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1.
PLoS Pathog ; 18(2): e1010240, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35143595

RESUMO

Staphylococcus aureus bacteremia (SAB) remains a clinically challenging infection despite extensive investigation. Repurposing medications approved for other indications is appealing as clinical safety profiles have already been established. Ticagrelor, a reversible adenosine diphosphate receptor antagonist that prevents platelet aggregation, is indicated for patients suffering from acute coronary syndrome (ACS). However, some clinical data suggest that patients treated with ticagrelor are less likely to have poor outcomes due to S. aureus infection. There are several potential mechanisms by which ticagrelor may affect S. aureus virulence. These include direct antibacterial activity, up-regulation of the innate immune system through boosting platelet-mediated S. aureus killing, and prevention of S. aureus adhesion to host tissues. In this Pearl, we review the clinical data surrounding ticagrelor and infection as well as explore the evidence surrounding these proposed mechanisms of action. While more evidence is needed before antiplatelet medications formally become part of the arsenal against S. aureus infection, these potential mechanisms represent exciting pathways to target in the host/pathogen interface.


Assuntos
Bacteriemia/tratamento farmacológico , Plaquetas/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Ticagrelor/uso terapêutico , Interações Hospedeiro-Patógeno , Humanos , Imunidade Inata , Inibidores da Agregação Plaquetária/uso terapêutico , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/imunologia
2.
Transpl Infect Dis ; 25(6): e14113, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37594214

RESUMO

Recent advances in antimicrobial resistance detection have spurred the development of multiple assays that can accurately detect the presence of bacterial resistance from positive blood cultures, resulting in faster institution of effective antimicrobial therapy. Despite these advances, there are limited data regarding the use of these assays in solid organ transplant (SOT) recipients and there is little guidance on how to select, implement, and interpret them in clinical practice. We describe a practical approach to the implementation and interpretation of these assays in SOT recipients using the best available data and expert opinion. These findings were part of a consensus conference sponsored by the American Society of Transplantation held on December 7, 2021 and represent the collaboration between experts in transplant infectious diseases, pharmacy, antimicrobial and diagnostic stewardship, and clinical microbiology. Areas of unmet need and recommendations for future investigation are also presented.


Assuntos
Anti-Infecciosos , Doenças Transmissíveis , Transplante de Órgãos , Sepse , Humanos , Antibacterianos/uso terapêutico , Transplante de Órgãos/efeitos adversos , Transplante de Órgãos/métodos , Farmacorresistência Bacteriana , Anti-Infecciosos/uso terapêutico , Transplantados , Sepse/tratamento farmacológico
3.
Perfusion ; : 2676591231182249, 2023 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-37285484

RESUMO

INTRODUCTION: Varying rates of access site infections with temporary percutaneous cardiac devices have been reported in the literature. The purpose of this study is to determine the impact of a change in institutional practice in utilizing antimicrobial prophylaxis to prevent access site infections in patients with these devices. METHODS: This observational, pre-post implementation analysis evaluated the benefit of prophylactic antimicrobial therapy in adult patients with temporary percutaneous cardiac devices admitted to cardiac intensive care units. Patients in the pre-cohort received prophylactic antibiotics for the duration of device insertion. Patients in the post-cohort received a single dose of intravenous antibiotics for veno-arterial extracorporeal membrane oxygenation (VA-ECMO) or Impella® 5.5 device placement, and no antimicrobial prophylaxis for all other devices placed. The primary endpoint was the incidence of definitive access site infection. Secondary endpoints included the incidence of Clostridium difficile infection and initiation of broad-spectrum antibiotics. RESULTS: Fifty patients in the pre-cohort and 45 patients in the post-cohort were evaluated. Devices included intra-aortic balloon pumps, VA-ECMO, Impella® CP and Impella® 5.5. The median duration of device insertion was four days. No significant difference in the primary outcome was seen between the two groups. A significant reduction in prophylactic antimicrobial utilization and total days of antimicrobial exposure was observed in the post-implementation cohort. CONCLUSION: Based on the results of our study, the implemented guideline reduces the utilization of antimicrobial prophylaxis in patients with temporary percutaneous cardiac devices and does not result in an increased rate of infections.

