RESUMO
OBJECTIVES: Historically, patients with leukaemia and invasive fusariosis (IF) have experienced poor outcomes in the setting of persistent immunosuppression. Herein, we retrospectively reviewed the incidence, presentation and outcomes of IF that are scarcely studied in contemporary cohorts of leukaemia patients. METHODS: We identified adult leukaemia patients with proven or probable IF at MD Anderson Cancer Center during 2009-21. Independent risk factors for 42 day mortality after IF diagnosis were determined using a multivariable logistic regression model. Combined with historical data, the annual IF incidence density over the past 23 years was estimated using Poisson regression analysis. RESULTS: Among 140 leukaemia patients with IF (114 proven), 118 patients (84%) had relapsed/refractory leukaemia and 124 (89%) had neutropenia at IF diagnosis. One hundred patients (71%) had pulmonary IF, 88 (63%) had disseminated IF and 48 (34%) had fungaemia. Coinfections were common (55%). Eighty-nine patients (64%) had breakthrough IF to mould-active triazoles. Most patients (84%) received combination antifungal therapy. Neutrophil recovery [adjusted OR (aOR), 0.04; 95% CI, 0.01-0.14; Pâ<â0.0001], pulmonary IF (aOR, 3.28; 95% CI, 1.11-9.70; Pâ=â0.032) and high SOFA score (aOR, 1.91 per 1-point increase; 95% CI, 1.47-2.50; Pâ<â0.0001) were independent predictors of 42 day mortality outcomes. From 1998 to 2021, IF incidence density increased significantly at an annual ratio of 1.03 (95% CI, 1.01-1.06; Pâ=â0.04). CONCLUSIONS: IF is predominantly seen in patients with relapsed/refractory leukaemia and increasingly seen as a breakthrough infection to mould-active triazoles. Despite frequent combination antifungal therapy, high mortality rates have persisted in patients with lasting neutropenia.
Assuntos
Fusariose , Leucemia , Neutropenia , Adulto , Humanos , Fusariose/tratamento farmacológico , Fusariose/epidemiologia , Antifúngicos/uso terapêutico , Infecções Irruptivas , Azóis , Incidência , Estudos Retrospectivos , Triazóis , Fungos , Leucemia/complicações , Leucemia/epidemiologia , Leucemia/tratamento farmacológico , Neutropenia/complicações , Neutropenia/tratamento farmacológicoRESUMO
BACKGROUND: Non-typhoidal Salmonella (NTS) infection is thought to be more severe in cancer patients, but this has not been studied since the development of new cancer therapies, increasing antibiotic resistance and the introduction of new antibiotics. We sought to describe the demographic characteristics, microbiological findings, clinical manifestations, and outcomes of NTS infections in cancer patients at our institution. METHODS: We reviewed microbiology laboratory records and identified patients who had cancer and from whom NTS organisms were recovered between January 1, 2000 and December 31, 2013, at a comprehensive cancer center in Houston, Texas. Descriptive statistics were used to summarize patient characteristics, clinical presentation and outcomes. RESULTS: We identified 110 isolates from 82 patients with 88 episodes of NTS infection (including five relapses [6%] in four patients, and two consecutive episodes in one patient). Fifty-five patients (67%) had hematologic malignancies. Most NTS isolates were susceptible to the commonly prescribed antimicrobials. Sixty-nine percent of patients had sepsis and one-third had severe sepsis or septic shock. Gastroenteritis, bacteremia, or both were present in 69% of patients, and the rest had focal infection. Mortality at 30 days was low (8%). Relapses occurred only in patients receiving ≤ 10 days of antibiotic therapy. CONCLUSIONS: NTS affects predominantly patients with hematologic malignancies, followed by gastrointestinal and genitourinary cancers. Invasive disease, sepsis, and septic shock are common presentations among admitted patients. Antimicrobial prophylaxis may not prevent NTS infection. Thirty-day mortality and attributable mortality rates were low in our series compared to older case series. Early appropriate antibiotic therapy may have had a role in decreasing mortality. Relapses occurred in patients receiving ≤ 10 days of therapy, suggesting the need for longer duration of antibiotic therapy in cancer patients with uncomplicated NTS infections.
