RESUMEN
Background: COVID-19 began in December 2019, rapidly spreading worldwide. China implemented a dynamic zero-COVID strategy and strict control measures after the outbreak. However, Guangzhou city ended closed-off management by the end of November 2022, leading to exposure to SARS-CoV-2. Despite most hospitalized patients being infected or co-infected with SARS-CoV-2, some remained uninfected. We report two cases of bacterial pneumonia with elevated globulin levels not infected with SARS-CoV-2, aiming to identify protection factors of SARS-CoV-2 infection and provide a scientific basis for SARS-CoV-2 prevention. Case presentation: Case 1, a 92-year-old male, admitted on October 21, 2022, developed worsening cough and sputum after aspiration, diagnosed with bacterial pneumonia with Pseudomonas aeruginosa, Escherichia coli (CRE) and carbapenem-resistant Acinetobacter baumannii (CRAB) infections. He was treated with imipenem anti-infective therapy and mechanical ventilation, then switched to a combination of meropenem, voriconazole and amikacin anti-infective therapy due to recurrent infections and septic shock, and died of sepsis on 8 January 2023. Case 2 is an 82-year-old male admitted on 30 September 2022, with recurrent cough, sputum, and shortness of breath, diagnosed with bacterial pneumonia with carbapenem-resistant Klebsiella pneumoniae (CRKP) and Mycobacterium pneumoniae infections. He was treated with ventilator-assisted ventilation, meropenem, amikacin, tigecycline and mucomycin nebulization and discharged with improvement on 26 October. He was readmitted on 21 November 2022 and diagnosed with bacterial pneumonia. He was treated with cefoperazone sulbactam, amikacin, meropenem and fluconazole and discharged on 31 December. Neither patient was infected with SARS-CoV-2 during hospitalization. Notably, their globulin levels were elevated before SARS-CoV-2 exposure, gradually decreasing afterward. Conclusions: Patients with bacterial pneumonia with high globulin levels likely have large amounts of immunoglobulin, and that immunoglobulin cross-reactivity causes this protein to be involved in clearing SARS-CoV-2 and preventing infection. Therefore, bacterial pneumonia patients with high globulin levels included in this study were not infected with SARS-CoV-2. After exposure to SARS-CoV-2, the amount of globulin in the patient's body was reduced because it was used to clear SARS-CoV-2. The results of this study are expected to provide a theoretical basis for the study of the mechanism of prevention and treatment of SARS-CoV-2 infection.
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COVID-19 , Neumonía Bacteriana , SARS-CoV-2 , Humanos , Masculino , COVID-19/complicaciones , Neumonía Bacteriana/tratamiento farmacológico , Neumonía Bacteriana/diagnóstico , Anciano de 80 o más Años , Antibacterianos/uso terapéuticoRESUMEN
BACKGROUND: The 2016 IDSA guideline recommends a treatment duration of at least 7 days for hospital-acquired (HAP)/ventilator-associated pneumonia (VAP). The limited literature has demonstrated higher rates of recurrence for non-glucose fermenting gram-negative bacilli with short course therapy, raising the concern of optimal treatment duration for these pathogens. Therefore, we aimed to compare the outcomes for patients receiving shorter therapy treatment (≤ 8 days) versus longer regimen (> 8 days) for the treatment of multidrug resistant (MDR) Pseudomonas pneumonia. METHODS: A single-center, retrospective cohort study was conducted to evaluate adult patients receiving an antimicrobial regimen with activity against MDR Pseudomonas aeruginosa in respiratory culture between 2017 and 2020 for a minimum of 6 consecutive days. Exclusion criteria were inmates, those with polymicrobial pneumonia, community-acquired pneumonia, and infections requiring prolonged antibiotic therapy. RESULTS: Of 427 patients with MDR P. aeruginosa respiratory isolates, 85 patients were included. Baseline characteristics were similar among groups with a median age of 65.5 years and median APACHE 2 score of 20. Roughly 75% had ventilator-associated pneumonia. Compared to those who received ≤ 8 days of therapy, no difference was seen for clinical success in patients treated for more than 8 days (80% vs. 65.5%, p = 0.16). The number of 30-day and 90-day in-hospital mortality, 30-days relapse, and other secondary outcomes did not significantly differ among the treatment groups. CONCLUSIONS: Prolonging treatment duration beyond 8 days did not improve patient outcomes for MDR P. aeruginosa HAP/VAP.
