub-genomic transcripts for the E gene (sgE) was done on nasopharyngeal samples over the course of 355 days in a patient infected with SARS-CoV-2 who had previously undergone CAR T cell therapy and had persistently positive SARS-CoV-2 nasopharyngeal swabs. Whole genome sequencing was performed on samples from the patient's original presentation and 10 months later. RESULTS: Over the course of almost a year, the virus accumulated a unique in-frame deletion in the amino-terminal domain of the spike protein, and complete deletion of ORF7b and ORF8, the first report of its kind in an immunocompromised patient. Also, minority variants that were identified in the early samples-reflecting the heterogeneity of the initial infection-were found to be fixed late in the infection. Remdesivir and high-titer convalescent plasma treatment were given, and the infection was eventually cleared after 335 days of infection. CONCLUSIONS: The unique viral mutations found in this study highlight the importance of analyzing viral evolution in protracted SARS-CoV-2 infection, especially in immunosuppressed hosts, and the implication of these mutations in the emergence of viral variants. SUMMARY: We report an immunocompromised patient with persistent symptomatic SARS-CoV-2 infection for 335 days. During this time, the virus accumulated a unique in-frame deletion in the spike, and a complete deletion of ORF7b and ORF8 which is the first report of its kind in an immunocompromised patient.
RESUMO
As clinical advances with chimeric antigen receptor (CAR) T cells are increasingly described and the potential for extending their therapeutic benefit grows, optimizing the implementation of this therapeutic modality is imperative. The recognition and management of cytokine release syndrome (CRS) marked a milestone in this field; however, beyond the understanding gained in treating CRS, a host of additional toxicities and/or potential late effects of CAR T cell therapy warrant further investigation. A multicentre initiative involving experts in paediatric cell therapy, supportive care and/or study of late effects from cancer and haematopoietic stem cell transplantation was convened to facilitate the comprehensive study of extended CAR T cell-mediated toxicities and establish a framework for new systematic investigations of CAR T cell-related adverse events. Together, this group identified six key focus areas: extended monitoring of neurotoxicity and neurocognitive function, psychosocial considerations, infection and immune reconstitution, other end organ toxicities, evaluation of subsequent neoplasms, and strategies to optimize remission durability. Herein, we present the current understanding, gaps in knowledge and future directions of research addressing these CAR T cell-related outcomes. This systematic framework to study extended toxicities and optimization strategies will facilitate the translation of acquired experience and knowledge for optimal application of CAR T cell therapies.
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Imunoterapia Adotiva/efeitos adversos , Neoplasias/terapia , Biomarcadores/sangue , Criança , Síndrome da Liberação de Citocina/etiologia , Humanos , Infecções/etiologia , Neoplasias/psicologia , Neuroimagem/métodos , Síndromes Neurotóxicas/diagnóstico por imagem , Síndromes Neurotóxicas/etiologia , Receptores de Antígenos QuiméricosRESUMO
Viral breakthroughs (VB), defined as having detectable HCV VL while on anti-HCV therapy after achieving maximal suppression, have not yet been characterized with the use of PEG-IFN in HIV/HCV-coinfected patients. We evaluated possible mechanisms for VB among HIV/HCV-coinfected patients receiving PEG-IFN/RBV. Thirty HIV/HCV coinfected patients were treated with PEG-IFN (1.5 mug/kg sc qwk) and RBV (1-1.2 g daily) for 48 weeks. Liver chemistry, HCV VL, genotyping, DNA microarray, and sequencing of HCV E-2 envelope were performed before and during treatment. VB had lower baseline HCV VL but higher ALT and AST than relapsers (ETR) (p < 0.05) and lower CD4+ T lymphocytes (%) than patients with sustained virological responses (SVR), but similar first and second phase HCV viral kinetics (vs. ETR and SVR; p > 0.05). HCV genotypes and envelope sequences were similar for patients with VB pretreatment and at break-through. VB had higher levels of interferon-induced gene (IFIG) expression pretreatment than patients with ETR (p < 0.01). HIV/HCV-coinfected patients have a high rate of VB on PEG-IFN/RBV therapy characterized by higher levels of IFIG expression, immunodeficiency, and hepatic inflammation. Novel strategies are required for the treatment of persons with VB.
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Antivirais/uso terapêutico , Farmacorresistência Viral/imunologia , Infecções por HIV/complicações , Hepacivirus/efeitos dos fármacos , Hepatite C/imunologia , Hepatite C/virologia , Interferons/uso terapêutico , Adulto , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Contagem de Linfócito CD4 , Feminino , Infecções por HIV/imunologia , Hepacivirus/imunologia , Hepatite C/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Ribavirina/uso terapêutico , Carga ViralRESUMO
This prospective study was carried out during February 2000-April 2003 to characterize the relationship between the status of carotenoids, vitamin E, and retinol and anthropometric status in apparently healthy infants and their mothers in Blantyre, Malawi. Anthropometric status of infants and concentrations of carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, zeaxanthin, and lycopene), retinol, and alpha-tocopherol in plasma were measured in 173 infants at 12 months of age, and concentrations of carotenoids, retinol, and a-tocopherol in plasma were measured in their mothers two weeks postpartum. In multivariate analyses, concentrations of retinol, total carotenoids, non-provitamin A carotenoids, and alpha-tocopherol in infants were associated with under-weight (p = 0.05). Concentrations of a-tocopherol were associated with wasting (p = 0.04). Concentrations in mothers and infants were all correlated (correlation coefficients from 0.230 to 0.502, p < 0.003). The findings suggest that poor status of carotenoids, retinol, and alpha-tocopherol in infants is associated with their poor anthropometric status, and status of carotenoids, retinol, and alpha-tocopherol in mothers and infants has a low-to-moderate association in the mother-infant dyad.