4.
Eur J Clin Microbiol Infect Dis ; 40(12): 2627-2631, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33990891

RESUMO

Malakoplakia is a chronic granulomatous disease associated with incomplete clearance of bacterial pathogens. A multimodal approach to therapy includes antimicrobials with intracellular activity, reduction in immunosuppression, and debulking of lesions. Azithromycin has an intracellular mechanism of action and enhanced Gram-negative activity compared to other macrolides. Despite some in vitro data to support its use, there are no clinical breakpoints or epidemiological cut-off values for most Enterobacterales from the European Committee on Antimicrobial Susceptibility Testing (EUCAST) or the Clinical and Laboratory Standards Institute (CLSI). We present two cases, previously unreported, of Escherichia coli associated renal allograft malakoplakia successfully treated with azithromycin.


Assuntos
Aloenxertos/microbiologia , Antibacterianos/administração & dosagem , Azitromicina/administração & dosagem , Infecções por Escherichia coli/tratamento farmacológico , Transplante de Rim/efeitos adversos , Malacoplasia/tratamento farmacológico , Complicações Pós-Operatórias/tratamento farmacológico , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Escherichia coli/fisiologia , Infecções por Escherichia coli/microbiologia , Feminino , Humanos , Malacoplasia/etiologia , Malacoplasia/microbiologia , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/microbiologia
5.
Transpl Infect Dis ; 23(4): e13575, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33527677

RESUMO

Invasive candidiasis is one of the common infections in solid organ transplant recipients. Guidelines recommend echinocandins or liposomal amphotericin with consideration of flucytosine (5-fluorocytosine; 5-FC) as synergistic therapy for treatment of select deep-seated Candida infections, including complex endovascular infections. Flucytosine undergoes extensive renal elimination; however, optimal dosing in patients with renal impairment, or those requiring renal replacement therapy (RRT), is not well-established. We describe a case of a 60-year old female who underwent orthotopic heart transplant complicated by Candida parapsilosis complex fungemia with mediastinitis and development of end-stage renal disease requiring RRT. Flucytosine therapeutic drug monitoring was performed on continuous veno-venous hemofiltration (CVVH) and intermittent hemodialysis (iHD) to guide appropriate dosing. Our results support 5-FC doses of 25 mg/kg daily while undergoing CVVH with a low fluid replacement rate and 21 mg/kg post-iHD or 17 mg/kg daily while receiving thrice weekly iHD.


Assuntos
Injúria Renal Aguda , Terapia de Substituição Renal Contínua , Transplante de Coração , Hemofiltração , Injúria Renal Aguda/terapia , Monitoramento de Medicamentos , Feminino , Flucitosina/uso terapêutico , Transplante de Coração/efeitos adversos , Humanos , Pessoa de Meia-Idade , Diálise Renal/efeitos adversos
6.
J Emerg Med ; 58(2): 203-210, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32178960

RESUMO

BACKGROUND: Poor adherence to evidence-based guidelines and overuse of broad-spectrum antibiotics has been noted in the emergency department (ED). There is limited evidence on guideline-congruent empiric therapy for urinary tract infections (UTIs) and uropathogen susceptibilities in the ED observation unit (EDOU). OBJECTIVE: The primary objective was to evaluate the prescribing patterns for the empiric treatment of UTI in the EDOU. Secondary objectives were to analyze uropathogen susceptibilities in the EDOU and implement an algorithm for the empiric treatment of UTI. METHODS: This study retrospectively reviewed adult patients who received empiric UTI treatment in the EDOU from January 1, 2018 to April 1, 2018. Eligible patients were categorized as having either uncomplicated or complicated cystitis, or pyelonephritis based on their clinical diagnosis. Antimicrobial therapy was evaluated in accordance with national practice guidelines, institutional guidelines, and local antimicrobial susceptibility patterns. RESULTS: Patients with uncomplicated or complicated cystitis (n = 115) were provided guideline-congruent empiric treatment in 87% of cases. Patients with pyelonephritis (n = 35) were provided guideline-congruent empiric treatment in 57% of cases. Susceptibility patterns of uropathogens isolated from this patient sample differed slightly from the institutional antibiogram, notably depicting a lower Escherichia coli susceptibility rate. Fluoroquinolones were prescribed for a longer than recommended duration in 18 patients (60%). CONCLUSIONS: The majority of patients in this study were provided guideline-congruent empiric therapy. Nevertheless, there are opportunities to optimize empiric UTI treatment and improve antibiotic stewardship in the EDOU.