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Antibacterianos , Farmacorresistencia Bacteriana Múltiple , Infecciones por Pseudomonas , Pseudomonas aeruginosa , Humanos , Masculino , Femenino , Pseudomonas aeruginosa/efectos de los fármacos , Estudios Retrospectivos , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Anciano , Persona de Mediana Edad , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/microbiología , Infecciones por Pseudomonas/mortalidad , Neumonía Asociada al Ventilador/tratamiento farmacológico , Neumonía Asociada al Ventilador/microbiología , Neumonía Asociada al Ventilador/mortalidad , Resultado del Tratamiento , Neumonía Bacteriana/tratamiento farmacológico , Neumonía Bacteriana/microbiología , Neumonía Bacteriana/mortalidad , Duración de la TerapiaRESUMEN
PURPOSE: Infection by carbapenem-resistant Klebsiella pneumoniae (CRKP) has high mortality. There is no clear optimal therapeutic choice for pneumonia caused by CRKP. The aim of this study was to compare the clinical outcomes and safety of the standard doses of polymyxin B-based regimens vs tigecycline-based regimens and to identify risk factors for mortality. METHODS: This retrospective cohort study included patients with pneumonia caused by CRKP between January 1, 2020 and December 31, 2022. The primary outcomes were 7-day bacterial eradication rate and 14- and 28-day all-cause mortality. The secondary outcome was incidence of acute kidney injury. RESULTS: Seventy-three patients were included in this study, 29 in the polymyxin B-based combination therapy group and 44 in tigecycline-based combination therapy group. There were no significant differences between the two groups in terms of the 7-day bacterial eradication rate (31.03% vs 20.45%, p = 0.409), the 14-day all-cause mortality (37.93% vs 22.73%, p = 0.160), and the incidence of acute kidney injury (14.29% vs 6.82%, p = 0.526). The 28-day all-cause mortality in the polymyxin B-based therapy group was higher than in the tigecycline-based group (75.86% vs 45.45%, p = 0.010). Binary logistic regression analysis revealed that male and previous use of carbapenems were independent factors associated with 28-day all-cause mortality for patients treated with polymyxin B (p < 0.05). CONCLUSIONS: Polymyxin B-based combination therapy at the standard dose should be used with caution for patients with CRKP-induced pneumonia, especially for men who used carbapenems prior to CRKP detection.
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Antibacterianos , Quimioterapia Combinada , Infecciones por Klebsiella , Klebsiella pneumoniae , Polimixina B , Tigeciclina , Humanos , Polimixina B/administración & dosificación , Polimixina B/uso terapéutico , Polimixina B/efectos adversos , Masculino , Estudios Retrospectivos , Tigeciclina/administración & dosificación , Tigeciclina/uso terapéutico , Tigeciclina/efectos adversos , Femenino , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Antibacterianos/uso terapéutico , Infecciones por Klebsiella/tratamiento farmacológico , Infecciones por Klebsiella/mortalidad , Infecciones por Klebsiella/epidemiología , Infecciones por Klebsiella/microbiología , Anciano , Klebsiella pneumoniae/efectos de los fármacos , Persona de Mediana Edad , Carbapenémicos/uso terapéutico , Carbapenémicos/efectos adversos , Carbapenémicos/administración & dosificación , Resultado del Tratamiento , Enterobacteriaceae Resistentes a los Carbapenémicos/efectos de los fármacos , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/epidemiología , Neumonía Bacteriana/tratamiento farmacológico , Neumonía Bacteriana/microbiología , Neumonía Bacteriana/mortalidadRESUMEN
Pseudomonas aeruginosa is a frequent cause of antimicrobial-resistant hospital-acquired pneumonia, especially in critically ill patients. Inflammation triggered by P. aeruginosa infection is necessary for bacterial clearance but must be spatially and temporally regulated to prevent further tissue damage and bacterial dissemination. Emerging data have shed light on the pro-resolving actions of angiotensin-(1-7) [Ang-(1-7)] signaling through the G protein-coupled receptor Mas (MasR) during infections. Herein, we investigated the role of the Ang-(1-7)/Mas axis in pneumonia caused by P. aeruginosa by using genetic and pharmacological approach and found that Mas receptor-deficient animals developed a more severe form of pneumonia showing higher neutrophilic infiltration into the airways, bacterial load, cytokines, and chemokines production and more severe pulmonary damage. Conversely, treatment of pseudomonas-infected mice with Ang-(1-7) was able to decrease neutrophilic infiltration in airways and lungs, local and systemic levels of pro-inflammatory cytokines and chemokines, and increase the efferocytosis rates, mitigating lung damage/dysfunction caused by infection. Notably, the therapeutic association of Ang-(1-7) with antibiotics improved the survival rates of mice subjected to lethal inoculum of P. aeruginosa, extending the therapeutic window for imipenem. Mechanistically, Ang-(1-7) increased phagocytosis of bacteria by neutrophils and macrophages to accelerate pathogen clearance. Altogether, harnessing the Ang-(1-7) pathway during infection is a potential strategy for the development of host-directed therapies to promote mechanisms of resistance and resilience to pneumonia.
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Angiotensina I , Antibacterianos , Ratones Endogámicos C57BL , Fragmentos de Péptidos , Proto-Oncogenes Mas , Infecciones por Pseudomonas , Pseudomonas aeruginosa , Receptores Acoplados a Proteínas G , Animales , Angiotensina I/metabolismo , Pseudomonas aeruginosa/efectos de los fármacos , Ratones , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/metabolismo , Infecciones por Pseudomonas/microbiología , Fragmentos de Péptidos/metabolismo , Fragmentos de Péptidos/farmacología , Receptores Acoplados a Proteínas G/metabolismo , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas/genética , Neumonía Bacteriana/tratamiento farmacológico , Neumonía Bacteriana/microbiología , Neumonía Bacteriana/patología , Neumonía Bacteriana/metabolismo , Citocinas/metabolismo , Ratones Noqueados , Neumonía/tratamiento farmacológico , Neumonía/metabolismo , Neumonía/microbiología , Masculino , Pulmón/microbiología , Pulmón/metabolismo , Pulmón/patología , Transducción de Señal/efectos de los fármacos , Infiltración Neutrófila/efectos de los fármacosRESUMEN
RATIONALE: Shewanella algae are Gram-negative bacteria that are widely found in aquatic habitats and rarely cause lung infections in inland areas. PATIENT CONCERNS: Cough with light-yellow phlegm for 2 weeks. DIAGNOSES: The final diagnosis was bacterial pneumonia. INTERVENTIONS: The patient was treated with ceftazidime (2 g, every 12 h) for 1 week. OUTCOMES: The patient's lung infection improved and he was discharged. LESSONS: This case highlights a rare occurrence of lung infection caused by Shewanella algae in elderly Tibetan men residing in non-marine environments.