Assuntos
Bacteriemia , Infecções por Salmonella , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Bacteriemia/epidemiologia , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Salmonella , Infecções por Salmonella/tratamento farmacológico , Infecções por Salmonella/epidemiologiaRESUMO
Pharmacological immune checkpoint blockade has revolutionized oncological therapies, and its remarkable success has sparked interest in expanding checkpoint inhibitor therapy in infectious diseases. Herein, we evaluated the efficacy of programmed cell death protein 1 (PD-1) blockade in a murine invasive pulmonary aspergillosis model. We found that, compared with isotype-treated infected control mice, anti-PD-1-treated mice had improved survival, reduced fungal burden, increased lung concentrations of proinflammatory cytokines and neutrophil-attracting chemokines, and enhanced pulmonary leukocyte accumulation. Furthermore, combined treatment with anti-PD-1 and caspofungin resulted in a significant survival benefit compared with caspofungin or anti-PD-1 therapy alone, indicating a synergistic effect between PD-1 inhibitors and immunomodulatory antifungal agents.
Assuntos
Antifúngicos/farmacologia , Aspergillus/efeitos dos fármacos , Caspofungina/farmacologia , Inibidores de Checkpoint Imunológico/farmacologia , Aspergilose Pulmonar Invasiva/metabolismo , Aspergilose Pulmonar Invasiva/microbiologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Imuno-Histoquímica , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Camundongos , Testes de Sensibilidade Microbiana , Receptor de Morte Celular Programada 1/metabolismoRESUMO
BACKGROUND: BK polymavirus (BKPyV), a member of the family Polyomaviridae, is associated with increased morbidity and mortality in allogeneic stem cell transplant recipients. METHODS: In our previous retrospective study of 2477 stem cell transplant patients, BKPyV replication independently predicted chronic kidney disease and poor survival. In this study, using the same cohort, we derived and validated a risk grading system to identify patients at risk of BKPyV replication after transplantation in a user-friendly modality. We used 3 baseline variables (conditioning regimen, HLA match status, and underlying cancer diagnosis) that significantly predicted BKPyV replication in our initial study in a subdistribution hazard model with death as a competing risk. We also developed a nomogram of the hazard model as a visual aid. The AUC of the ROC of the risk-score-only model was 0.65. We further stratified the patients on the basis of risk score into low-, moderate-, and high-risk groups. RESULTS: The total risk score was significantly associated with BKPyV replication (P < .0001). At 30 days after transplantation, the low-risk (score ≤ 0) patients had a 9% chance of developing symptomatic BKPyV replication, while the high-risk (score ≥ 8) of the population had 56% of developing BKPyV replication. We validated the risk score using a separate cohort of 1478 patients. The AUC of the ROC of the risk-score-only model was 0.59. Both the total risk score and 3-level risk variable were significantly associated with BKPyV replication in this cohort (P < .0001). CONCLUSIONS: This grading system for the risk of symptomatic BKPyV replication may help in early monitoring and intervention to prevent BKPyV-associated morbidity, mortality, and kidney function decline.
Assuntos
Vírus BK , Transplante de Células-Tronco Hematopoéticas , Transplante de Rim , Infecções por Polyomavirus , Infecções Tumorais por Vírus , Humanos , Estudos Retrospectivos , Medição de Risco , Transplante de Células-Tronco , TransplantadosRESUMO
Infections with extended-spectrum-ß-lactamase (ESBL)-producing Escherichia coli are common in patients with hematologic malignancy. The utility of cefepime and piperacillin-tazobactam as empiric therapy for ESBL-producing E. coli bacteremia in patients with hematologic malignancy is largely unknown. We conducted a single-center, retrospective cohort review of 103 adult inpatients with leukemia and/or hematopoietic stem cell transplant (HCT) recipients with monomicrobial ESBL-producing E. coli bacteremia. No association between increased 14-day mortality and empiric treatment with cefepime (8%) or piperacillin-tazobactam (0%) relative to that with carbapenems (19%) was observed (P = 0.19 and P = 0.04, respectively). This observation was consistent in multivariate Cox proportional hazards models adjusted for confounding and an inverse probability of treatment-weighted (IPTW) Cox proportional hazards model. Both fever and persistent bacteremia were more common in patients treated empirically with cefepime or piperacillin-tazobactam. Empiric treatment with cefepime or piperacillin-tazobactam did not result in increased mortality relative to that with treatment with carbapenems in patients with hematologic malignancy and ESBL-producing E. coli bacteremia, although most patients were changed to carbapenems early in treatment. However, due to prolonged fever and persistent bacteremia, their role may be limited in this patient population.
Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Carbapenêmicos/uso terapêutico , Cefepima/uso terapêutico , Infecções por Escherichia coli/tratamento farmacológico , Combinação Piperacilina e Tazobactam/uso terapêutico , Adulto , Gestão de Antimicrobianos , Estudos de Coortes , Escherichia coli/efeitos dos fármacos , Escherichia coli/metabolismo , Infecções por Escherichia coli/mortalidade , Feminino , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , beta-Lactamases/metabolismoRESUMO
Cryptococcus neoformans is a saprophytic fungal pathogen that can cause serious illness in immune-compromised hosts and it presents with a wide variety of clinical symptoms. We present a fatal case of fulminant C. neoformans infection presenting as pericardial tamponade in a 71-year-old male with chronic myelomonocytic leukaemia undergoing chemotherapy with the JAK-STAT inhibitor ruxolitinib. We also review the published cases of fungal pericarditis/tamponade. In addition to illustrating an atypical presentation of C. neoformans, this case highlights the risk for opportunistic fungal infections in patients with haematological malignancies, especially the ones treated with small molecule kinase inhibitors.
Assuntos
Tamponamento Cardíaco/etiologia , Tamponamento Cardíaco/patologia , Criptococose/diagnóstico , Fatores Imunológicos/efeitos adversos , Leucemia Mielomonocítica Crônica/diagnóstico , Pericardite/diagnóstico , Pirazóis/efeitos adversos , Idoso , Criptococose/complicações , Criptococose/patologia , Evolução Fatal , Humanos , Fatores Imunológicos/administração & dosagem , Leucemia Mielomonocítica Crônica/complicações , Leucemia Mielomonocítica Crônica/tratamento farmacológico , Leucemia Mielomonocítica Crônica/patologia , Masculino , Nitrilas , Pericardite/complicações , Pericardite/patologia , Pirazóis/administração & dosagem , PirimidinasRESUMO
There is a paucity of data regarding mixed mold pulmonary infections (MMPIs) in patients with haematological malignancies with or without haematopoietic stem cell transplantation (HSCT). We retrospectively studied 27 such patients (2005-2015) and compared them to patients with invasive pulmonary aspergillosis (IPA) caused by Aspergillus fumigatus. Factors associated with the diagnosis of MMPIs were significant corticosteroid use [20 (74%) vs 6 (22%), P < 0.001], sputum as the source specimen [13 (48%) vs 3 (11%), P = 0.003], younger age (median age: 58 vs 66 years, P = 0.006), and male sex [22 (81%) vs 13 (48%), P = 0.01]. Haematological cancers other than acute myeloid leukaemia (AML)/myelodysplastic syndromes (MDS) were less common in MMPIs than in IPA patients [AML/MDS: 6 (22%) vs 14 (52%), P = 0.04]. Only significant corticosteroid use [95% CI (2.7-42.7), P < 0.001], and sputum as the source specimen [95% (1.6-41.6), P = 0.012] were statistically significant as independently associated with increased risk of MMPIs diagnosis in multivariate analysis. Total mortality rate at day 42 postdiagnosis was comparable in both groups.
