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INTRODUCTION: Maribavir was recently approved by the FDA, expanding treatment options for post-solid-organ transplant refractory/resistant CMV. We sought to describe the post-marketing experience with maribavir at a large academic transplant center. METHODS: This was a retrospective observational study of all renal transplant recipients treated with maribavir for refractory/resistant CMV DNAemia/disease. CMV viral loads, immunosuppression regimens and management, resistance testing, and antiviral therapy durations were reviewed. Outcomes of interest included treatment success, defined as undetectable CMV DNAemia for two consecutive weeks or detected but unquantifiable DNAemia for five consecutive weeks, as well as the emergence of antiviral resistance, and recurrent DNAemia. RESULTS: From 2021 to 2023, 5/10 (50%) patients achieved durable virologic suppression with maribavir (classified as responders). Among responders, 2/5 (40%) experienced low-level CMV DNAemia recurrence (defined as a viral load less than 1000 IU/mL) within 8 weeks of antiviral discontinuation. Among nonresponders, 2/3 (66.7%) were found to have UL97 protein mutations associated with maribavir resistance identified 85 and 75 days after initiation of maribavir. Two patients are currently on maribavir with clinical outcomes that are yet to be determined. Responders had a mean reduction of 200 mg (SD-274 mg) in mycophenolate dosing with nonresponders having a mean increase of 167 mg (SD-764 mg). CONCLUSIONS: Maribavir, often in conjunction with mycophenolate dose reduction, was effective for many patients with refractory/resistant CMV DNAemia at our transplant center, though several experienced recurrent DNAemia. In patients who did not respond to therapy, resistance to maribavir was frequently detected. Clinicians treating these patients should remain vigilant for rebound CMV DNAemia and consider repeat antiviral resistance testing.
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Antivirais , Benzimidazóis , Infecções por Citomegalovirus , Citomegalovirus , Farmacorresistência Viral , Transplante de Rim , Ribonucleosídeos , Humanos , Estudos Retrospectivos , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/virologia , Citomegalovirus/genética , Citomegalovirus/efeitos dos fármacos , Masculino , Feminino , Antivirais/uso terapêutico , Pessoa de Meia-Idade , Ribonucleosídeos/uso terapêutico , Transplante de Rim/efeitos adversos , Seguimentos , Benzimidazóis/uso terapêutico , Prognóstico , Transplantados , Carga Viral , Adulto , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto/efeitos dos fármacos , Complicações Pós-Operatórias/tratamento farmacológico , Fatores de Risco , Idoso , Diclororribofuranosilbenzimidazol/análogos & derivadosRESUMO
Donor-derived infection is an uncommon but potentially devastating complication of solid organ transplantation (SOT). Accurate and timely identification of unexpected infectious disease transmission events has implications not only for the recipient(s) experiencing infection, but also other recipients of organs or tissues from the same donor who may require additional testing or risk mitigation, as well as the broader organ transplant regulatory framework. This narrative review synthesizes data from published reports of symptomatic unexpected donor-derived infections in SOT recipients to provide clinicians with a systematic approach to the evaluation of undifferentiated illnesses that may be of donor origin. Key reasons to consider donor-derived infection include certain microbiologically proven infections in the recipient, especially early after transplant, characteristics of the donor or their management that suggest potential exposure to or infection with specific pathogens prior to organ procurement, and select clinical syndromes that occur in the post-transplant period. Syndromes for which expedited consideration and evaluation of donor-derived infection may be warranted include central nervous system infection, graft or perigraft complications developing in the absence of typical risk factors, and unexplained critical illness/sepsis syndrome in the early post-transplant period. When embarking on an investigation of a suspected donor-derived infection, clinicians should apply knowledge of the entire continuum of the organ procurement and transplant process to ensure unbiased and comprehensive data collection that will facilitate appropriate adjudication of these uncommon but high-consequence events.