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Antibacterianos , Infecciones por Bacterias Gramnegativas , Neumonía Bacteriana , Shewanella , Humanos , Masculino , Shewanella/aislamiento & purificación , Infecciones por Bacterias Gramnegativas/diagnóstico , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/microbiología , Neumonía Bacteriana/microbiología , Neumonía Bacteriana/tratamiento farmacológico , Neumonía Bacteriana/diagnóstico , Neumonía Bacteriana/complicaciones , Antibacterianos/uso terapéutico , Tibet , Ceftazidima/uso terapéutico , Ceftazidima/administración & dosificación , AncianoRESUMEN
SOURCE CITATION: Gohil SK, Septimus E, Kleinman K, et al. Stewardship prompts to improve antibiotic selection for pneumonia: the INSPIRE randomized clinical trial. JAMA. 2024;331:2007-2017. 38639729.
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Antibacterianos , Programas de Optimización del Uso de los Antimicrobianos , Humanos , Antibacterianos/uso terapéutico , Neumonía/tratamiento farmacológico , Sistemas de Entrada de Órdenes Médicas , Adulto , Neumonía Bacteriana/tratamiento farmacológicoRESUMEN
Carbapenem-resistant Acinetobacter baumannii (CRAB) pneumonia has been a serious problem in the intensive care unit (ICU). However, defined characteristics of respiratory microbiome in CRAB pneumonia are lacking nowadays. This study aimed to analyze respiratory microbiome of CRAB pneumonia compared to non-CRAB pneumonia and reveal the clinical significance of respiratory microbiome data in these patients. Patients diagnosed with severe pneumonia with mechanical ventilation were enrolled in the ICU of a tertiary care hospital. Respiratory specimens were collected on days 1, 4, 7, and 14 in each participant via tracheal aspiration. Clinical data and outcomes of each enrolled patient were collected via electronic medical records. Microbiome analysis was conducted with collected respiratory specimens undergone by next-generation sequencing of microbial 16S ribosomal DNA. Six CRAB pneumonia, 4 non-CRAB pneumonia and 5 healthy controls were enrolled. In CRAB pneumonia, CRAB was detected in 3 patients by sputum culture at day 1, while it was negative at day 1 and detected later in the others by follow-up sputum culture. Beta diversity plot analysis showed differences between each group. Shannon index was decreased markedly at day 4 in CRAB pneumonia compared to the others. Among CRAB pneumonia cases, 3 respiratory specimens were culture-negative, but positive by microbiome analysis. Lower respiratory microbiome in CRAB pneumonia had distinct characteristics and early loss of diversity compared to non-CRAB pneumonia, which might be related to poor clinical course. Moreover, CRAB acquisition and colonization would be predicted by preemptive microbiome analysis, which will contribute to effective infection control in the ICU.
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Infecciones por Acinetobacter , Acinetobacter baumannii , Carbapenémicos , Enfermedad Crítica , Microbiota , Humanos , Acinetobacter baumannii/aislamiento & purificación , Acinetobacter baumannii/efectos de los fármacos , Masculino , Carbapenémicos/farmacología , Carbapenémicos/uso terapéutico , Femenino , Persona de Mediana Edad , Infecciones por Acinetobacter/microbiología , Infecciones por Acinetobacter/tratamiento farmacológico , Microbiota/efectos de los fármacos , Anciano , Unidades de Cuidados Intensivos/estadística & datos numéricos , Neumonía Bacteriana/microbiología , Neumonía Bacteriana/tratamiento farmacológico , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Esputo/microbiología , Respiración Artificial/efectos adversosRESUMEN
Antimicrobial peptides (AMPs) possess strong antibacterial activity and low drug resistance, making them ideal candidates for bactericidal drugs for addressing the issue of traditional antibiotic resistance. In this study, a template (G(XXKK)nI, G = Gly; X = Leu, Ile, Phe, or Trp; n = 2, 3, or 4; K = Lys; I = Ile.) was employed for the devised of a variety of novel α-helical AMPs with a high therapeutic index. The AMP with the highest therapeutic index, WK2, was ultimately chosen following a thorough screening process. It demonstrates broad-spectrum and potent activity against both standard and multidrug-resistant bacteria, while also showing low hemolysis and rapid and efficient time-kill kinetics. Additionally, WK2 exhibits excellent efficacy in treating mouse models of Klebsiella pneumonia-induced lung infections and methicillin-resistant Staphylococcus aureus (MRSA)-induced skin wound infections while demonstrating good safety profiles in vivo. In conclusion, the template-based design methodology for novel AMPs with high therapeutic indices offers new insights into addressing antibiotic resistance problems. WK2 represents a promising antimicrobial agent.
