RESUMO
This is a retrospective single-center study of 24 patients who received ceftazidime-avibactam plus aztreonam (CZA/ATM) for the treatment of VIM-type-producing Gram-negative bacillus (GNB) infections. The bacteria isolated were Enterobacterales in 22 patients and Pseudomonas aeruginosa in 2. Sixteen out of 19 isolates showed synergistic activity. Two patients presented clinical failure at day 14, and the 30-day mortality was 17% (4/24). CZA/ATM could be considered an alternative therapy for VIM-type-producing GNB infections.
Assuntos
Aztreonam , beta-Lactamases , Humanos , Aztreonam/uso terapêutico , Estudos Retrospectivos , Testes de Sensibilidade Microbiana , Antibacterianos/uso terapêutico , Compostos Azabicíclicos/uso terapêutico , Ceftazidima/uso terapêutico , Bactérias Gram-Negativas , Combinação de MedicamentosRESUMO
PURPOSE: The aim of this study was to evaluate the effectiveness of ceftolozane/tazobactam (C/T) for treating extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) infections, and to analyze whether high C/T dosing (2 g ceftolozane and 1 g tazobactam every 8 h) and infection source control have an impact on outcome. METHODS: Retrospective study of all consecutive patients treated with C/T for XDR-PA infection at a tertiary referral hospital (November 2015-July 2017). Main clinical and microbiological variables were analyzed. RESULTS: Thirty-eight patients were included. Median age was 59.5 years and Charlson Comorbidity Index was 3.5. Fourteen (36.8%) patients had respiratory tract infection, six (15.8%) soft tissue, and six (15.8%) urinary tract infection. Twenty-three (60.5%) received high-dose C/T and in 24 (63.2%) C/T was combined with other antibiotics. At completion of treatment, 33 (86.8%) patients showed clinical response. At 90 days of follow-up, 26 (68.4%) achieved clinical cure, and 12 (31.6%) had clinical failure because of persistent infection in one patient, death attributable to the XDR-PA infection in four, and clinical recurrence in seven. All-cause mortality was 5 (13.2%). Lower C/T MIC and adequate infection source control were the only variables significantly associated with clinical cure. CONCLUSIONS: C/T should be considered for treating XDR-PA infections, with infection source control being an important factor to avoid failure and resistance.
Assuntos
Cefalosporinas/uso terapêutico , Farmacorresistência Bacteriana/efeitos dos fármacos , Ácido Penicilânico/análogos & derivados , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Cefalosporinas/farmacologia , Feminino , Seguimentos , Humanos , Controle de Infecções , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Ácido Penicilânico/farmacologia , Ácido Penicilânico/uso terapêutico , Infecções por Pseudomonas/diagnóstico , Pseudomonas aeruginosa/classificação , Pseudomonas aeruginosa/genética , Estudos Retrospectivos , Tazobactam , Falha de Tratamento , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: Describe secular trends in the epidemiology and outcome of Clostridium difficile infection (CDI) at a tertiary hospital. METHODS: All consecutive primary CDI episodes in adults (January 2006-December 2015) were included. CDI was diagnosed on the presence of diarrhoea and a positive stool test for C. difficile toxin A and/or B. To define trends, a time-series analysis was performed using yearly data on demographics, clinical characteristics, management, antimicrobial treatment, and outcome of CDI. Patients were followed-up for three months after the diagnosis. RESULTS: There were 724 CDI episodes. Over the period from 2006 to 2015, the incidence rose from 0.18 episodes/1000 admissions to 0.26 episodes (relative rate [RR] 1.43; 95%CI, 1.02-2.00; Pâ¯=â¯0.035). Median Charlson comorbidity index increased from 2 (IQR 1-3) to 4 (IQR 2-4) (RR 1.65; 95%CI, 1.12-2.41; Pâ¯=â¯0.005). Overall, 80.4% of patients received proton pump inhibitors (PPIs) prior to CDI, and the percentage of PPI discontinuations rose from 2.3% to 20.4% (RR 8.80; 95%CI 1.20-64.36; Pâ¯=â¯0.006). Management of non-Clostridium antibiotics also changed: antibiotic withdrawals or switches increased from 4.2% to 29.2% (RR 7.00; 95%CI 1.68-29.15, Pâ¯=â¯0.001). Regarding CDI treatment, the percentage of patients treated with metronidazole decreased (88.9% vs 52.6%) (RR 0.59 (0.48-0.73), Pâ¯<â¯0.001), whereas the percentage receiving vancomycin increased (1.9% vs 32.6%) (RR 17.62 (2.47-125.49), Pâ¯<â¯0.001). The percentages of cures, deaths, and first recurrences did not significantly change over the 10-year period. CONCLUSIONS: Changes in CDI management were associated with a stable prognosis (percentage of cures and first recurrences), even though affected patients had a greater number of comorbidities over time.