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Cytomegalovirus (CMV) infections are a major source of morbidity and mortality in solid organ transplant recipients. Prophylactic, preemptive, and hybrid prevention strategies have traditionally been the mainstay of CMV prevention but there is growing interest in the use of CMV cell-mediated immune assays to inform novel approaches to risk stratification. Recent evidence suggests that CMV interferon-gamma release assays can offer predictive insights into the risk for CMV-related illnesses, raising the potential for tailored CMV prevention strategies anchored to each individual's unique CMV immune profile. However, the predictive capacity of these assays for CMV-related illnesses can be profoundly influenced by when they are performed relative to transplant, and the induction immunosuppressive regimen the patient has received. In this review, we explore the relevant literature shaping our understanding of the optimal use of these assays. Furthermore, we also highlight the benefits of quantifying the CD4+ and CD8+ T-Cell responses to CMV, which is offered by some interferon-gamma release assays utilizing intracellular cytokine staining, for providing a holistic assessment of the recovery of cell-mediated immunity post-induction immunosuppression.
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Infecções por Citomegalovirus , Transplante de Órgãos , Humanos , Antivirais/uso terapêutico , Citomegalovirus , Infecções por Citomegalovirus/tratamento farmacológico , Linfócitos T CD8-Positivos , Transplantados , Transplante de Órgãos/efeitos adversosRESUMO
BACKGROUND: Cytomegalovirus (CMV) infection has broad implications for morbidity and mortality in renal transplant recipients (RTR). Routine surveillance for CMV replication with PCR-based quantitative nucleic acid testing (qNAT) assays is standard practice in most transplant centers, but the impact of assay sensitivity on antiviral decision-making and virologic outcomes has not been studied. We investigated the effects of an ultrasensitive CMV qNAT assay on multiple clinical outcomes, including time to detection and duration of CMV DNAemia. METHODS: We conducted a single-center cohort study contrasting RTRs monitored with a qNAT with a higher lower limit of quantification (LLOQ >300 IU/mL) with those monitored with a more sensitive qNAT (LLOQ >35 IU/mL). Patients were stratified by donor (D)/recipient (R) CMV serostatus (D+/R-: high risk; any R+: moderate risk). CMV viral load monitoring was performed monthly post transplantation, with the primary outcomes being time to CMV DNAemia and its duration. RESULTS: Total 1382 patients were analyzed from 2014 to 2016 and 2019 to 2021. Moderate-risk RTRs monitored with the more sensitive assay experienced a greater hazard for the development of a first episode of CMV DNAemia (aHR: 1.95, 95% confidence interval [CI]: 1.55-2.46) and an average of 24 (95% CI: 16.40-31.98) additional days of DNAemia. There was no difference in CMV end-organ disease or 1-year all-cause mortality between moderate-risk RTRs. CONCLUSIONS: The more sensitive assay was associated with earlier detection and extended durations of CMV DNAemia in moderate-risk RTRs, without altering clinical outcomes. These findings inform optimal use of these assays and antiviral stewardship in RTRs. KEY SUMMARY: The use of ultrasensitive CMV qNAT assays in moderate-risk CMV renal transplant recipients is associated with earlier detection and longer durations of CMV DNAemia without impacting CMV end-organ disease or 1-year mortality.
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Infecções por Citomegalovirus , Transplante de Rim , Humanos , Citomegalovirus/genética , Transplante de Rim/efeitos adversos , Estudos de Coortes , Estudos Retrospectivos , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/tratamento farmacológico , Transplantados , DNA Viral , Antivirais/uso terapêuticoRESUMO
Mutations accumulated by novel Severe Acute Respiratory Syndrome Coronavirus 2 Omicron sublineages contribute to evasion of previously effective monoclonal antibodies for treatment or prevention of Coronavirus Disease 2019 (COVID-19). Other authorized or approved antiviral drugs such as nirmatrelvir/ritonavir, remdesivir, and molnupiravir are, however, predicted to maintain activity against these sublineages and are key tools to reduce severe COVID-19 outcomes in vulnerable populations. A stepwise approach may be taken to target the appropriate antiviral drug to the appropriate patient, beginning with identifying whether a patient is at high risk for hospitalization or other complications of COVID-19. Among higher risk individuals, patient profile (including factors such as age, organ function, and comedications) and antiviral drug access inform suitable antiviral drug selection. When applied in targeted fashion, these therapies serve as a complement to vital ongoing nonpharmaceutical interventions and vaccination strategies that reduce morbidity and maximize protection against COVID-19.