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Antibacterianos , Péptidos Antimicrobianos , Klebsiella pneumoniae , Staphylococcus aureus Resistente a Meticilina , Pruebas de Sensibilidad Microbiana , Infección de Heridas , Animales , Ratones , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/uso terapéutico , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Klebsiella pneumoniae/efectos de los fármacos , Péptidos Antimicrobianos/farmacología , Péptidos Antimicrobianos/química , Péptidos Antimicrobianos/uso terapéutico , Neumonía Bacteriana/tratamiento farmacológico , Neumonía Bacteriana/microbiología , Infecciones por Klebsiella/tratamiento farmacológico , Infecciones por Klebsiella/microbiología , Femenino , Modelos Animales de Enfermedad , Humanos , Enfermedades Cutáneas Bacterianas/tratamiento farmacológico , Enfermedades Cutáneas Bacterianas/microbiologíaRESUMEN
CONTEXT: Pneumonia is a leading cause of death in young infants. OBJECTIVES: To evaluate the efficacy of different antibiotic regimens to treat young infant pneumonia on critical clinical outcomes. DATA SOURCES: MEDLINE, Embase, CINAHL, World Health Organization (WHO) Global Index Medicus, Cochrane Central Registry of Trials. STUDY SELECTION: We included randomized controlled trials of young infants aged 0 to 59 days with pneumonia (population) comparing the efficacy of antibiotic regimens (intervention) with alternate regimens or management (control) on clinical outcomes. DATA EXTRACTION: We extracted data and assessed risk of bias in duplicate. We used Grading of Recommendations, Assessment, Development, and Evaluation to assess certainty of evidence. LIMITATIONS: Trials were heterogeneous, which precluded data pooling. RESULTS: Of 2601 publications screened, 10 randomized controlled trials were included. Seven trials were hospital-based (n = 869) and 3 were nonhospital-based (n = 4329). No hospital-based trials evaluated WHO-recommended first-choice regimens. One trial found the WHO-recommended second-choice antibiotic, cefotaxime, to have similar rates of treatment success as non-WHO-recommended regimens of either amoxicillin-clavulanate (RR 0.99, 95% confidence interval 0.82-1.10) or amoxicillin-clavulanate/cefotaxime (RR 1.02, 95% confidence interval 0.86-1.12). Among 3 nonhospital-based trials comparing oral amoxicillin to alternate regimens to treat isolated tachypnea among infants aged 7-59 days, there were no differences in treatment failure between amoxicillin and alternate regimens. Certainty of evidence was low or very low for all primary outcomes. CONCLUSIONS: We found limited evidence to support the superiority of any single antibiotic regimen over alternate regimens to treat young infant pneumonia.
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Antibacterianos , Humanos , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Lactante , Recién Nacido , Ensayos Clínicos Controlados Aleatorios como Asunto , Neumonía/tratamiento farmacológico , Resultado del Tratamiento , Neumonía Bacteriana/tratamiento farmacológicoRESUMEN
BACKGROUND: Novel beta-lactams show activity against many multidrug-resistant Gram-negative bacteria that cause severe lung infections. Understanding pharmacokinetic/pharmacodynamic characteristics of these agents may help optimise outcomes in the treatment of pneumonia. OBJECTIVES: To describe and appraise studies that report pulmonary pharmacokinetic and pharmacodynamic data of cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, imipenem/cilastatin/relebactam and meropenem/vaborbactam. METHODS: MEDLINE (PubMed), Embase, Web of Science and Scopus libraries were used for the literature search. Pulmonary population pharmacokinetic and pharmacokinetic/pharmacodynamic studies on adult patients receiving cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, imipenem/cilastatin/relebactam, and meropenem/vaborbactam published in peer-reviewed journals were included. Two independent authors screened, reviewed and extracted data from included articles. A reporting guideline for clinical pharmacokinetic studies (ClinPK statement) was used for bias assessment. Relevant outcomes were included, such as population pharmacokinetic parameters and probability of target attainment of dosing regimens. RESULTS: Twenty-four articles were included. There was heterogeneity in study methods and reporting of results, with diversity across studies in adhering to the ClinPK statement checklist. Ceftolozane/tazobactam was the most studied agent. Only two studies collected epithelial lining fluid samples from patients with pneumonia. All the other phase I studies enrolled healthy subjects. Significant population heterogeneity was evident among available population pharmacokinetic models. Probabilities of target attainment rates above 90% using current licensed dosing regiments were reported in most studies. CONCLUSIONS: Although lung pharmacokinetics was rarely described, this review observed high target attainment using plasma pharmacokinetic data for all novel beta-lactams. Future studies should describe lung pharmacokinetics in patient populations at risk of carbapenem-resistant pathogen infections.