Assuntos
Neoplasias Hematológicas/cirurgia , Aspergilose Pulmonar Invasiva/microbiologia , Complicações Pós-Operatórias/microbiologia , Adolescente , Adulto , Idoso , Aspergillus fumigatus/efeitos dos fármacos , Aspergillus fumigatus/genética , Aspergillus fumigatus/isolamento & purificação , Aspergillus fumigatus/fisiologia , Feminino , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/microbiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Aspergilose Pulmonar Invasiva/diagnóstico , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Aspergilose Pulmonar Invasiva/etiologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Atenção Terciária à Saúde/estatística & dados numéricos , Adulto JovemRESUMO
BACKGROUND: Azole-resistant aspergillosis in high-risk patients with hematological malignancy or hematopoietic stem cell transplantation (HSCT) is a cause of concern. METHODS: We examined changes over time in triazole minimum inhibitory concentrations (MICs) of 290 sequential Aspergillus isolates recovered from respiratory sources during 1999-2002 (before introduction of the Aspergillus-potent triazoles voriconazole and posaconazole) and 2003-2015 at MD Anderson Cancer Center. We also tested for polymorphisms in ergosterol biosynthetic genes (cyp51A, erg3C, erg1) in the 37 Aspergillus fumigatus isolates isolated from both periods that had non-wild-type (WT) MICs. For the 107 patients with hematologic cancer and/or HSCT with invasive pulmonary aspergillosis, we correlated in vitro susceptibility with 42-day mortality. RESULTS: Non-WT MICs were found in 37 (13%) isolates and was only low level (MIC <8 mg/L) in all isolates. Higher-triazole MICs were more frequent in the second period and were Aspergillus-species specific, and only encountered in A. fumigatus. No polymorphisms in cyp51A, erg3C, erg1 genes were identified. There was no correlation between in vitro MICs with 42-day mortality in patients with invasive pulmonary aspergillosis, irrespective of antifungal treatment. Asian race (odds ratio [OR], 20.9; 95% confidence interval [CI], 2.5-173.5; P = .005) and azole exposure in the prior 3 months (OR, 9.6; 95% CI, 1.9-48.5; P = .006) were associated with azole resistance. CONCLUSIONS: Non-WT azole MICs in Aspergillus are increasing and this is associated with prior azole exposure in patients with hematologic cancer or HSCT. However, no correlation of MIC with outcome of aspergillosis was found in our patient cohort.
Assuntos
Antifúngicos/farmacologia , Aspergillus/efeitos dos fármacos , Aspergilose Pulmonar Invasiva/microbiologia , Atenção Terciária à Saúde , Triazóis/farmacologia , Adulto , Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Aspergilose/microbiologia , Aspergillus/genética , Aspergillus/isolamento & purificação , Aspergillus fumigatus/efeitos dos fármacos , Estudos de Coortes , Sistema Enzimático do Citocromo P-450/genética , Farmacorresistência Fúngica/genética , Ergosterol/biossíntese , Feminino , Proteínas Fúngicas/genética , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/microbiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Aspergilose Pulmonar Invasiva/mortalidade , Masculino , Testes de Sensibilidade Microbiana , Polimorfismo Genético , Estudos Prospectivos , Resultado do Tratamento , Triazóis/uso terapêutico , Voriconazol/farmacologia , Voriconazol/uso terapêutico , Adulto JovemRESUMO
The 28-day crude mortality rate in 68 cancer patients with fluconazole-susceptible dose-dependent Candida glabrata fungemia started on treatment (within 48 h after blood culture collection) with an echinocandin or liposomal amphotericin-B was better (30%) than those treated with azole monotherapy (52%) (P = 0.07). After adjusting for confounders, azole monotherapy also was associated with worse 28-day survival (hazard ratio, 3.8; P = 0.003).
Assuntos
Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Azóis/uso terapêutico , Candida glabrata/efeitos dos fármacos , Candidemia/tratamento farmacológico , Equinocandinas/uso terapêutico , Fluconazol/uso terapêutico , Polienos/uso terapêutico , Candida glabrata/isolamento & purificação , Candidemia/microbiologia , Candidemia/mortalidade , Farmacorresistência Fúngica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Estudos RetrospectivosRESUMO
BACKGROUND: BK polyomavirus (BKPyV) infections are known indicators of immune suppression in hematopoietic stem cell transplant (HSCT) recipients; they can lead to hemorrhagic cystitis, ureteral stenosis, renal dysfunction, and prolonged hospital stays. In this study, we determined transplant-associated variables and immune parameters that can predict for the risk of BKPyV viruria. We hypothesized that BKPyV infection is a marker of poor immune recovery. METHODS: We analyzed all engrafted patients undergoing first allogeneic HSCT at MD Anderson Cancer Center in Houston between January 2004 and December 2012. We evaluated their immune parameters and their transplant-associated factors. BKPyV positivity was defined as BKPyV detection in urine by polymerase chain reaction testing. Cox proportional hazards model, as well as competing risk analysis method using subdistribution hazard models with death as competing risk, were applied to assess risk of BKPyV viruria. RESULTS: We identified a total of 2477 patients with a median age of 52 years. BKPyV viruria was manifest in 25% (n=629) of the patients. The median time from transplantation to BKPyV viruria development was 42 days among the patients who had BKPyV viruria. On multivariate analysis, tumor type, acute GVHD, chronic GVHD, myeloablative conditioning regimen, cord blood as the graft source, CD3+ , CD4+ , CD8+ , CD56+ , NK counts, and low platelet count were shown to be significantly associated with BKPyV infection. These finding were further confirmed when models incorporating the competing risk of death yielded similar findings. CONCLUSION: In this study, we report significant associations between BKPyV reactivation following allogeneic HSCT and suppressed immune variables. In addition, this study provides valuable information on the immune status of HSCT recipients as a predictor of BKPyV infections that may in turn help us formulate plans for more effective prevention and treatment of this infection.