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COVID-19 , SARS-CoV-2 , Humanos , Pacientes Ambulatoriais , Antivirais/uso terapêutico , Ritonavir/uso terapêutico , Tratamento Farmacológico da COVID-19RESUMO
BACKGROUND: Testing of vaccine candidates to prevent infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in an older population is important, since increased incidences of illness and death from coronavirus disease 2019 (Covid-19) have been associated with an older age. METHODS: We conducted a phase 1, dose-escalation, open-label trial of a messenger RNA vaccine, mRNA-1273, which encodes the stabilized prefusion SARS-CoV-2 spike protein (S-2P) in healthy adults. The trial was expanded to include 40 older adults, who were stratified according to age (56 to 70 years or ≥71 years). All the participants were assigned sequentially to receive two doses of either 25 µg or 100 µg of vaccine administered 28 days apart. RESULTS: Solicited adverse events were predominantly mild or moderate in severity and most frequently included fatigue, chills, headache, myalgia, and pain at the injection site. Such adverse events were dose-dependent and were more common after the second immunization. Binding-antibody responses increased rapidly after the first immunization. By day 57, among the participants who received the 25-µg dose, the anti-S-2P geometric mean titer (GMT) was 323,945 among those between the ages of 56 and 70 years and 1,128,391 among those who were 71 years of age or older; among the participants who received the 100-µg dose, the GMT in the two age subgroups was 1,183,066 and 3,638,522, respectively. After the second immunization, serum neutralizing activity was detected in all the participants by multiple methods. Binding- and neutralizing-antibody responses appeared to be similar to those previously reported among vaccine recipients between the ages of 18 and 55 years and were above the median of a panel of controls who had donated convalescent serum. The vaccine elicited a strong CD4 cytokine response involving type 1 helper T cells. CONCLUSIONS: In this small study involving older adults, adverse events associated with the mRNA-1273 vaccine were mainly mild or moderate. The 100-µg dose induced higher binding- and neutralizing-antibody titers than the 25-µg dose, which supports the use of the 100-µg dose in a phase 3 vaccine trial. (Funded by the National Institute of Allergy and Infectious Diseases and others; mRNA-1273 Study ClinicalTrials.gov number, NCT04283461.).
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Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , SARS-CoV-2/imunologia , Vacina de mRNA-1273 contra 2019-nCoV , Idoso , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Neutralização , Glicoproteína da Espícula de Coronavírus , Linfócitos T/fisiologiaRESUMO
Toxoplasma gondii can cause severe opportunistic infection in immunocompromised individuals, but diagnosis is often delayed. We conducted a retrospective review of solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients with toxoplasmosis between 2002 and 2018 at two large US academic transplant centers. Patients were identified by ICD-9 or ICD-10 toxoplasmosis codes, positive Toxoplasma polymerase chain reaction test result, or pathologic diagnosis. Data were collected regarding transplant type, time from transplant to toxoplasmosis diagnosis, clinical and radiographic features, and mortality at 30 and 90 days. Twenty patients were identified: 10 HSCT recipients (80% allogeneic HSCT) and 10 SOT recipients (60% deceased donor renal transplants). Rejection among SOT recipients (70%) and graft-versus-host disease (GVHD) prophylaxis among HSCT recipients (50%) were frequent. Median time from transplant to toxoplasmosis diagnosis was longer for SOT than HSCT (1385 vs. 5 days, P-value .002). Clinical manifestations most commonly were encephalitis (65%), respiratory failure (40%), renal failure (40%), and distributive shock (40%). Cohort 30-day mortality was 45%, and 90-day mortality was 55%. Diagnosis was postmortem in 25% of the cohort. Further evaluation of toxoplasmosis screening is needed for noncardiac SOT recipients, HSCT recipients with GVHD, and periods of increased net immunosuppression.