Assuntos
Clostridioides difficile/isolamento & purificação , Infecções por Clostridium/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Técnicas Bacteriológicas , Infecções por Clostridium/tratamento farmacológico , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Espanha/epidemiologia , Centros de Atenção Terciária , Resultado do Tratamento , Adulto JovemRESUMO
VIM-type-producing Gram-negative bacteria (GNB) infections are difficult to treat. This is a retrospective single-center study of 34 patients who received cefiderocol for the treatment of VIM-type-producing GNB infections, including 25 Pseudomonas spp., 7 Enterobacterales, and 5 Achromobacter sp. Primary outcomes were clinical failure (defined as death, lack of clinical improvement, or a switch to another drug) at day 14 and 30-day all-cause mortality. The median age was 59 years (IQR 53.7-73.4), and the median Charlson comorbidity index was 3.5 (IQR 2-5). The main infections were respiratory tract infections (n = 9, 27%) and skin and soft tissue infections (n = 9, 27%). Eight patients exhibited bacteremia. In 9/17 patients with a drainable focus, drainage was performed. The median cefiderocol treatment duration was 13 days (IQR 8-24). Five patients (15%) experienced clinical failure on day 14, and the thirty-day mortality rate was 9/34 (27%); two cases occurred because of an uncontrolled infection source, and one was due to a new infection caused by the same bacteria. The other six deaths were unrelated to the index infection. Five patients experienced microbiological recurrence within three months. Susceptibility testing revealed the development of cefiderocol resistance in 1/7 cases with persistent or recurrent positive cultures. Cefiderocol, even in monotherapy, could be considered for the treatment of VIM-type-producing GNB infections.
RESUMO
OBJECTIVES: Ablative electrocautery is effective treating anal high-grade squamous intraepithelial lesions (HSILs). However, persistence or recurrence of the HSIL despite ablative sessions is not uncommon. The aim of this study is to assess the feasibility of topical cidofovir as salvage therapy for the management of refractory HSIL. DESIGN: A prospective uncontrolled unicenter study of men and transgender people who have sex with men with HIV who had a refractory intra-anal HSIL after ablative treatments and who received topical cidofovir (ointment at 1%, auto-applicated, three times a week, a total of 8âweeks) as salvage therapy. Effectiveness was evaluated on-treatment defining response as resolution or regression to low-grade lesion of HSIL in the biopsy posttreatment. Tolerance and recurrences were recorded. RESULTS: From 2017 to 2022, 23 patients with refractory intra-anal HSIL (78.3% persistent lesions, 39% affecting > 50% of circumference, and a median of six previous ablative sessions) were treated with topical cidofovir. A response was observed in 16 of 23 patients [69.5% (95% confidence interval (95% CI) 50.8-88.4)]. Local tolerance was reported as regular or bad in 13 patients (52.2%), requiring modification of the treatment in eight patients (three early discontinuation and five dose reduction). Non-serious side effects were reported. After a median follow-up of 30.3âmonths, two of the 16 patients with a response developed recurrent HSIL [recurrence rate, 25.4% at 12âmonths (95% CI, 0-35)]. CONCLUSION: Topical cidofovir could be a good option in the management of anal HSIL due to its good effectiveness, low recurrence rate, and acceptable tolerance even in difficult-to-treat lesions.