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Antibacterianos , Cefalosporinas , Combinación de Medicamentos , Bacterias Gramnegativas , Inhibidores de beta-Lactamasas , beta-Lactamas , Humanos , Inhibidores de beta-Lactamasas/farmacocinética , Inhibidores de beta-Lactamasas/uso terapéutico , Inhibidores de beta-Lactamasas/farmacología , Antibacterianos/farmacocinética , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , beta-Lactamas/farmacocinética , beta-Lactamas/uso terapéutico , beta-Lactamas/farmacología , Cefalosporinas/farmacocinética , Cefalosporinas/uso terapéutico , Cefalosporinas/farmacología , Bacterias Gramnegativas/efectos de los fármacos , Tazobactam/farmacocinética , Tazobactam/uso terapéutico , Tazobactam/farmacología , Neumonía Bacteriana/tratamiento farmacológico , Compuestos de Azabiciclo/farmacocinética , Compuestos de Azabiciclo/uso terapéutico , Compuestos de Azabiciclo/farmacología , Carbapenémicos/farmacocinética , Carbapenémicos/uso terapéutico , Carbapenémicos/farmacología , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Ceftazidima/farmacocinética , Ceftazidima/uso terapéutico , Cefiderocol , Meropenem/farmacocinética , Meropenem/uso terapéutico , Meropenem/farmacología , Imipenem/farmacocinética , Imipenem/uso terapéutico , Farmacorresistencia Bacteriana Múltiple , Pruebas de Sensibilidad Microbiana , Combinación Cilastatina e Imipenem/farmacocinética , Combinación Cilastatina e Imipenem/uso terapéutico , Ácidos Borónicos , Compuestos Heterocíclicos con 1 AnilloRESUMEN
OBJECTIVES: We evaluated the efficacies of human-simulated regimens (HSRs) of two clinically utilized sulbactam regimens: 1 g q6h 0.5 h infusion (maximum FDA-approved dosage) and 3 g q8h 4 h infusion (high-dose, prolonged-infusion regimen), against Acinetobacter baumannii in a translational murine model. METHODS: Thirty-two clinical A. baumannii isolates were investigated, of which 16 were sulbactam resistant (MICâ≥â16 mg/L), 6 were sulbactam intermediate (MICâ=â8 mg/L) and 10 were sulbactam susceptible (MICâ≤â4 mg/L). Efficacies of the two sulbactam HSRs were assessed in the neutropenic murine pneumonia model. Changes in log10 cfu/lungs at 24 h compared with 0 h controls were measured, and efficacy was defined as achieving 1 log kill relative to baseline. WGS of the isolates and bioinformatics analysis were performed to explore potential associations between the genomic backgrounds and the in vivo responses. RESULTS: Eleven isolates harboured blaOXA-23, of which 10 were sulbactam resistant, 1 was sulbactam intermediate while none was sulbactam susceptible. Both sulbactam HSRs achieved >1 log kill against sulbactam-susceptible isolates. Against sulbactam-intermediate and sulbactam-resistant isolates, lack of efficacy correlated with the presence of the blaOXA-23 gene; sulbactam 1 g HSR and 3 g HSR did not show efficacy against 11/11 and 9/11 blaOXA-23-positive isolates, respectively, while efficacy was observed against all 11 blaOXA-23-negative sulbactam-intermediate and sulbactam-resistant isolates (i.e. harbouring other resistance genes). CONCLUSIONS: A sulbactam high-dose prolonged-infusion regimen provides comparable activity to the standard dose against isolates currently considered sulbactam susceptible. However, the activity against isolates with intermediate and resistant susceptibility could be predicted by the detection of blaOXA-23. Enhancing detection capabilities of common diagnostic modalities to include OXA-23 can improve patient outcome.
Asunto(s)
Infecciones por Acinetobacter , Acinetobacter baumannii , Antibacterianos , Pruebas de Sensibilidad Microbiana , Sulbactam , beta-Lactamasas , Acinetobacter baumannii/efectos de los fármacos , Acinetobacter baumannii/genética , Sulbactam/administración & dosificación , Sulbactam/uso terapéutico , Sulbactam/farmacología , Infecciones por Acinetobacter/tratamiento farmacológico , Infecciones por Acinetobacter/microbiología , Animales , Antibacterianos/administración & dosificación , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Ratones , beta-Lactamasas/genética , Humanos , Neumonía Bacteriana/tratamiento farmacológico , Neumonía Bacteriana/microbiología , Modelos Animales de Enfermedad , Femenino , Resultado del Tratamiento , Farmacorresistencia BacterianaRESUMEN
BACKGROUND: Fosfomycin is gaining increasing attention for its activity against MDR or XDR pathogens. Currently, IV fosfomycin is a potential option for treating various infections, including urinary tract infections, pneumonia and skin infections when first-line treatments fail. OBJECTIVES: To evaluate the demographic, clinical, microbiological and treatment modality of children received IV fosfomycin to treat infections caused by MDR pathogens since there are few data on the use of fosfomycin in children. METHODS: This study was conducted retrospectively with patients under 18 years of age who were treated with IV fosfomycin for at least 72 h due to infections caused by MDR pathogens between January 2019 and October 2023 at Marmara University Pendik Training and Research Hospital, Istanbul, Türkiye. Data on demographic and clinical features, microbiological findings, treatment modalities and side effects were evaluated. RESULTS: Twenty-five children, for a total of 32 cases of infection episodes, with a mean age of 11.4â±â3.92 years who received IV fosfomycin were included. The most frequent comorbidity was chronic pulmonary diseases, and the most common infection needed for IV fosfomycin was MDR Pseudomonas aeruginosa pneumonia. In all cases, fosfomycin was administered in combination with other antibiotics, mainly meropenem-colistin (68.7%) or meropenem (15.6%). Twenty-two (71.9%) cases had favourable clinical responses at the end of therapy. CONCLUSIONS: Our results suggest that IV fosfomycin may be an effective treatment option for MDR pathogens in the paediatric population. Nevertheless, careful stewardship is necessary to maintain efficacy and reduce antimicrobial resistance selection risk.