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Transplante de Células-Tronco Hematopoéticas , Toxoplasma , Toxoplasmose , Centros Médicos Acadêmicos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Estudos Retrospectivos , Toxoplasmose/diagnóstico , Toxoplasmose/epidemiologia , TransplantadosRESUMO
Adenovirus infection is commonly associated with self-limited respiratory and gastrointestinal illnesses. However, infection in immunocompromised individuals, such as transplant recipients, can cause severe life-threatening illness including pneumonitis, hemorrhagic cystitis, nephritis, hepatitis, and enterocolitis. In orthotopic liver transplant recipients, adenovirus viremia can cause hepatitis leading to marked transaminitis, allograft loss, and death. Although hepatic abscesses mediated by adenovirus have been described in other immunosuppressed patient populations, it has very rarely been described in liver transplant recipients. Here, we report two adult cases of hepatic abscesses following liver transplantation secondary to adenovirus infection and describe the successful treatment of these patients. Adenovirus should be considered as an uncommon etiology of hepatic abscess and unexplained fevers in adults following liver transplantation.
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Infecções por Adenoviridae , Abscesso Hepático , Transplante de Fígado , Adenoviridae , Infecções por Adenoviridae/complicações , Adulto , Febre , Humanos , Abscesso Hepático/etiologia , TransplantadosRESUMO
PURPOSE OF REVIEW: The use of durable ventricular assist devices (VAD) to manage end-stage heart failure is increasing, but infection remains a leading cause of morbidity and mortality among patients with VAD. In this review, we synthesize recent data pertaining to the epidemiology, diagnosis, management, and prevention of VAD infections, discuss transplant considerations in patients with VAD infections, and highlight remaining knowledge gaps. We also present a conceptual framework for treating clinicians to approach these infections that draws on the same principles that guide the treatment of analogous infections that occur in patients without VAD. RECENT FINDINGS: Despite advances in device design, surgical techniques, and preventative interventions, more than a third of VAD recipients still experience infection as an adverse outcome. Positron emission tomography has emerged as a promising modality for identifying and characterizing VAD infections. High-quality data to support many of the routine therapeutic strategies currently used for VAD infections-including suppressive antibiotic therapy, surgical debridement/device exchange, and novel antimicrobials for emerging multidrug-resistant organisms-remain limited. Although pre-transplant VAD infection may impact some early transplant outcomes, transplantation remains a viable option for patients with most types of VAD infection. Standardized definitions of VAD infection applied to large registry datasets have yielded key insights into the epidemiology of infectious complications among VAD recipients, but more prospective studies are needed to evaluate the effectiveness of existing and novel diagnostic and therapeutic strategies.
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Gerenciamento Clínico , Insuficiência Cardíaca/terapia , Coração Auxiliar , Guias de Prática Clínica como Assunto , Sistema de Registros , HumanosRESUMO
Preterm delivery is an important cause of perinatal morbidity and mortality, often precipitated by maternal infection or inflammation. Probiotic-containing foods, such as yogurt, may reduce systemic inflammatory responses. We sought to evaluate whether yogurt consumption during pregnancy is associated with decreased preterm delivery. We studied 965 women enrolled at midpregnancy into a clinical trial of prenatal docosahexaenoic acid supplementation in Mexico. Yogurt consumption during the previous 3 months was categorized as ≥5, 2-4, or <2 cups per week. Preterm delivery was defined as delivery of a live infant before 37 weeks gestation. We used logistic regression to evaluate the association between prenatal yogurt consumption and preterm delivery and examined interaction with maternal overweight status. In this population, 25.4%, 34.2%, and 40.4% of women reported consuming ≥5, 2-4, and <2 cups of yogurt per week, respectively. The prevalence of preterm delivery was 8.9%. Differences in preterm delivery were non-significant across maternal yogurt consumption groups; compared with women reporting <2 cups of yogurt per week, those reporting 2-4 cups of yogurt per week had adjusted odds ratio (aOR) for preterm delivery of 0.81 (95% confidence interval, CI [.46, 1.41]), and those reporting ≥5 cups of yogurt per week had aOR of 0.94 (95% CI [.51, 1.72]). The association between maternal yogurt consumption and preterm delivery differed significantly for nonoverweight women compared with overweight women (p for interaction = .01). Compared with nonoverweight women who consumed <2 cups of yogurt per week, nonoverweight women who consumed ≥5 cups of yogurt per week had aOR for preterm delivery of 0.24 (95% CI [.07, .89]). Among overweight women, there was no significant association. In this population, there was no overall association between prenatal yogurt consumption and preterm delivery. However, there was significant interaction with maternal overweight status; among nonoverweight women, higher prenatal yogurt consumption was associated with reduced preterm delivery.