Assuntos
Antibacterianos/uso terapêutico , Gestão de Antimicrobianos , Unidades de Observação Clínica , Serviço Hospitalar de Emergência , Padrões de Prática Médica/estatística & dados numéricos , Infecções Urinárias/tratamento farmacológico , Centros Médicos Acadêmicos , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Feminino , Fidelidade a Diretrizes , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Retrospectivos , Infecções Urinárias/diagnóstico
7.
Transpl Infect Dis ; 21(2): e13048, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30636363

RESUMO

Invasive fungal infections are a common complication in immunocompromised patients, such as organ transplant recipients. Isavuconazole is a broad-spectrum azole antifungal for the treatment of aspergillosis and mucormycosis. The package insert for isavuconazole recommends against opening the capsule for administration through enteral feeding tubes. We describe the case of a 68-year-old man with a complex post-lung transplant course receiving isavuconazole for presumed invasive aspergillosis (bronchial alveolar lavage galactomannan index of >3.75) therapy administered through a gastrostomy-jejunostomy tube (G-J tube). Therapeutic drug monitoring was performed to ensure appropriate absorption. Peak and trough concentrations were measured in the early and late phases of the treatment course and resulted in trough levels of 2.7 mcg/mL and 4.0 mcg/mL, which is consistent with previously published trough concentrations of isavuconazole when the capsule was administered intact. This case report suggests that opening isavuconazole capsules and administration through a G-J tube results in appropriate absorption and serum drug levels comparable to intact capsules.


Assuntos
Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Infecções Fúngicas Invasivas/tratamento farmacológico , Nitrilas/administração & dosagem , Nitrilas/uso terapêutico , Piridinas/administração & dosagem , Piridinas/uso terapêutico , Triazóis/administração & dosagem , Triazóis/uso terapêutico , Idoso , Cápsulas/administração & dosagem , Monitoramento de Medicamentos , Nutrição Enteral/métodos , Humanos , Hospedeiro Imunocomprometido/efeitos dos fármacos , Jejuno/efeitos dos fármacos , Transplante de Pulmão/efeitos adversos , Masculino
11.
Pharmacotherapy ; 44(6): 435-443, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38840536

RESUMO

INTRODUCTION: Rezafungin is a second-generation, once-weekly echinocandin antifungal approved for the treatment of invasive candidiasis, including candidemia. In phase II/III studies of rezafungin versus caspofungin, patients with severe hepatic impairment were excluded due to lack of caspofungin data in this population. This open-label, single-dose, phase I study evaluated the pharmacokinetics (primary objective) and safety of rezafungin in subjects with moderate or severe hepatic impairment versus matched, healthy subjects with normal hepatic function. METHODS: Eight subjects each with moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment were matched 1:1 with healthy subjects for age, sex, and body mass index. Each subject received a single 400-mg, intravenous, 1-h infusion of rezafungin. Plasma pharmacokinetic sampling was performed at various time points through 336 h postdose. Pharmacokinetic parameters were derived by non-compartmental analysis. Safety was assessed throughout. RESULTS: All 32 subjects received study treatment and were included in all analyses. Despite overlapping distributions of total plasma concentrations, based on geometric least-squares (LS) mean ratios, the area under the plasma concentration-time curve from time zero (prior to the start of infusion) to infinity (AUC0-∞) was 32% lower in subjects with moderate (LS mean ratio, 67.55; 90% confidence interval [CI]: 53.91, 84.65) and severe (LS mean ratio, 67.84; 90% CI: 57.49, 80.05) hepatic impairment versus matched healthy subjects. The maximum plasma concentration (Cmax) was 12% lower in moderate hepatic impairment and 28% lower in severe hepatic impairment groups. Linear regression showed no significant trend in the degree of hepatic impairment (based on Child-Pugh score) on AUC0-∞ or Cmax (p > 0.05). Treatment-emergent adverse events were reported in seven subjects (21.9%; three subjects in each of the hepatic impairment groups, and one healthy subject), none of which were severe, serious, or resulted in withdrawal. CONCLUSIONS: Rezafungin is well tolerated and can be administered to patients with moderate or severe hepatic impairment without the need for dose adjustment. The modest reduction in exposures in subjects with hepatic impairment is not clinically meaningful and is unlikely to impact efficacy.