Assuntos
Vírus BK/fisiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções por Polyomavirus/imunologia , Condicionamento Pré-Transplante/efeitos adversos , Infecções Tumorais por Vírus/imunologia , Doenças Urológicas/imunologia , Ativação Viral/imunologia , Vírus BK/isolamento & purificação , Feminino , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Agonistas Mieloablativos/efeitos adversos , Agonistas Mieloablativos/uso terapêutico , Infecções por Polyomavirus/urina , Infecções por Polyomavirus/virologia , Estudos Retrospectivos , Medição de Risco , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/efeitos adversos , Infecções Tumorais por Vírus/urina , Infecções Tumorais por Vírus/virologia , Doenças Urológicas/urina , Doenças Urológicas/virologiaRESUMO
The tracheoesophageal puncture (TEP) restores verbal communication after total laryngectomy using a one-way valved voice prosthesis (VP). Microbial colonization can shorten VP device life. Our aims were to investigate patterns of prosthetic and oral colonization, and record changes in VP device life after targeted decontamination. We conducted a retrospective review of TEP clinic patients who underwent microbial analysis of the VP between 01/2003 and 07/2013. Two subgroups were analyzed: (1) patients with microbial analysis of the VP and the mouth were analyzed to identify patterns of common contamination, and (2) patients who were prescribed targeted oral decontamination on the basis of the microbial analysis of the VP were analyzed to evaluate effects on device life. Among 42 patients, 3 patients had only fungal, 5 only bacterial, and 33 had polyspecies fungal and bacterial colonization. In the TEP-oral microflora subgroup (n = 15), 7 had common microorganisms in the mouth and on the VP. Among the decontamination subgroup (n = 23), 6 patients received broad spectrum rinse, 16 antifungal agents and 13 antibiotics, or a combination thereof. After targeted decontamination, the median device life of prostheses improved from 7.89 to 10.82 weeks (p = 0.260). The majority of patients with a suboptimal VP device life in this pilot had polyspecies bacterial and fungal colonization. VPs rarely had fungal contamination alone (3 %), and non-albicans fungal species were more common than expected. For these reasons, we are exploring the use of targeted decontamination regimens that were associated with 1.4-fold improvement in VP duration.
Assuntos
Biofilmes , Descontaminação , Neoplasias Laríngeas/cirurgia , Laringe Artificial/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/etiologia , Infecções Bacterianas/prevenção & controle , Feminino , Humanos , Laringectomia , Masculino , Pessoa de Meia-Idade , Implantação de Prótese , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/etiologia , Infecções Relacionadas à Prótese/prevenção & controle , Estudos RetrospectivosRESUMO
Resistance to the novel ß-lactam/ß-lactamase inhibitor combination ceftazidime-avibactam (CAZ-AVI) among carbapenem-resistant Enterobacteriaceae (CRE) has infrequently been reported in the United States. We report unexpectedly high rates of resistance to CAZ-AVI in CRE bloodstream isolates at our institution associated with the nonoutbreak spread of New Delhi metallo-ß-lactamase in diverse Enterobacteriaceae species.