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Dieta/métodos , Sobrepeso/epidemiologia , Complicações na Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Iogurte/estatística & dados numéricos , Adolescente , Adulto , Feminino , Humanos , México/epidemiologia , Gravidez , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: Statins have antiinflammatory effects that may impact vaccine-induced immune responses. We investigated the impact of statin therapy on influenza vaccine effectiveness (VE) against medically attended acute respiratory illness (MAARI). METHODS: We conducted a retrospective cohort study over nine influenza seasons using research databases of a large managed care organization in the United States. Influenza vaccination and statin prescription statuses of cohort members and MAARI cases were ascertained on a per-season basis. Incidence rate ratios (IRRs) of MAARI were estimated using Poisson regression and stratified by statin use. Using a ratio of ratios approach, we compared IRRs from periods during to IRRs from periods before influenza circulation and then used relative IRRs to compute VE. RESULTS: After adjustment for multiple prespecified covariates, the influenza VE against MAARI was lower among statin users than nonusers during periods of local (14.1% vs 22.9%; mean difference, 11.4%; 95% confidence interval [CI], -1.7% to 26.1%) and widespread (12.6% vs 26.2%; mean difference, 18.4%; 95% CI, 2.9%-36.2%) influenza circulation. CONCLUSIONS: In this study, statin therapy was associated with reduced influenza VE against MAARI. Since many cases of MAARI are not caused by influenza, studies of the impact of statins on influenza VE against laboratory-confirmed influenza are needed.
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Anti-Inflamatórios/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Infecções Respiratórias/imunologia , Doença Aguda , Idoso , Interações Medicamentosas , Feminino , Humanos , Influenza Humana/epidemiologia , Influenza Humana/imunologia , Masculino , Pessoa de Meia-Idade , Infecções Respiratórias/epidemiologia , Estudos RetrospectivosRESUMO
BACKGROUND: Acellular pertussis (aP) and whole-cell (wP) pertussis vaccines are presumed to have similar short-term (<3 years after completion of the primary series) efficacy. However, vaccine effect varies between individual pertussis vaccine formulations, and many originally studied formulations are now unavailable. An updated analysis of the short-term protective effect of pertussis vaccines limited to formulations currently on the market in developed countries is needed. METHODS: We conducted a systematic review and meta-analysis of published studies that evaluated pertussis vaccine efficacy or effectiveness within 3 years after completion (>3 doses) of a primary series of a currently available aP or wP vaccine formulation. The primary outcome was based on the World Health Organization (WHO) clinical case definitions for pertussis. Study quality was assessed using the approach developed by the Child Health Epidemiology Research Group. We determined overall effect sizes using random-effects meta-analyses, stratified by vaccine (aP or wP) and study (efficacy or effectiveness) type. RESULTS: Meta-analysis of 2 aP vaccine efficacy studies (assessing the 3-component GlaxoSmithKline and 5-component Sanofi-Pasteur formulations) yielded an overall aP vaccine efficacy of 84% (95% confidence interval [CI], 81%-87%). Meta-analysis of 3 wP vaccine effectiveness studies (assessing the Behringwerke, Pasteur/Mérieux, and SmithKline Beecham formulations) yielded an overall wP vaccine effectiveness of 94% (95% CI, 88%-97%) (bothI(2)= 0%). CONCLUSIONS: Although all contemporary aP and wP formulations protect against pertussis disease, in this meta-analysis the point estimate for short-term protective effect against WHO-defined pertussis in young children was lower for currently available aP vaccines than wP vaccines.