Assuntos
Antifúngicos , Equinocandinas , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Antifúngicos/farmacocinética , Antifúngicos/administração & dosagem , Antifúngicos/efeitos adversos , Equinocandinas/farmacocinética , Equinocandinas/efeitos adversos , Equinocandinas/administração & dosagem , Adulto , Idoso , Hepatopatias , Infusões Intravenosas , Área Sob a Curva , Índice de Gravidade de Doença , Estudos de Casos e Controles
12.
Antimicrob Agents Chemother ; 57(6): 2678-83, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23545527

RESUMO

Beta-lactams enhance the killing activity of vancomycin. Due to structural and mechanistic similarities between vancomycin and telavancin, we investigated the activity of telavancin combined with nafcillin and imipenem compared to the known synergistic combination of telavancin and gentamicin. Thirty strains of Staphylococcus aureus, 10 methicillin-susceptible S. aureus (MSSA), 10 methicillin-resistant S. aureus (MRSA), and 10 heterogeneously vancomycin-intermediate S. aureus (hVISA), were tested for synergy by time-kill methodology. Six strains (2 each of MSSA, MRSA, and hVISA) were further evaluated in an in vitro pharmacokinetic/pharmacodynamic (PK/PD) model with simulated regimens of 10 mg/kg of body weight of telavancin once daily alone and combined with 2 g nafcillin every 4 h, 500 mg imipenem every 6 h, or 5 mg/kg gentamicin once daily over 72 h. In the synergy test, 67% of strains displayed synergy with the combination of telavancin and gentamicin, 70% with telavancin and nafcillin, and 63% with telavancin and imipenem. In the PK/PD model, the activities of all three combinations against MRSA and hVISA were superior to all individual drugs alone (P ≤ 0.002) and were similar to each other (P ≥ 0.187). The activities of all three combinations against MSSA were generally similar to each other except for one strain where the combination of telavancin and imipenem was superior to all other regimens (P ≤ 0.011). The activity of the combination of telavancin and beta-lactam agents was similar to that of telavancin and gentamicin against S. aureus, including resistant strains. Because beta-lactam combinations are less likely to be nephrotoxic than telavancin plus gentamicin, these beta-lactam combinations may have clinical utility.


Assuntos
Aminoglicosídeos/farmacologia , Antibacterianos/farmacologia , Gentamicinas/farmacologia , Imipenem/farmacologia , Nafcilina/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Aminoglicosídeos/farmacocinética , Aminoglicosídeos/uso terapêutico , Antibacterianos/farmacocinética , Antibacterianos/uso terapêutico , Sinergismo Farmacológico , Quimioterapia Combinada , Gentamicinas/farmacocinética , Gentamicinas/uso terapêutico , Humanos , Imipenem/farmacocinética , Imipenem/uso terapêutico , Lipoglicopeptídeos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Modelos Biológicos , Nafcilina/farmacocinética , Nafcilina/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Resistência a Vancomicina/efeitos dos fármacos
13.
Ther Clin Risk Manag ; 18: 223-232, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35308097

