RESUMO
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.
Assuntos
Angiotensina I , Antibacterianos , Camundongos Endogâmicos C57BL , Fragmentos de Peptídeos , Proto-Oncogene Mas , Infecções por Pseudomonas , Pseudomonas aeruginosa , Receptores Acoplados a Proteínas G , Animais , Angiotensina I/metabolismo , Pseudomonas aeruginosa/efeitos dos fármacos , Camundongos , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/metabolismo , Infecções por Pseudomonas/microbiologia , Fragmentos de Peptídeos/metabolismo , Fragmentos de Peptídeos/farmacologia , Receptores Acoplados a Proteínas G/metabolismo , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas/genética , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/patologia , Pneumonia Bacteriana/metabolismo , Citocinas/metabolismo , Camundongos Knockout , Pneumonia/tratamento farmacológico , Pneumonia/metabolismo , Pneumonia/microbiologia , Masculino , Pulmão/microbiologia , Pulmão/metabolismo , Pulmão/patologia , Transdução de Sinais/efeitos dos fármacos , Infiltração de Neutrófilos/efeitos dos fármacosRESUMO
Sodium houttuyfonate (SH), derived from the widely utilized natural herb Houttuynia cordata, exhibits an effective therapeutic effect on various diseases, including bacterial and fungal infections, especially the respiratory tract infection. Therefore, the anti-microbial mechanisms of SH may be different from the single-target action mechanism of conventional antibiotics, and further research is needed to clarify this. Firstly, we discovered that SH can effectively intervene in mouse lung infections by reducing bacterial load and acute inflammation response related to pneumonia caused by Pseudomonas aeruginosa. Interestingly, our results confirmed that SH has surface activity and can directly induce changes in the cell wall the shedding of surface lipopolysaccharide (LPS). Additionally, we found that SH-induced shedding of LPS can induce M1 polarization of macrophages in the early stage, leading to the production of corresponding polarization effector molecules. Subsequently, we discovered that SH-induced M1 polarization cells can effectively phagocytose and kill bacterial cells. The protein expression results indicated that SH can enhance the expression of M1 polarization pathway of TLR4/MyD88/NF-κB during the initial phase of macrophage and pathogen interaction. In summary, our results imply that SH could directly induce the shedding of P. aeruginosa LPS in a surfactant-like manner. Afterwards, the SH induced abscisic LPS can initiate the TLR4/MyD88/NF-κB immune pathway to trigger the M1 polarization of macrophages, which might intervene the P. aeruginosa-caused acute lung infection at early stage. Based on these findings, we attempted to coin the term "immune feedback eradication mechanism against pathogen of natural product" to describe this potent antimicrobial mechanism of SH.
Assuntos
Lipopolissacarídeos , Macrófagos , Pseudomonas aeruginosa , Sulfitos , Animais , Lipopolissacarídeos/farmacologia , Camundongos , Pseudomonas aeruginosa/efeitos dos fármacos , Sulfitos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/imunologia , Macrófagos/microbiologia , Receptor 4 Toll-Like/metabolismo , Infecções por Pseudomonas/imunologia , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Alcanos/farmacologia , Células RAW 264.7 , Camundongos Endogâmicos C57BL , Pneumonia Bacteriana/imunologia , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/tratamento farmacológico , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Fagocitose/efeitos dos fármacos , Antibacterianos/farmacologia , Transdução de Sinais/efeitos dos fármacosRESUMO
INTRODUCTION: Nephrotic syndrome (NS) is a common chronic kidney disease that is often accompanied by a state of immunodeficiency. Immunosuppression increases the risk of infections, with Pneumocystis jirovecii and Nocardia brasiliensis being two opportunistic pathogens that can cause severe infections in patients with compromised immune function. This study presents a case of a middle-aged male patient with NS concurrently infected with Pneumocystis jirovecii and Nocardia brasiliensis. It aims to synthesize the pertinent diagnostic approaches and treatment experiences. Notably, there have been no reported cases of NS occurring simultaneously with both Pneumocystis jirovecii pneumonia and Nocardia pneumonia. CASE PRESENTATION: A 58-year-old male farmer presented to the hospital with a one-week history of persistent fever, cough, and sputum production. His maximum body temperature was recorded at 39 °C, and he produced yellow viscous sputum. This patient had a one-year history of NS, managed with long-term oral corticosteroid and cyclophosphamide therapy. Admission chest computed tomography displayed interstitial changes in both lungs. After failing to detect any pathogens through routine etiological tests, we successfully identified Nocardia brasiliensis, Pneumocystis jirovecii, and Lodderomyces elongisporus using bronchoscopy-guided sputum samples through metagenomic next-generation sequencing (mNGS) technology. Subsequently, we initiated a combined treatment regimen for the patient using trimethoprim-sulfamethoxazole, meropenem, and moxifloxacin, which yielded remarkable therapeutic outcomes. CONCLUSION: The adoption and promotion of mNGS technologies have significantly resolved the difficulty in early pathogen detection, guiding clinicians from empirical to genomic diagnosis, achieving prevention before treatment, and thereby enhancing patient survival rates.