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Vacina contra Coqueluche , Coqueluche/prevenção & controle , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Resultado do Tratamento , Coqueluche/imunologiaRESUMO
BACKGROUND: Pertussis remains a cause of morbidity and mortality among young infants. There are limited data on the pertussis disease burden in this age group from low- and lower-middle-income countries, including in South Asia. METHODS: We conducted an active community-based surveillance study from February 2015 to April 2016 among 2 cohorts of young infants in 4 low-income settlements in Karachi, Pakistan. Infants were enrolled either at birth (closed cohort) or at ages up to 10 weeks (open cohort) and followed until 18 weeks of age. Nasopharyngeal swab specimens were obtained from infants who met a standardized syndromic case definition and tested for Bordetella pertussis using real-time polymerase chain reaction. We determined the incidence of pertussis using a protocol-defined case definition, as well as the US Centers for Disease Control and Prevention (CDC) definitions for confirmed and probable pertussis. RESULTS: Of 2021 infants enrolled into the study, 8 infants met the protocol-defined pertussis case definition, for an incidence of 3.96 (95% confidence interval [CI], 1.84-7.50) cases per 1000 infants. Seven of the pertussis cases met the CDC pertussis case definition (5 confirmed, 2 probable), for incidences of CDC-defined confirmed pertussis of 2.47 (95% CI, .90-5.48) cases per 1000 infants, and probable pertussis of 0.99 (95% CI, .17-3.27) cases per 1000 infants. Three of the pertussis cases were severe according to the Modified Preziosi Scale score. CONCLUSIONS: In one of the first prospective surveillance studies of infant pertussis in a developing country, we identified a moderate burden of pertussis disease in early infancy in Pakistan.
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Coqueluche/epidemiologia , Bordetella pertussis , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Paquistão/epidemiologia , Vigilância da População , Estudos Prospectivos , Estações do Ano , Índice de Gravidade de Doença , Fatores Socioeconômicos , Coqueluche/diagnósticoRESUMO
Mycobacterial infections resulting from cardiac implantable electronic devices are rare, but as more devices are implanted, these organisms are increasingly emerging as causes of early-onset infections. We report a patient with an implantable cardioverter-defibrillator pocket and associated bloodstream infection caused by an organism of the Mycobacterium fortuitum group, and we review the literature regarding mycobacterial infections resulting from cardiac device implantations. Thirty-two such infections have been previously described; most (70%) were caused by rapidly growing species, of which M. fortuitum group species were predominant.When managing such infections, clinicians should consider the potential need for extended incubation of routine cultures or dedicated mycobacterial cultures for accurate diagnosis; combination antimicrobial drug therapy, even for isolates that appear to be macrolide susceptible, because of the potential for inducible resistance to this drug class; and the arrhythmogenicity of the antimicrobial drugs traditionally recommended for infections caused by these organisms.
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Desfibriladores Implantáveis/efeitos adversos , Infecções por Mycobacterium não Tuberculosas/etiologia , Mycobacterium fortuitum , Antibacterianos/uso terapêutico , Procedimentos Cirúrgicos Cardiovasculares/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Próteses e Implantes/efeitos adversosRESUMO
Maternal influenza immunization can reduce influenza-attributable morbidity and mortality among pregnant women and infants who are too young to be vaccinated. Data from empirical studies also support the hypothesis that immunization can protect the fetus against adverse outcomes if the mother is exposed to influenza. In their theoretical analysis in the Journal, Hutcheon et al. (Am J Epidemiol 2016;184(3):227-232) critiqued the existing evidence of the fetal benefits of maternal influenza immunization by calculating the sample sizes needed to demonstrate hypothetical reductions in risk and concluded that the benefits observed in empirical studies are likely implausible. However, in their analysis, they did not take into account multiple fundamental characteristics of influenza epidemiology, including the time-variable effects of influenza illness and vaccination during pregnancy, or well-known differences in disease epidemiology between seasons, populations, and geographic regions. Although these and other factors might affect the magnitude of fetal benefit conferred by maternal influenza immunization, studies in which investigators have accounted for influenza circulation have demonstrated a consistent protective effect against a variety of adverse birth outcomes; those studies include the only randomized controlled trial designed a priori and adequately powered to do so. Only a comprehensive and nuanced assessment of the evidence base will allow for effective translation of these data into a global immunization policy.