RESUMO

Purpose of Review: Cytomegalovirus (CMV) infections are a common complication in solid organ (SOT) and hematopoietic stem cell transplant (HSCT) recipients, leading to increased morbidity and mortality. Currently available treatment options have reduced the burden of infection, but utilization of these agents can be limited by toxicities such as nephrotoxicity and/or myelosuppression as well as emergence of resistance. The expansion of our current armamentarium towards CMV infection is crucial. Here, we review an emerging therapy, maribavir, and the safety and efficacy of this potential new agent for the prophylaxis and treatment of CMV infections including resistant/refractory disease. Recent Findings: Maribavir is a novel agent with CMV activity approved by Federal Food and Drug Administration (FDA) in December 2021 for resistant/refractory disease. Compared to currently available treatment for CMV infection, maribavir has a unique mechanism of action, retains activity against most (val)ganciclovir resistant strains, provides a more predictable pharmacokinetic profile, and fewer severe toxicities. Maribavir has been studied in phase 2 and 3 studies with ongoing phase 3 studies. While maribavir failed to meet the primary endpoints in the initial phase 3 study for prophylaxis therapy in allogeneic-HSCT and liver transplant recipients, results from the phase 2 study when used for pre-emptive therapy after HSCT show similar efficacy to valganciclovir, and results from the phase 3 study examining resistant/refractory disease demonstrate superiority to investigator-initiated therapy of (val)ganciclovir, foscarnet, or cidofovir. Summary: Maribavir provides a new agent for the management of resistant/refractory CMV infection. Results of the recently published phase 3 study provide further insight into the role of this novel therapy.

14.
PLoS One ; 17(1): e0262342, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35025929

RESUMO

PURPOSE: Coronavirus disease-2019 (COVID-19) is associated with a wide spectrum of clinical symptoms including acute respiratory failure. Biomarkers that can predict outcomes in patients with COVID-19 can assist with patient management. The aim of this study is to evaluate whether procalcitonin (PCT) can predict clinical outcome and bacterial superinfection in patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). METHODS: Adult patients diagnosed with SARS-CoV-2 by nasopharyngeal PCR who were admitted to a tertiary care center in Boston, MA with SARS-CoV-2 infection between March 17 and April 30, 2020 with a baseline PCT value were studied. Patients who were presumed positive for SARS-CoV-2, who lacked PCT levels, or who had a positive urinalysis with negative cultures were excluded. Demographics, clinical and laboratory data were extracted from the electronic medical records. RESULTS: 324 patient charts were reviewed and grouped by clinical and microbiologic outcomes by day 28. Baseline PCT levels were significantly higher for patients who were treated for true bacteremia (p = 0.0005) and bacterial pneumonia (p = 0.00077) compared with the non-bacterial infection group. Baseline PCT positively correlated with the NIAID ordinal scale and survival over time. When compared to other inflammatory biomarkers, PCT showed superiority in predicting bacteremia. CONCLUSIONS: Baseline PCT levels are associated with outcome and bacterial superinfection in patients hospitalized with SARS-CoV-2.


Assuntos
Infecções Bacterianas/metabolismo , COVID-19/metabolismo , Pró-Calcitonina/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Boston , Estudos de Casos e Controles , Feminino , Humanos , Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2/patogenicidade
15.
Open Forum Infect Dis ; 8(2): ofab026, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33623807

RESUMO

BACKGROUND: Nephrotoxicity is a known adverse effect of polymyxin antibiotics, including colistin. Although previous meta-analyses have aimed to characterize colistin-associated nephrotoxicity risk relative to other antibiotics, included studies were observational in nature with high risk of confounding and heterogeneity. We conducted this systematic review and meta-analysis of exclusively randomized controlled trials (RCTs) to evaluate the incidence of nephrotoxicity associated with colistin versus minimally nephrotoxic antibiotics. METHODS: We searched PubMed, EMBASE, Cochrane Library, and 3 trial registries for RCTs comparing the nephrotoxicity of colistin to nonpolymyxin antibiotics. Randomized controlled trials that used aminoglycosides were excluded. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using random-effects models. The study outcome was the rate of nephrotoxicity. RESULTS: Five RCTs with a total of 377 patients were included. Most patients received colistin for pneumonia in the intensive care unit, and the comparators were ß-lactam-based regimens. Colistimethate sodium was dosed at 9 million units/day (300 mg/day of colistin base activity), with administration of a loading dose in 4 studies. The nephrotoxicity incidence in patients who received colistin was 36.2% (95% CI, 23.3% to 51.3%). The nephrotoxicity rate was significantly higher in the colistin arm than comparators (RR, 2.40; 95% CI, 1.47 to 3.91; P ≤ .001; I2 = 0%), and the number needed to harm was 5. Findings persisted upon one-study-removed-analysis. CONCLUSIONS: This meta-analysis of RCTs found a colistin-associated nephrotoxicity rate of 36.2% and an increase in this risk compared with ß-lactam-based regimens by 140%. Colistin should be regarded as a last-line agent and safer alternatives should be considered when possible.