Assuntos
Antibacterianos/uso terapêutico , Compostos Azabicíclicos/uso terapêutico , Bacteriemia , Ceftazidima/uso terapêutico , Infecções por Enterobacteriaceae , Enterobacteriaceae , Adulto , Idoso , Antibacterianos/farmacologia , Compostos Azabicíclicos/farmacologia , Bacteriemia/tratamento farmacológico , Bacteriemia/epidemiologia , Bacteriemia/microbiologia , Institutos de Câncer , Ceftazidima/farmacologia , Pré-Escolar , Combinação de Medicamentos , Farmacorresistência Bacteriana , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/enzimologia , Enterobacteriaceae/genética , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/epidemiologia , Infecções por Enterobacteriaceae/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , beta-LactamasesRESUMO
Development of therapy against infections caused by antibiotic-resistant pathogens is a major unmet need in contemporary medicine. In previous work, our group chemically modified an antimicrobial peptidomimetic motif for targeted applications against cancer and obesity. Here, we show that the modified motif per se is resistant to proteolytic degradation and is a candidate antiinfective agent. We also show that the susceptibility of microorganisms to the drug is independent of bacterial growth phase. Moreover, this peptidomimetic selectively interferes with the integrity and function of the microbial surface lipid bilayer, data indicative that bacterial death results from membrane disruption followed by dissipation of membrane potential. Finally, we demonstrate two potential translational applications: use against biofilms and synergy with antibiotics in use. In summary, we introduce the mechanism of action and the initial evaluation of a prototype drug and a platform for the development of D-enantiomer antimicrobial peptidomimetics that target bacterial membranes of certain gram-negative problem pathogens with promising translational applications.
Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Membrana Celular/metabolismo , Peptidomiméticos/química , Peptidomiméticos/farmacologia , Sequência de Aminoácidos , Bactérias/efeitos dos fármacos , Bactérias/crescimento & desenvolvimento , Bactérias/ultraestrutura , Biofilmes/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Membrana Celular/ultraestrutura , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Sinergismo Farmacológico , Quimioterapia Combinada , Cinética , Bicamadas Lipídicas/metabolismo , Testes de Sensibilidade Microbiana , Dados de Sequência Molecular , Fosfolipídeos/metabolismo , Estereoisomerismo , Fatores de TempoRESUMO
BACKGROUND: Herbaspirillum species are gram-negative Betaproteobacteria that inhabit the rhizosphere. We investigated a potential cluster of hospital-based Herbaspirillum species infections. METHODS: Cases were defined as Herbaspirillum species isolated from a patient in our comprehensive cancer center between 1 January 2006 and 15 October 2013. Case finding was performed by reviewing isolates initially identified as Burkholderia cepacia susceptible to all antibiotics tested, and 16S ribosomal DNA sequencing of available isolates to confirm their identity. Pulsed-field gel electrophoresis (PFGE) was performed to test genetic relatedness. Facility observations, infection prevention assessments, and environmental sampling were performed to investigate potential sources of Herbaspirillum species. RESULTS: Eight cases of Herbaspirillum species were identified. Isolates from the first 5 clustered cases were initially misidentified as B. cepacia, and available isolates from 4 of these cases were indistinguishable. The 3 subsequent cases were identified by prospective surveillance and had different PFGE patterns. All but 1 case-patient had bloodstream infections, and 6 presented with sepsis. Underlying diagnoses included solid tumors (3), leukemia (3), lymphoma (1), and aplastic anemia (1). Herbaspirillum species infections were hospital-onset in 5 patients and community-onset in 3. All symptomatic patients were treated with intravenous antibiotics, and their infections resolved. No environmental source or common mechanism of acquisition was identified. CONCLUSIONS: This is the first report of a hospital-based cluster of Herbaspirillum species infections. Herbaspirillum species are capable of causing bacteremia and sepsis in immunocompromised patients. Herbaspirillum species can be misidentified as Burkholderia cepacia by commercially available microbial identification systems.