Assuntos
Síndrome Nefrótica , Nocardiose , Nocardia , Pneumocystis carinii , Pneumonia por Pneumocystis , Humanos , Masculino , Pessoa de Meia-Idade , Pneumocystis carinii/isolamento & purificação , Pneumocystis carinii/genética , Síndrome Nefrótica/complicações , Pneumonia por Pneumocystis/tratamento farmacológico , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/microbiologia , Pneumonia por Pneumocystis/complicações , Nocardia/isolamento & purificação , Nocardia/genética , Nocardiose/tratamento farmacológico , Nocardiose/microbiologia , Nocardiose/diagnóstico , Nocardiose/complicações , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/complicações , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/diagnósticoRESUMO
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.
Assuntos
Antibacterianos , Quimioterapia Combinada , Infecções por Klebsiella , Klebsiella pneumoniae , Polimixina B , Tigeciclina , Humanos , Polimixina B/administração & dosagem , Polimixina B/uso terapêutico , Polimixina B/efeitos adversos , Masculino , Estudos Retrospectivos , Tigeciclina/administração & dosagem , Tigeciclina/uso terapêutico , Tigeciclina/efeitos adversos , Feminino , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/mortalidade , Infecções por Klebsiella/epidemiologia , Infecções por Klebsiella/microbiologia , Idoso , Klebsiella pneumoniae/efeitos dos fármacos , Pessoa de Meia-Idade , Carbapenêmicos/uso terapêutico , Carbapenêmicos/efeitos adversos , Carbapenêmicos/administração & dosagem , Resultado do Tratamento , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/mortalidadeRESUMO
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.
Assuntos
COVID-19 , Pneumonia Bacteriana , SARS-CoV-2 , Humanos , Masculino , COVID-19/complicações , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/diagnóstico , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêuticoRESUMO
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.
Assuntos
Antibacterianos , Farmacorresistência Bacteriana Múltipla , Infecções por Pseudomonas , Pseudomonas aeruginosa , Humanos , Masculino , Feminino , Pseudomonas aeruginosa/efeitos dos fármacos , Estudos Retrospectivos , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Idoso , Pessoa de Meia-Idade , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/mortalidade , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Pneumonia Associada à Ventilação Mecânica/microbiologia , Pneumonia Associada à Ventilação Mecânica/mortalidade , Resultado do Tratamento , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/mortalidade , Duração da TerapiaRESUMO
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.
Assuntos
Antibacterianos , Gestão de Antimicrobianos , Humanos , Antibacterianos/uso terapêutico , Pneumonia/tratamento farmacológico , Sistemas de Registro de Ordens Médicas , Adulto , Pneumonia Bacteriana/tratamento farmacológicoRESUMO
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.
Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Carbapenêmicos , Estado Terminal , Microbiota , Humanos , Acinetobacter baumannii/isolamento & purificação , Acinetobacter baumannii/efeitos dos fármacos , Masculino , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Feminino , Pessoa de Meia-Idade , Infecções por Acinetobacter/microbiologia , Infecções por Acinetobacter/tratamento farmacológico , Microbiota/efeitos dos fármacos , Idoso , Unidades de Terapia Intensiva/estatística & dados numéricos , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/tratamento farmacológico , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Escarro/microbiologia , Respiração Artificial/efeitos adversosRESUMO
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.
Assuntos
Antibacterianos , Peptídeos Antimicrobianos , Klebsiella pneumoniae , Staphylococcus aureus Resistente à Meticilina , Testes de Sensibilidade Microbiana , Infecção dos Ferimentos , Animais , Camundongos , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/uso terapêutico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Peptídeos Antimicrobianos/farmacologia , Peptídeos Antimicrobianos/química , Peptídeos Antimicrobianos/uso terapêutico , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/microbiologia , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Feminino , Modelos Animais de Doenças , Humanos , Dermatopatias Bacterianas/tratamento farmacológico , Dermatopatias Bacterianas/microbiologiaRESUMO
Administration of antibiotics via inhalation is considered an effective strategy for pneumonia treatment; however, it encounters challenges related to the development of drug formulations with precise particle sizes and controlled release profiles. Herein, size-tailored and acid-degradable polyvinyl alcohol (PVA) microgels are utilized for nebulized inhalation delivery of piperacillin (PIP) antibiotics to effectively treat pneumonia. These microgels loaded with PIP (G@PIP) were prepared through the UV-crosslinking of thermo-triggered vinyl ether methacrylate-functionalized PVA (PVAVEMA) micro-aggregates in aqueous solution. The size of G@PIP microgels could be tailored by adjusting concentrations during the crosslinking process above phase-transition temperature at 15 °C. Additionally, under simulated inflammatory acidic conditions, the G@PIP microgels degraded and released PIP with relatively high inhibition efficiency against E. coli. Furthermore, in vivo therapeutic outcomes revealed that inhalational delivery of G@PIP microgel with a medium-size of 3.5 µm (G-3.5@PIP) exhibited superior lung deposition compared to other microgel sizes owing to its reduced exhalation and enhanced diffusion capacity within the pulmonary system. The high accumulation of G-3.5@PIP significantly reduced E. coli infection and associated inflammation while maintaining the biocompatibility of the microgels. Overall, these acid-degradable PVA microgels offer a versatile and efficacious inhalation therapy for pneumonia-associated infections.
Assuntos
Antibacterianos , Escherichia coli , Microgéis , Tamanho da Partícula , Pneumonia Bacteriana , Álcool de Polivinil , Álcool de Polivinil/química , Microgéis/química , Antibacterianos/química , Antibacterianos/farmacologia , Antibacterianos/administração & dosagem , Administração por Inalação , Pneumonia Bacteriana/tratamento farmacológico , Animais , Escherichia coli/efeitos dos fármacos , Camundongos , Testes de Sensibilidade Microbiana , HumanosRESUMO
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.
Assuntos
Antibacterianos , Infecções por Bactérias Gram-Negativas , Pneumonia Bacteriana , Shewanella , Humanos , Masculino , Shewanella/isolamento & purificação , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/diagnóstico , Pneumonia Bacteriana/complicações , Antibacterianos/uso terapêutico , Tibet , Ceftazidima/uso terapêutico , Ceftazidima/administração & dosagem , IdosoRESUMO
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.