16.
Ther Adv Infect Dis ; 8: 20499361211046669, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34589214

RESUMO

BACKGROUND: Remdesivir (RDV) was approved for treatment of coronavirus disease 2019 (COVID-19), in May 2020 under US Food and Drug Administration emergency use authorization (EUA). Clinical outcomes related to RDV use in hospitalized patients during the EUA period are not well described. METHODS: We conducted a retrospective study of patients who received RDV under EUA. The primary outcome was clinical recovery by day 14 as determined by an eight-category ordinal scale. Secondary outcomes included recovery and survival to day 28, and adverse events. Recovery and survival were calculated using a stratified log-rank Kaplan-Meier estimator and a Cox proportional hazards model. RESULTS: Overall, 164 patients received RDV between May and October 2020, and 153 (93.3%) had evaluable data. Most (77.1%) were hospitalized within 10 days of symptom onset, and 79.7% started RDV within 48 hours. By days 14 and 28, 96 (62.7%) and 117 patients (76.5%) met the definition of clinical recovery, respectively. Median time to recovery was 6 days [interquartile range (IQR) 4-12]. Mortality rates were 6.5% and 11.8% by days 14 and 28, respectively. Age and time to start of RDV after hospital admission were predictive of recovery and 28-day mortality. CONCLUSIONS: In this real-world experience, outcomes after 5 days of RDV therapy were comparable to those of clinical trials. Disease severity, age, and dexamethasone use influenced clinical outcomes. Time to RDV initiation appeared to affect recovery and 28-day mortality, a finding that should be explored further. Mortality rate decreased over the analysis period, which could be related to dexamethasone use and improved management of COVID-19.

17.
Open Forum Infect Dis ; 7(6): ofaa166, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32617367

RESUMO

Paecilomyces variotii is a ubiquitous environmental saprophyte with worldwide distribution. Commonly found in soil and decomposing organic material [1, 2], P. variotii can also be isolated from drinking water [3] and indoor and outdoor air [4-6]. In immunocompetent hosts, P. variotii has been reported as a cause of locally invasive disease including prosthetic valve endocarditis [7, 8], endophthalmitis [9, 10], rhinosinusitis [11, 12], and dialysis-associated peritonitis [13, 14]. In contrast, disseminated infections are more commonly reported in immunocompromised patients, including those with chronic granulomatous disease [15], solid malignancy [16], acute leukemia [17], lymphoma [18], multiple myeloma [19], and after stem cell transplant for myelodysplasia [20]. In 1 case series examining invasive infections by non-Aspergillus molds, P. variotii was the most common cause after Fusarium spp. [21]. Here, we present the case of an immunocompetent patient with extensive intravascular infection involving prosthetic material. We describe successful induction therapy with combination antifungals and extended suppression with posaconazole with clinical quiescence and eventual normalization of serum fungal biomarkers.

18.
World Allergy Organ J ; 13(1): 100093, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31921381

RESUMO

BACKGROUND: Facilitating beta-lactam antibiotic use in patients reporting beta-lactam allergies in acute care settings is important to individual patient outcomes and public health; however, few initiatives have targeted the Emergency Department (ED) setting. METHODS: We implemented pathways for patients reporting prior penicillin and/or cephalosporin hypersensitivity as part of a hospital guideline in the ED of a large academic medical center in the United States. We described beta-lactam test doses, pathway compliance, hypersensitivity reactions (HSRs), and allergy record updating associated with ED-administered beta-lactam test doses from October 2016 to June 2018. RESULTS: 310 beta-lactam antibiotic test doses were administered to patients with penicillin and/or cephalosporin allergy histories in the study period (average volume 15/month [standard deviation 4]). Test doses were to cephalosporins (85%), penicillins (12%), and carbapenems (4%). 219 (71%) of test doses were compliant with the pathways. Ten patients (3.2%; 95% CI 1.6%-5.9%) had HSRs; five HSR patients (50%) had beta-lactams administered that were not pathway compliant. The allergy record was updated in 146 (47%) of patients, with improvement over the study period (p < 0.001). CONCLUSIONS: Inpatient approaches to prescribing beta-lactams in patients reporting beta-lactam allergies can be operationalized in the ED. Additional efforts are required to ensure guideline compliance and appropriate allergy documentation.