Assuntos
Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Herbaspirillum/classificação , Herbaspirillum/isolamento & purificação , Neoplasias/complicações , Adolescente , Idoso , Betaproteobacteria , Burkholderia cepacia , Pré-Escolar , Análise por Conglomerados , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Eletroforese em Gel de Campo Pulsado , Feminino , Genótipo , Herbaspirillum/genética , Humanos , Masculino , Pessoa de Meia-Idade , Tipagem Molecular , RNA Ribossômico 16S/genética , Estudos Retrospectivos , Análise de Sequência de DNARESUMO
Many uncommon Candida species that cause bloodstream infections (BSIs) are not well-characterized. We investigated the epidemiology, antifungal use, susceptibility patterns, and factors associated with all-cause death among cancer patients in whom uncommon Candida spp. BSIs were diagnosed at a cancer treatment center during January 1998September 2013. Of 1,395 Candida bloodstream isolates, 79 from 68 patients were uncommon Candida spp. The incidence density of uncommon Candida spp. BSIs and their proportion to all candidemia episodes substantively increased during the study period, and the rise was associated with increasing use of echinocandin antifungal drugs. Thirty-seven patients had breakthrough infections during therapy or prophylaxis with various systemic antifungal drugs for >7 consecutive days; 21 were receiving an echinocandin. C. kefyr (82%), and C. lusitaniae (21%) isolates frequently showed caspofungin MICs above the epidemiologic cutoff values. These findings support the need for institutional surveillance for uncommon Candida spp. among cancer patients.
Assuntos
Candida/classificação , Candidemia/epidemiologia , Candidíase/epidemiologia , Neoplasias/microbiologia , Antifúngicos/uso terapêutico , Candidemia/classificação , Candidemia/microbiologia , Candidíase/classificação , Candidíase/microbiologia , Meios de Cultura , Educação Médica Continuada , Humanos , Incidência , Testes de Sensibilidade Microbiana/estatística & dados numéricos , Neoplasias/complicações , Neoplasias/epidemiologia , Neoplasias/imunologia , Fatores de Risco , Texas/epidemiologiaRESUMO
Four cases of central venous catheter-related Methylobacterium radiotolerans infection are presented here. The patients were all long-term catheter carriers with an underlying diagnosis of leukemia, and they mostly manifested fevers. The isolated bacterial strains all showed far better growth on buffered charcoal yeast extract agar during the initial isolation and/or subcultures than they did on sheep blood or chocolate agar. This microbiological feature may improve the culture recovery of this fastidious pink Gram-negative bacillus that has rarely been isolated in clinical microbiology laboratories.
Assuntos
Infecções Relacionadas a Cateter/microbiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Methylobacterium/isolamento & purificação , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Criança , Ciprofloxacina/uso terapêutico , Feminino , Humanos , Levofloxacino/uso terapêutico , Masculino , Pessoa de Meia-Idade , Ácido Penicilânico/análogos & derivados , Ácido Penicilânico/uso terapêutico , Piperacilina/uso terapêutico , Combinação Piperacilina e Tazobactam , Adulto JovemRESUMO
Legionella, a large group of environmental Gram-negative bacteria, represents an occasional cause of pneumonia. We analyzed the microbiological and clinical features of 33 consecutive cases of Legionella infections that occurred at the University of Texas MD Anderson Cancer Center, Houston, TX, from 2002 to 2014. The Legionella strains were isolated from bronchoscopy specimens (32 strains) and a blood culture (1 strain) and were identified by sequencing analysis of the full-length 16S rRNA gene. The 33 strains involved 12 Legionella species or subspecies: 15 strains of L. pneumophila subsp. pneumophila, 3 strains of L. pneumophila subsp. fraseri or L. pneumophila subsp. pascullei, 4 strains of "L. donaldsonii," 3 strains of L. micdadei, and one each of L. bozemanae, L. feeleii, L. gormanii, L. longbeachae, L. maceachernii, L. parisiensis, L. sainthelensi, and Legionella sp. strain D5382. All patients except one asymptomatic carrier showed pneumonia, including one with concurrent bacteremia. Nine patients died, with this infection being the immediate cause of death in six. Twenty-seven patients had underlying hematologic malignancies. Twenty-three patients were leukopenic. Six patients were recipients of allogeneic hematopoietic stem cell transplant, with their infections caused by five Legionella species. Together, these results suggest that diverse Legionella species infect patients with cancer in the Houston area and its vicinity. The five cases of pneumonia due to L. donaldsonii and Legionella sp. D5382 are likely the first reports of human infection with these organisms.