Assuntos
Antibacterianos , Humanos , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Lactente , Recém-Nascido , Ensaios Clínicos Controlados Aleatórios como Assunto , Pneumonia/tratamento farmacológico , Resultado do Tratamento , Pneumonia Bacteriana/tratamento farmacológicoRESUMO
PURPOSE: The incidence of pneumonia caused by multidrug-resistant gram-negative bacteria (MDR GNB) is increasing, which imposes significant burden on public health. Inhalation combined with intravenous polymyxins has emerged as a viable treatment option. However, pharmacokinetic studies focusing on intravenous and inhaled polymyxin B (PMB) are limited. METHODS: This study included seven patients with MDR GNB-induced pneumonia who were treated with intravenous plus inhaled PMB from March 1 to November 30, 2022, in the intensive care unit of the First Affiliated Hospital of Zhejiang University School of Medicine. Clinical outcomes and therapeutic drug monitoring data of PMB in both plasma and epithelial lining fluid (ELF) were retrospectively reviewed. RESULTS: Median PMB concentrations in the ELF were 7.83 (0.72-66.5), 116.72 (17.37-571.26), 41.1 (3.69-133.78) and 33.82 (0.83-126.68) mg/L at 0, 2, 6 and 12 h, respectively, and were much higher than those detected in the serum. ELF concentrations of PMB at 0, 2, 6 and 12 h were higher than the minimum inhibitory concentrations of pathogens isolated from the patients. Steady-state concentrations of PMB in the plasma were >2 mg/L in most patients. Of the patients, 57.14% were cured and 71.43% showed a favourable microbiological response. The incidence of side effects with PMB was low. CONCLUSIONS: Inhaled plus intravenous PMB can achieve high ELF concentrations and favourable clinical outcomes without an increased adverse effect profile. This treatment approach appears promising for the treatment of patients with pneumonia caused by MDR-GNB.
Assuntos
Administração Intravenosa , Antibacterianos , Farmacorresistência Bacteriana Múltipla , Infecções por Bactérias Gram-Negativas , Pneumonia Bacteriana , Polimixina B , Humanos , Polimixina B/administração & dosagem , Polimixina B/farmacocinética , Polimixina B/uso terapêutico , Masculino , Feminino , Antibacterianos/farmacocinética , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Pessoa de Meia-Idade , Administração por Inalação , Estudos Retrospectivos , Idoso , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/microbiologia , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Resultado do Tratamento , Bactérias Gram-Negativas/efeitos dos fármacos , Adulto , Testes de Sensibilidade Microbiana , Unidades de Terapia IntensivaRESUMO
BACKGROUND: Available descriptive studies on equine pneumonia are outdated or focus on specific horse or bacterial populations. OBJECTIVES: To describe the clinical presentation and bacterial isolates of adult horses with bacterial pneumonia and identify factors associated with death. ANIMALS: One hundred sixteen horses >2 years old with bacterial pneumonia. METHODS: Retrospective case series. Data regarding history, physical examination, clinicopathologic features, treatment, bacterial culture and sensitivity, and outcome were collected and analyzed retrospectively. RESULTS: Historical risk factors were present for 60% of cases, whereas abnormal vital signs on intake were present for <50%. Most horses (58%) underwent at least 1 change of antimicrobial treatment, and 67% received the highest-priority critically important antimicrobials. Streptococcus zooepidemicus was the most isolated bacteria (44%), followed by Escherichia coli (19%), Klebsiella spp. (18%), other Streptococcus species (17%), and Bacillus spp. (13%). Fusobacterium spp. were the most common anaerobic isolates (11%). Antimicrobial susceptibility varied widely. Survival to discharge was 73%. Heart rate at presentation (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.008-1.17, P = .03) and higher creatinine (OR 14.1, 95% CI 1.56-127.6, P = .02) increased the risk of death. Higher lymphocyte count (OR 0.27, 95% CI 0.08-0.94, P = .04) reduced risk. CONCLUSIONS AND CLINICAL IMPORTANCE: Contrasting older literature, Fusobacterium spp. were the most common anaerobes. Streptococcus zooepidemicus remained the most common isolate and was predictably susceptible to penicillin. Antimicrobial susceptibility was otherwise variable and broad applicability is limited as this was a single-center study. Increased risk of death associated with tachycardia and abnormally high serum creatinine concentration is consistent with previous studies.