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Antibacterianos , Farmacorresistencia Bacteriana Múltiple , Fosfomicina , Humanos , Fosfomicina/uso terapéutico , Estudios Retrospectivos , Niño , Femenino , Masculino , Antibacterianos/uso terapéutico , Adolescente , Preescolar , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/microbiología , Lactante , Neumonía Bacteriana/tratamiento farmacológico , Neumonía Bacteriana/microbiología , Turquía , Pruebas de Sensibilidad Microbiana , Neumonía/tratamiento farmacológico , Neumonía/microbiologíaRESUMEN
BACKGROUND: Sulbactam dosing for Acinetobacter baumannii infections has not been standardized due to limited available pharmacokinetics/pharmacodynamics (PK/PD) data. Herein, we report a comprehensive PK/PD analysis of ampicillin-sulbactam against A. baumannii pneumonia. METHODS: Twenty-one A. baumannii clinical isolates were tested in the neutropenic murine pneumonia model. For dose-ranging studies, groups of mice were administered escalating doses of ampicillin-sulbactam. Changes in log10cfu/lungs relative to 0 h were assessed. Dose-fractionation studies were performed. Estimates of the percentage of of time during which the unbound plasma sulbactam concentrations exceeded the MIC (%fTâ>âMIC) required for different efficacy endpoints were calculated. The probabilities of target attainment (PTA) for the 1-log kill plasma targets were estimated following clinically utilized sulbactam regimens. RESULTS: Dose-fractionation studies demonstrated time-dependent kill. Isolates resistant to both sulbactam and meropenem required three times the exposures to achieve 1-log kill; median [IQR] %fTâ>âMIC of 60.37% [51.6-66.8] compared with other phenotypes (21.17 [16.0-32.9] %fTâ>âMIC). Sulbactam standard dose (1 g q6h, 0.5 h infusion) provided >90% PTA up to MIC of 4 mg/L. Sulbactam 3 g q8h, 4 h inf provided greater PTA for isolates with sulbactam-intermediate susceptibility (8 mg/L, 100% versus 86% following the standard dose). Despite the higher exposure following 3 g q8h, 4 h inf, PTA was ≤57% among sulbactam-resistant/meropenem-resistant isolates. CONCLUSION: Sulbactam standard dose is a valuable regimen across sulbactam-susceptible isolates while the high-dose extended-infusion provides additional benefit against sulbactam-intermediate isolates. Given that most of the sulbactam-resistant A. baumannii isolates are meropenem-resistant, high-dose prolonged-infusion regimens are not expected to be effective as monotherapy against infections due to these isolates.
Asunto(s)
Infecciones por Acinetobacter , Acinetobacter baumannii , Ampicilina , Antibacterianos , Pruebas de Sensibilidad Microbiana , Sulbactam , Acinetobacter baumannii/efectos de los fármacos , Sulbactam/farmacocinética , Sulbactam/administración & dosificación , Sulbactam/farmacología , Sulbactam/uso terapéutico , Antibacterianos/farmacocinética , Antibacterianos/administración & dosificación , Antibacterianos/farmacología , Infecciones por Acinetobacter/tratamiento farmacológico , Infecciones por Acinetobacter/microbiología , Animales , Ampicilina/farmacocinética , Ampicilina/administración & dosificación , Ampicilina/farmacología , Ratones , Femenino , Modelos Animales de Enfermedad , Neumonía Bacteriana/tratamiento farmacológico , Neumonía Bacteriana/microbiología , HumanosRESUMEN
INTRODUCTION: The aim of this study was to compare the efficacy and safety of colistin sulfate (CS) with polymyxin B sulfate (PMB) in the treatment of pneumonia induced by carbapenem-resistant Gram-negative bacteria (CR-GNB). METHODOLOGY: Patients diagnosed with pneumonia caused by CR-GNB and admitted to the intensive care unit (ICU) from January 2020 to September 2022 were enrolled in this study. The patients were divided into the CS group and the PMB group according to their medication regimens. Group-wise demographic data, clinical efficacy, prognosis, and adverse events were analyzed and compared. RESULTS: A total of 120 patients (68 in the CS group and 52 in the PMB group) with pneumonia were included in the study. The majority of the pathogens were CR-Acinetobacter baumannii, followed by CR-Klebsiella pneumoniae, and CR-Pseudomonas aeruginosa. The clinical response rates in the CS and PMB groups after treatment were 62.0% and 65.4%, bacterial clearances were 44.0% and 36.5%, 28-day mortality rates were 16.0% and 13.5%, respectively; no significant differences between the two treatments were found. Nevertheless, the adverse effects were significantly less common in the CS group than in the PMB group, especially when treatments were administered intravenously. CONCLUSIONS: CS, a novel polymyxin E formulation, is as effective as PMB in treating pneumonia induced by CR-GNB while causing less side effects.