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Influenza Humana/prevenção & controle , Vacinação , Feminino , Humanos , Imunização , GravidezRESUMO
IMPORTANCE: Parents hesitant to vaccinate their children may delay routine immunizations or seek exemptions from state vaccine mandates. Recent outbreaks of vaccine-preventable diseases in the United States have drawn attention to this phenomenon. Improved understanding of the association between vaccine refusal and the epidemiology of these diseases is needed. OBJECTIVE: To review the published literature to evaluate the association between vaccine delay, refusal, or exemption and the epidemiology of measles and pertussis, 2 vaccine-preventable diseases with recent US outbreaks. EVIDENCE REVIEW: Search of PubMed through November 30, 2015, for reports of US measles outbreaks that have occurred since measles was declared eliminated in the United States (after January 1, 2000), endemic and epidemic pertussis since the lowest point in US pertussis incidence (after January 1, 1977), and for studies that assessed disease risk in the context of vaccine delay or exemption. FINDINGS: We identified 18 published measles studies (9 annual summaries and 9 outbreak reports), which described 1416 measles cases (individual age range, 2 weeks-84 years; 178 cases younger than 12 months) and more than half (56.8%) had no history of measles vaccination. Of the 970 measles cases with detailed vaccination data, 574 cases were unvaccinated despite being vaccine eligible and 405 (70.6%) of these had nonmedical exemptions (eg, exemptions for religious or philosophical reasons, as opposed to medical contraindications; 41.8% of total). Among 32 reports of pertussis outbreaks, which included 10,609 individuals for whom vaccination status was reported (age range, 10 days-87 years), the 5 largest statewide epidemics had substantial proportions (range, 24%-45%) of unvaccinated or undervaccinated individuals. However, several pertussis outbreaks also occurred in highly vaccinated populations, indicating waning immunity. Nine reports (describing 12 outbreaks) provided detailed vaccination data on unimmunized cases; among 8 of these outbreaks from 59% through 93% of unvaccinated individuals were intentionally unvaccinated. CONCLUSIONS AND RELEVANCE: A substantial proportion of the US measles cases in the era after elimination were intentionally unvaccinated. The phenomenon of vaccine refusal was associated with an increased risk for measles among people who refuse vaccines and among fully vaccinated individuals. Although pertussis resurgence has been attributed to waning immunity and other factors, vaccine refusal was still associated with an increased risk for pertussis in some populations.
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Surtos de Doenças/estatística & dados numéricos , Sarampo/epidemiologia , Recusa do Paciente ao Tratamento/estatística & dados numéricos , Vacinação , Coqueluche/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Sarampo/prevenção & controle , Vacina contra Sarampo/administração & dosagem , Pessoa de Meia-Idade , Vacina contra Coqueluche/administração & dosagem , Estados Unidos/epidemiologia , Coqueluche/prevenção & controleRESUMO
A 46-year-old man with HIV infection and active intravenous drug use presented with approximately two weeks of fevers and body aches. On physical examination he was somnolent, had a new systolic murmur, bilateral conjunctival hemorrhages, diffuse petechiae, and left-sided arm weakness. Echocardiography revealed a large mitral valve vegetation and brain imaging demonstrated numerous embolic infarctions. Blood cultures grew Serratia marcescens. Despite aggressive treatment with meropenem the patient died due to intracranial hemorrhage complicated by herniation. Serratia marcescens is an uncommon cause of infective endocarditis. While this disease has historically been associated with intravenous drug use, more recent reports suggest that it is now largely a consequence of opportunistic infections of the chronically ill. Our case highlights several characteristic features of this infection, including isolation of a non-pigmented strain of the organism, an antibiotic susceptibility profile suggestive of AmpC ß-lactamase production, and rapid clinical deterioration with multiple embolic complications resulting in death. In this review we discuss the history, epidemiology, and management of endovascular infections due to Serratia spp., emphasizing the continued importance of considering this organism in the differential diagnosis of endocarditis among intravenous drug users and as a potential indication for surgical therapy.