Assuntos
Variação Genética , Legionella/classificação , Legionella/genética , Legionelose/microbiologia , Legionelose/patologia , Neoplasias/complicações , Centros Médicos Acadêmicos , Adulto , Idoso , Análise por Conglomerados , DNA Ribossômico/química , DNA Ribossômico/genética , Feminino , Humanos , Legionella/isolamento & purificação , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Filogenia , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/patologia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Análise de Sobrevida , TexasRESUMO
BACKGROUND: Concern for serious infection due to ß-lactam-resistant viridans group streptococci (VGS) is a major factor driving empiric use of an anti-gram-positive antimicrobial in patients with febrile neutropenia. We sought to develop and validate a prediction model for the presence of ß-lactam resistance in VGS causing bloodstream infection (BSI) in neutropenic patients. METHODS: Data from 569 unique cases of VGS BSI in neutropenic patients from 2000 to 2010 at the MD Anderson Cancer Center were used to develop the clinical prediction model. Validation was done using 163 cases from 2011 to 2013. In vitro activity of ß-lactam agents was determined for 2011-2013 VGS bloodstream isolates. RESULTS: In vitro resistance to ß-lactam agents commonly used in the empiric treatment of febrile neutropenia was observed only for VGS isolates with a penicillin minimum inhibitory concentration (MIC) of ≥ 2 µg/mL. One hundred twenty-nine of 732 patients (17%) were infected with VGS strains with a penicillin MIC ≥ 2 µg/mL. For the derivation and validation cohorts, 98% of patients infected by VGS with a penicillin MIC of ≥ 2 µg/mL had at least 1 of the following risk factors: current use of a ß-lactam as antimicrobial prophylaxis, receipt of a ß-lactam antimicrobial in the previous 30 days, or nosocomial VGS BSI onset. Limiting empiric anti-gram-positive therapy to neutropenic patients having at least 1 of these 3 risk factors would have reduced such use by 42%. CONCLUSIONS: Simple clinical criteria can assist with targeting of anti-gram-positive therapy to febrile neutropenic patients at risk of serious ß-lactam-resistant VGS infection.
Assuntos
Bacteriemia/microbiologia , Técnicas de Apoio para a Decisão , Neoplasias/complicações , Neutropenia/complicações , Infecções Estreptocócicas/microbiologia , Estreptococos Viridans/efeitos dos fármacos , Resistência beta-Lactâmica , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Estreptococos Viridans/isolamento & purificaçãoRESUMO
Cancer patients are at risk for candidemia, and increasing Candida spp. resistance poses an emerging threat. We determined rates of antifungal drug resistance, identified factors associated with resistance, and investigated the correlation between resistance and all-cause mortality rates among cancer patients with ≥1 C. glabrata-positive blood culture at MD Anderson Cancer Center, Houston, Texas, USA, during March 2005-September 2013. Of 146 isolates, 30 (20.5%) were resistant to fluconazole, 15 (10.3%) to caspofungin, and 10 (6.8%) to multiple drugs (9 caspofungin-resistant isolates were also resistant to fluconazole, 1 to amphotericin B). Independently associated with fluconazole resistance were azole preexposure, hematologic malignancy, and mechanical ventilation. Independently associated with caspofungin resistance were echinocandin preexposure, monocytopenia, and total parenteral nutrition. Fluconazole resistance was highly associated with caspofungin resistance, independent of prior azole or echinocandin use. Caspofungin resistance was associated with increased 28-day all-cause mortality rates. These findings highlight the need for good stewardship of antifungal drugs.
Assuntos
Antifúngicos/farmacologia , Candida glabrata/efeitos dos fármacos , Candidíase/etiologia , Farmacorresistência Fúngica , Neoplasias/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Candida glabrata/isolamento & purificação , Candidíase/microbiologia , Candidíase/mortalidade , Causas de Morte , Criança , Farmacorresistência Fúngica Múltipla , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Fatores de Risco , Adulto JovemRESUMO
The response rate among 58 patients with cancer and candidemia or deep-seated candidiasis treated with micafungin monotherapy was 81%. Intensive care unit (ICU) stay, concomitant nonfungal infections, and acute kidney injury were significantly associated with the 30-day crude mortality rate. Severe neutropenia was an independent predictor of micafungin failure. The efficacy and safety of micafungin in cancer patients with invasive candidiasis were comparable to those reported for patients without malignancy and for cancer patients treated with caspofungin.