Assuntos
Antibacterianos , Doenças dos Cavalos , Pneumonia Bacteriana , Animais , Cavalos , Estudos Retrospectivos , Doenças dos Cavalos/microbiologia , Doenças dos Cavalos/mortalidade , Pneumonia Bacteriana/veterinária , Pneumonia Bacteriana/mortalidade , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/tratamento farmacológico , Masculino , Feminino , Fatores de Risco , Antibacterianos/uso terapêuticoAssuntos
Gestão de Antimicrobianos , Estado Terminal , Humanos , Gestão de Antimicrobianos/métodos , Antibacterianos/uso terapêutico , Pneumonia Bacteriana/diagnóstico , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia/diagnóstico , Pneumonia/tratamento farmacológico , Técnicas Bacteriológicas/métodosRESUMO
BACKGROUND: Legionella maceachernii pneumonia is a severe respiratory infection with low incidence but high mortality. However, the optimal treatment for this disease remains unclear. We report a case of successful treatment of Legionella maceachernii pneumonia, which is the first report of such a case in China. CASE PRESENTATION: An 87-year-old man with concomitant chronic obstructive pulmonary disease, liver cirrhosis, and history of left nephrectomy was diagnosed with Legionella maceachernii pneumonia using Dano-seq pathogen metagenomic testing. After two weeks of treatment with cefoperazone/sulbactam combined with quinolone antibiotics, the patient showed improvement and was discharged. The patient continued to take oral quinolone antibiotics for one week after discharge and recovered during outpatient follow-up. CONCLUSIONS: Dano-seq pathogen metagenomic testing can rapidly diagnose Legionella maceachernii pneumonia, and taking quinolone antibiotics is an effective treatment.
Assuntos
Antibacterianos , Legionella , Legionelose , Humanos , Masculino , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Idoso de 80 Anos ou mais , Legionella/isolamento & purificação , Legionelose/diagnóstico , Legionelose/tratamento farmacológico , Legionelose/microbiologia , Cefoperazona/uso terapêutico , Cefoperazona/administração & dosagem , Sulbactam/uso terapêutico , Sulbactam/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/complicações , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/diagnóstico , Pneumonia Bacteriana/tratamento farmacológico , Cirrose Hepática/complicaçõesRESUMO
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.
Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Metagenômica , Tropheryma , Doença de Whipple , Humanos , Tropheryma/genética , Tropheryma/isolamento & purificação , Doença de Whipple/diagnóstico , Doença de Whipple/tratamento farmacológico , Doença de Whipple/microbiologia , Masculino , Metagenômica/métodos , Pessoa de Meia-Idade , Idoso , Feminino , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/diagnóstico , Pneumonia Bacteriana/tratamento farmacológico , Antibacterianos/uso terapêuticoAssuntos
Burkholderia pseudomallei , Melioidose , Sepse , Humanos , Melioidose/tratamento farmacológico , Melioidose/diagnóstico , Sepse/microbiologia , Sepse/tratamento farmacológico , Burkholderia pseudomallei/isolamento & purificação , Masculino , Antibacterianos/uso terapêutico , Viagem , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/tratamento farmacológico , Pessoa de Meia-IdadeRESUMO
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.
Assuntos
Antibacterianos , Colistina , Pneumonia Bacteriana , Polimixina B , Humanos , Polimixina B/uso terapêutico , Polimixina B/administração & dosagem , Masculino , Colistina/uso terapêutico , Colistina/efeitos adversos , Colistina/administração & dosagem , Feminino , Antibacterianos/uso terapêutico , Pessoa de Meia-Idade , Idoso , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/microbiologia , Estudos Retrospectivos , Acinetobacter baumannii/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Resultado do Tratamento , Adulto , Bactérias Gram-Negativas/efeitos dos fármacos , Unidades de Terapia Intensiva , Pseudomonas aeruginosa/efeitos dos fármacos , Idoso de 80 Anos ou mais , Klebsiella pneumoniae/efeitos dos fármacosRESUMO
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.