Asunto(s)
Antibacterianos , Colistina , Neumonía Bacteriana , Polimixina B , Humanos , Polimixina B/uso terapéutico , Polimixina B/administración & dosificación , Masculino , Colistina/uso terapéutico , Colistina/efectos adversos , Colistina/administración & dosificación , Femenino , Antibacterianos/uso terapéutico , Persona de Mediana Edad , Anciano , Neumonía Bacteriana/tratamiento farmacológico , Neumonía Bacteriana/microbiología , Estudios Retrospectivos , Acinetobacter baumannii/efectos de los fármacos , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Resultado del Tratamiento , Adulto , Bacterias Gramnegativas/efectos de los fármacos , Unidades de Cuidados Intensivos , Pseudomonas aeruginosa/efectos de los fármacos , Anciano de 80 o más Años , Klebsiella pneumoniae/efectos de los fármacosRESUMEN
Tropheryma whipplei is the causative agent of Whipple's disease, which is a rare multiorgan systemic disease. We report two cases of Tropheryma whipplei infection, all routine tests were negative and it was finally detected by mNGS. This may help clinicians increase awareness of the diagnosis and treatment of acute severe pneumonia and interstitial pneumonia caused by Tropheryma whipplei.
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Secuenciación de Nucleótidos de Alto Rendimiento , Metagenómica , Tropheryma , Enfermedad de Whipple , Humanos , Tropheryma/genética , Tropheryma/aislamiento & purificación , Enfermedad de Whipple/diagnóstico , Enfermedad de Whipple/tratamiento farmacológico , Enfermedad de Whipple/microbiología , Masculino , Metagenómica/métodos , Persona de Mediana Edad , Anciano , Femenino , Neumonía Bacteriana/microbiología , Neumonía Bacteriana/diagnóstico , Neumonía Bacteriana/tratamiento farmacológico , Antibacterianos/uso terapéuticoAsunto(s)
Burkholderia pseudomallei , Melioidosis , Sepsis , Humanos , Melioidosis/tratamiento farmacológico , Melioidosis/diagnóstico , Sepsis/microbiología , Sepsis/tratamiento farmacológico , Burkholderia pseudomallei/aislamiento & purificación , Masculino , Antibacterianos/uso terapéutico , Viaje , Neumonía Bacteriana/microbiología , Neumonía Bacteriana/tratamiento farmacológico , Persona de Mediana EdadRESUMEN
BACKGROUND: Metastatic brain abscesses caused by Klebsiella pneumoniae are extremely rare but life-threatening conditions. To depict a unique case of the middle-aged hypertensive man with an unusual presentation of metastatic brain abscesses originating from a pleural abscess caused by Klebsiella pneumoniae and subsequently leading to loss of consciousness (LOC). CASE REPORT: A 52-year-old Iranian man with a history of hypertension presented to the emergency department with a five-day history of worsening cough, high-grade fever, shortness of breath, chest pain, fatigue, and a productive cough. Laboratory tests revealed leukocytosis, elevated C-reactive protein, and respiratory alkalosis. A chest computed tomography scan confirmed pneumonia, and a brain scan revealed multiple hypodense lesions. Despite antibiotic therapy, the patient's condition worsened, leading to confusion, disorientation, and loss of consciousness. Magnetic resonance imaging revealed multiple ring-enhancing lesions, suggesting an abscess formation. Bronchial washings and BAL samples confirmed a lower respiratory tract infection. Cultures from the bronchial washings grew Klebsiella pneumoniae. CONCLUSIONS: Metastatic brain abscesses caused by Klebsiella pneumoniae are exceedingly rare but life-threatening conditions. Timely diagnosis and effective antimicrobial treatment are critical for patient outcomes. This case underscores the significance of recognizing atypical presentations of bacterial infections, as early detection and appropriate management can significantly impact patient outcomes.
Asunto(s)
Antibacterianos , Absceso Encefálico , Infecciones por Klebsiella , Klebsiella pneumoniae , Humanos , Masculino , Persona de Mediana Edad , Klebsiella pneumoniae/aislamiento & purificación , Infecciones por Klebsiella/diagnóstico , Infecciones por Klebsiella/tratamiento farmacológico , Infecciones por Klebsiella/microbiología , Absceso Encefálico/microbiología , Absceso Encefálico/tratamiento farmacológico , Absceso Encefálico/diagnóstico por imagen , Antibacterianos/uso terapéutico , Tomografía Computarizada por Rayos X , Imagen por Resonancia Magnética , Neumonía Bacteriana/microbiología , Neumonía Bacteriana/diagnóstico , Neumonía Bacteriana/tratamiento farmacológico , Neumonía Bacteriana/complicaciones , Inconsciencia/etiologíaRESUMEN
BACKGROUND: During autumn/winter 2022, UK pediatricians reported an unseasonal increase in invasive group A streptococcal infections; a striking proportion presenting with pneumonia with parapneumonic effusion. METHODS: Clinicians across the United Kingdom were requested to submit pseudonymized clinical data using a standardized report form for children (<16 years) admitted between September 30, 2022 and February 17, 2023, with microbiologically confirmed group A streptococcal pneumonia with parapneumonic effusion. RESULTS: From 185 cases submitted, the median patient age was 4.4 years, and 163 (88.1%) were previously healthy. Respiratory viral coinfection was detected on admission for 101/153 (66.0%) children using extended respiratory pathogen polymerase chain reaction panel. Molecular testing was the primary method of detecting group A streptococcus on pleural fluid (86/171; 50.3% samples). Primary surgical management was undertaken in 171 (92.4%) children; 153/171 (89.4%) had pleural drain inserted (96 with fibrinolytic agent), 14/171 (8.2%) had video-assisted thoracoscopic surgery. Fever duration after admission was prolonged (median, 12 days; interquartile range, 9-16). Intravenous antibiotic courses varied in length (median, 14 days; interquartile range, 12-21), with many children receiving multiple broad-spectrum antibiotics, although evidence for additional bacterial infection was limited. CONCLUSIONS: Most cases occurred with viral coinfection, a previously well-recognized risk with influenza and varicella zoster, highlighting the need to ensure routine vaccination coverage and progress on vaccines for other common viruses (eg, respiratory syncytial virus, human metapneumovirus) and for group A streptococcus. Molecular testing is valuable to detect viral coinfection and confirm invasive group A streptococcal diagnosis, expediting the incorporation of cases into national reporting systems. Range and duration of intravenous antibiotics administered demonstrated the need for research on the optimal duration of antimicrobials and improved stewardship.