19.
Infect Control Hosp Epidemiol ; 40(5): 528-535, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30915929

RESUMO

OBJECTIVE: To assess the safety of, and subsequent allergy documentation associated with, an antimicrobial stewardship intervention consisting of test-dose challenge procedures prompted by an electronic guideline for hospitalized patients with reported ß-lactam allergies. DESIGN: Retrospective cohort study. SETTING: Large healthcare system consisting of 2 academic and 3 community acute-care hospitals between April 2016 and December 2017. METHODS: We evaluated ß-lactam antibiotic test-dose outcomes, including adverse drug reactions (ADRs), hypersensitivity reactions (HSRs), and electronic health record (EHR) allergy record updates. HSR predictors were examined using a multivariable logistic regression model. Modification of the EHR allergy record after test doses considered relevant allergy entries added, deleted, and/or specified. RESULTS: We identified 1,046 test-doses: 809 (77%) to cephalosporins, 148 (14%) to penicillins, and 89 (9%) to carbapenems. Overall, 78 patients (7.5%; 95% confidence interval [CI], 5.9%-9.2%) had signs or symptoms of an ADR, and 40 (3.8%; 95% CI, 2.8%-5.2%) had confirmed HSRs. Most HSRs occurred at the second (ie, full-dose) step (68%) and required no treatment beyond drug discontinuation (58%); 3 HSR patients were treated with intramuscular epinephrine. Reported cephalosporin allergy history was associated with an increased odds of HSR (odds ratio [OR], 2.96; 95% CI, 1.34-6.58). Allergies were updated for 474 patients (45%), with records specified (82%), deleted (16%), and added (8%). CONCLUSION: This antimicrobial stewardship intervention using ß-lactam test-dose procedures was safe. Overall, 3.8% of patients with ß-lactam allergy histories had an HSR; cephalosporin allergy histories conferred a 3-fold increased risk. Encouraging EHR documentation might improve this safe, effective, and practical acute-care antibiotic stewardship tool.


Assuntos
Antibacterianos/efeitos adversos , Gestão de Antimicrobianos/métodos , Hipersensibilidade a Drogas/epidemiologia , beta-Lactamas/administração & dosagem , beta-Lactamas/efeitos adversos , Adulto , Idoso , Antibacterianos/administração & dosagem , Cefalosporinas/administração & dosagem , Cefalosporinas/efeitos adversos , Sistemas de Apoio a Decisões Clínicas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Humanos , Pacientes Internados , Masculino , Pessoa de Meia-Idade , Penicilinas/administração & dosagem , Penicilinas/efeitos adversos , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Estados Unidos/epidemiologia , Adulto Jovem
20.
J Allergy Clin Immunol Pract ; 5(3): 616-625.e7, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28483315

RESUMO

Addressing inaccurate penicillin allergies is encouraged as part of antibiotic stewardship in the inpatient setting. However, implementing interventions targeted at the 10% to 15% of inpatients reporting a previous penicillin allergy can pose substantial logistic challenges. We implemented a computerized guideline for patients with reported beta-lactam allergy at 5 hospitals within a single health care system in the Boston area. In this article, we describe our implementation roadmap, including both successes achieved and challenges faced. We explain key implementation steps, including assembling a team, stakeholder engagement, developing or selecting an approach, spreading the change, establishing measures, and measuring impact. The objective was to detail the lessons learned while empowering others to be part of this important, multidisciplinary work to improve the care of patients with reported beta-lactam allergies.


Assuntos
Hipersensibilidade a Drogas/diagnóstico , beta-Lactamas/efeitos adversos , Boston , Humanos , Pacientes Internados , Guias de Prática Clínica como Assunto , Testes Cutâneos , beta-Lactamas/uso terapêutico
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