Assuntos
Neoplasias do Ânus , Carcinoma in Situ , Infecções por HIV , Lesões Intraepiteliais Escamosas , Masculino , Humanos , Cidofovir/uso terapêutico , Estudos Prospectivos , Resultado do Tratamento , Neoplasias do Ânus/tratamento farmacológico , Neoplasias do Ânus/patologia , Homossexualidade MasculinaRESUMO
BACKGROUND: Recently, different therapeutic lines have been tried in the initial stage of the disease of COVID-19, including remdesivir and molnupiravir. There is scarce evidence on the efficacy and safety of molnupiravir in kidney transplant recipients (KTRs). METHODS: ingle-center prospective cohort study' all adult KTRs diagnosed with COVID-19 and treated with molnupiravir or remdesivir from January to April 2022 were included. RESULTS: Nine KTRs with SARS-CoV-2 (Omicron variant) infection and mild symptoms received molnupiravir in an outpatient basis and were compared with a cohort of similar patients treated with remdesivir (n = 7). Three patients in the molnupiravir cohort were in the early posttransplant period and received a basiliximab (n = 2) or antithymocite globulin-based induction (n = 1). One of the patients had been treated with methylprednisolone bolus and antithymocite globulin for an episode of acute rejection in the previous months. They were all vaccinated with mRNA vaccines' and all but 1 had serological response. Only one of the patients experienced clinical worsening despite molnupiravir treatment and developed pneumonia requiring hospital admission. None of the patients suffered adverse effects attributed to molnupiravir' and no adjustment of tacrolimus dose was needed. None of the patients treated with remdesivir progressed in COVID-19 severity. CONCLUSIONS: Our study suggests that KTRs with SARS-CoV-2 infection under treatment with molnupiravir have a good clinical evolution with a probable lower risk for hospitalization and no adverse effects. At the renal level, molnupiravir was well tolerated, with no evidence of nephrotoxicity secondary to the drug nor interactions with the immunosuppressive therapy.
Assuntos
Tratamento Farmacológico da COVID-19 , Transplante de Rim , Adulto , Humanos , SARS-CoV-2 , Basiliximab , Transplante de Rim/efeitos adversos , Tacrolimo/efeitos adversos , Rejeição de Enxerto/prevenção & controle , Estudos Prospectivos , Imunossupressores/efeitos adversos , Transplantados , MetilprednisolonaRESUMO
The progressive increase of infections produced by extensively drug-resistant carbapenemase-producing Klebsiella pneumoniae (XDR-CPKP) represents an important threat to public health. Unfortunately, optimal therapeutic options are scarce. Retrospective studies have recommended combined therapy with more than one antibiotic and, more recently, a double-carbapenem regimen has been reported to be an effective alternative therapy. Here, we describe an episode of sepsis in an immunocompromised patient after allogeneic hematopoietic stem cell transplantation, caused by an XDR-CPKP. Several in vitro synergy tests revealed a synergistic effect combining ertapenem and meropenem, which were used as combination therapy achieving clinical and microbiological success.
Assuntos
Antibacterianos/uso terapêutico , Hospedeiro Imunocomprometido , Infecções por Klebsiella/tratamento farmacológico , Sepse/tratamento farmacológico , Tienamicinas/uso terapêutico , beta-Lactamas/uso terapêutico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Combinação de Medicamentos , Ertapenem , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Infecções por Klebsiella/etiologia , Infecções por Klebsiella/imunologia , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae , Meropeném , Sarcoma Mieloide/imunologia , Sarcoma Mieloide/patologia , Sarcoma Mieloide/terapia , Sepse/etiologia , Sepse/imunologia , Sepse/microbiologia , Transplante Homólogo , Resultado do TratamentoAssuntos
Humanos , Masculino , Idoso , Voriconazol , Tansulosina , Interações Medicamentosas , Pacientes Internados , Exame Físico , Avaliação de Sintomas , Hipertensão , Dislipidemias , Síndrome de Leriche , Hiperuricemia , Doenças Transmissíveis , Microbiologia , Resultado do Tratamento , Anti-HipertensivosRESUMO
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