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Antropometria/métodos , Carotenoides/sangue , Estado Nutricional/fisiologia , Vitamina A/sangue , Vitamina E/sangue , Adulto , Peso Corporal/fisiologia , Aleitamento Materno , Feminino , Humanos , Lactente , Fenômenos Fisiológicos da Nutrição do Lactente/fisiologia , Estudos Longitudinais , Malaui , Estudos Prospectivos , Síndrome de Emaciação/sangueRESUMO
Malaria is a leading cause of morbidity and mortality worldwide, and anemia is a common and sometimes serious complication of Plasmodium falciparum infection. Although micronutrient malnutrition is usually highly prevalent in malaria endemic areas, the contribution of micronutrient deficiencies to malarial anemia is often overlooked. Recent investigation suggests that micronutrients such as vitamin A, vitamin E, and zinc, may improve the morbidity of malaria through immune modulation and alteration of oxidative stress. Micronutrients are also involved in the pathogenesis of anemia and likely play a role in malarial anemia, but many clinical trials have not specifically addressed the impact of micronutrient supplementation on malarial anemia. Further work is needed to assess the effect of both clinic and community-based micronutrient interventions on malarial anemia in infants, children, and pregnant women.
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Anemia , Deficiência de Vitaminas/complicações , Malária Falciparum/complicações , Micronutrientes , Zinco/deficiência , Adolescente , Adulto , Anemia/epidemiologia , Anemia/etiologia , Anemia/mortalidade , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Micronutrientes/deficiência , Micronutrientes/uso terapêutico , Gravidez , PrevalênciaRESUMO
A clinic-based cohort study in Kampala, Uganda, was conducted to examine the relationship between severe malarial anaemia and plasma micronutrients. Plasma carotenoids, retinol, vitamin E, and four trace metal concentrations were measured at enrollment and seven days later in 273 children, aged 1-10 year(s), with acute, uncomplicated Plasmodium falciparum malaria. Concentrations of plasma provitamin A carotenoids (p < 0.0001), non-provitamin A carotenoids (p < 0.0001), retinol (p < 0.0001), all four trace elements (all p < 0.001), and vitamin E (p < 0.0001) rose significantly by day 7 among children without severe anaemia (haemoglobin 70 g/L). There was no change in provitamin A carotenoids (p = 0.24) among children with severe anaemia (haemoglobin <70 g/L), whereas non-provitaminAcarotenoids (p < 0.0001), retinol (p < 0.0001), and vitamin E (p = 0.011) increased. These observations also support the hypothesis that the use of provitamin A carotenoids increases during malaria infection.
Assuntos
Anemia/sangue , Anemia/parasitologia , Carotenoides/sangue , Malária Falciparum/sangue , Malária Falciparum/complicações , Plasmodium falciparum/parasitologia , Oligoelementos/sangue , Vitamina A/sangue , Vitamina E/sangue , Doença Aguda , Animais , Criança , Pré-Escolar , Estudos de Coortes , Humanos , Lactente , Malária Falciparum/parasitologia , Índice de Gravidade de Doença , UgandaRESUMO
OBJECTIVE: Diagnosing ventilator-associated pneumonia (VAP) is difficult, and misdiagnosis can lead to unnecessary and prolonged antibiotic treatment. We sought to quantify and characterize unjustified antimicrobial use for VAP and identify risk factors for continuation of antibiotics in patients without VAP after 3 days. METHODS: Patients suspected of having VAP were identified in 6 adult intensive care units (ICUs) over 1 year. A multidisciplinary adjudication committee determined whether the ICU team's VAP diagnosis and therapy were justified, using clinical, microbiologic, and radiographic data at diagnosis and on day 3. Outcomes included the proportion of VAP events misdiagnosed as and treated for VAP on days 1 and 3 and risk factors for the continuation of antibiotics in patients without VAP after day 3. RESULTS: Two hundred thirty-one events were identified as possible VAP by the ICUs. On day 1, 135 (58.4%) of them were determined to not have VAP by the committee. Antibiotics were continued for 120 (76%) of 158 events without VAP on day 3. After adjusting for acute physiology and chronic health evaluation II score and requiring vasopressors on day 1, sputum culture collection on day 3 was significantly associated with antibiotic continuation in patients without VAP. Patients without VAP or other infection received 1,183 excess days of antibiotics during the study. CONCLUSIONS: Overdiagnosis and treatment of VAP was common in this study and led to 1,183 excess days of antibiotics in patients with no indication for antibiotics. Clinical differences between non-VAP patients who had antibiotics continued or discontinued were minimal, suggesting that clinician preferences and behaviors contribute to unnecessary prescribing.
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Unidades de Terapia Intensiva/estatística & dados numéricos , Pneumonia Associada à Ventilação Mecânica/diagnóstico , Antibacterianos/uso terapêutico , Cuidados Críticos/estatística & dados numéricos , Erros de Diagnóstico/estatística & dados numéricos , Feminino , Humanos , Prescrição Inadequada/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Fatores de Risco , Fatores de TempoRESUMO
Community-acquired pneumonia (CAP) is one of the most common infectious diagnoses encountered in clinical practice and one of the leading causes of death in the United States. Adherence to antibiotic treatment guidelines is inconsistent and the erroneous diagnosis of CAP and misuse of antibiotics is prevalent in both inpatients and outpatients. This review summarizes interventions that may be promoted by antimicrobial stewardship programs to improve outcomes for patients with CAP.