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Derrame Pleural , Infecciones Estreptocócicas , Streptococcus pyogenes , Humanos , Preescolar , Infecciones Estreptocócicas/epidemiología , Infecciones Estreptocócicas/tratamiento farmacológico , Infecciones Estreptocócicas/microbiología , Masculino , Niño , Reino Unido/epidemiología , Femenino , Lactante , Derrame Pleural/microbiología , Derrame Pleural/epidemiología , Derrame Pleural/terapia , Streptococcus pyogenes/aislamiento & purificación , Antibacterianos/uso terapéutico , Coinfección/epidemiología , Coinfección/microbiología , Coinfección/virología , Coinfección/tratamiento farmacológico , Adolescente , Neumonía Bacteriana/epidemiología , Neumonía Bacteriana/microbiología , Neumonía Bacteriana/tratamiento farmacológicoRESUMEN
INTRODUCTION: Q fever, a zoonotic disease caused by Coxiella burnetii (C. burnetii), presents diagnostic challenges due to its clinical and radiological nonspecificity, which often mimics community-acquired pneumonia, coupled with the limitations of traditional diagnostic methods. Metagenomic next-generation sequencing (mNGS) has become an indispensable tool in clinical diagnostics for its high-throughput pathogen identification capabilities. Herein, we detail a case of acute Q fever pneumonia diagnosed with mNGS. CASE PRESENTATION: The patient exhibited symptoms of fever, cough, expectoration, and diarrhea for three days, with the pathogen undetected in initial laboratory assessments. Bronchoscopy and bronchoalveolar lavage (BAL) were conducted, leading to the identification of C. burnetii in the lavage fluid via mNGS. Consequently, the patient was promptly initiated on a treatment regimen of 100 mg doxycycline, administered orally every 12 hours. RESULTS: Post-treatment, the patient's temperature normalized, and a full recovery was observed. The follow-up chest CT scan revealed complete resolution of the right lower lobe consolidation. CONCLUSIONS: The clinical presentation of Q fever pneumonia lacks specificity, making diagnosis based solely on symptoms and imaging challenging. mNGS offers a superior alternative for identifying elusive or rarely cultured pathogens.
Asunto(s)
Coxiella burnetii , Secuenciación de Nucleótidos de Alto Rendimiento , Metagenómica , Fiebre Q , Humanos , Fiebre Q/diagnóstico , Fiebre Q/tratamiento farmacológico , Fiebre Q/microbiología , Coxiella burnetii/genética , Coxiella burnetii/aislamiento & purificación , Metagenómica/métodos , Masculino , Neumonía Bacteriana/diagnóstico , Neumonía Bacteriana/microbiología , Neumonía Bacteriana/tratamiento farmacológico , Antibacterianos/uso terapéutico , Doxiciclina/uso terapéutico , Líquido del Lavado Bronquioalveolar/microbiología , Persona de Mediana Edad , Tomografía Computarizada por Rayos XRESUMEN
Acinetobacter baumannii (Ab) is a well-known nosocomial pathogen that has emerged as a cause of community-acquired pneumonia (CAP) in tropical regions. Few global epidemiological studies of CAP-Ab have been published to date, and no data are available on this disease in France. We conducted a retrospective chart review of severe cases of CAP-Ab admitted to intensive care units in Réunion University Hospital between October 2014 and October 2022. Eight severe CAP-Ab cases were reviewed. Median patient age was 56.5 years. Sex ratio (male-to-female) was 3:1. Six cases (75.0%) occurred during the rainy season. Chronic alcohol use and smoking were found in 75.0% and 87.5% of cases, respectively. All patients presented in septic shock and with severe acute respiratory distress syndrome. Seven patients (87.5%) presented in cardiogenic shock, and renal replacement therapy was required for six patients (75.0%). Five cases (62.5%) presented with bacteremic pneumonia. The mortality rate was 62.5%. The median time from hospital admission to death was 3 days. All patients received inappropriate initial antibiotic therapy. Acinetobacter baumannii isolates were all susceptible to ceftazidime, cefepime, piperacillin-tazobactam, ciprofloxacin, gentamicin, and imipenem. Six isolates (75%) were also susceptible to ticarcillin, piperacillin, and cotrimoxazole. Severe CAP-Ab has a fulminant course and high mortality. A typical case is a middle-aged man with smoking and chronic alcohol use living in a tropical region and developing severe CAP during the rainy season. This clinical presentation should prompt administration of antibiotic therapy targeting Ab.