The angiotensin-(1-7)/MasR axis improves pneumonia caused by Pseudomonas aeruginosa: Extending the therapeutic window for antibiotic therapy.

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.

Microbial variations in sputum cultures among hospitalized patients with community-acquired pneumonia: differences in sputum microbiota between asthma and COPD patients.

OBJECTIVE: To assess differences in the sputum microbiota of community-acquired pneumonia (CAP) patients with either COPD or asthma, specifically focusing on a patient population in Turkey. METHODS: This retrospective study included hospitalized patients > 18 years of age with a diagnosis of pneumonia between January of 2021 and January of 2023. Participants were recruited from two hospitals, and three patient groups were considered: CAP patients with asthma, CAP patients with COPD, and CAP patients without COPD or asthma. RESULTS: A total of 246 patients with CAP were included in the study, 184 (74.8%) and 62 (25.2%) being males and females, with a mean age of 66 ± 14 years. Among the participants, 52.9% had COPD, 14.2% had asthma, and 32.9% had CAP but no COPD or asthma. Upon analysis of sputum cultures, positive sputum culture growth was observed in 52.9% of patients. The most commonly isolated microorganisms were Pseudomonas aeruginosa (n = 40), Acinetobacter baumannii (n = 20), Klebsiella pneumoniae (n = 16), and Moraxella catarrhalis (n = 8). CAP patients with COPD were more likely to have a positive sputum culture (p = 0.038), a history of antibiotic use within the past three months (p = 0.03), utilization of long-term home oxygen therapy (p < 0.001), and use of noninvasive ventilation (p = 0.001) when compared with the other patient groups. Additionally, CAP patients with COPD had a higher CURB-65 score when compared with CAP patients with asthma (p = 0.004). CONCLUSIONS: This study demonstrates that CAP patients with COPD tend to have more severe presentations, while CAP patients with asthma show varied microbial profiles, underscoring the need for patient-specific management strategies in CAP.

Investigation of etiology of community-acquired pneumonia in hospitalized patients in a tertiary hospital of São Paulo City, Brazil.

BACKGROUND: Community-Acquired Pneumonia (CAP) is the primary cause of hospitalization in the United States and the third leading cause of death in Brazil. The gold standard for diagnosing the etiology of CAP includes blood culture, Gram-stained sputum, and sputum culture. However, these methods have low sensitivity. No studies investigating the etiology of CAP have been conducted in Brazil in the last 20-years, and the empirical choice of antimicrobials is mainly based on the IDSA guidelines. This is the first national study with this aim, and as a result, there's potential for the Brazilian consensus to be impacted and possibly modify its guidelines rather than adhering strictly to the IDSA's recommendations. METHODS: The aim of this study is to identify the main microorganisms implicated in CAP by employing a multiplex Polymerase Chain Reaction (mPCR) at the foremost public hospital in Brazil. All patients who were admitted to the emergency department and diagnosed with severe CAP underwent an mPCR panel using nasopharyngeal and oropharyngeal swabs, with the aim of detecting 13 bacterial and 21 viral pathogens. RESULTS: A total of 169 patients were enrolled in the study. The mPCR panel identified an etiological agent in 61.5% of patients, with viruses being the most common (42.01%), led by Rhinovirus, followed by Influenza and Coronavirus (non-SARS-CoV-2). Bacterial agents were identified in 34.91% of patients, with S. pneumoniae being the most common, followed by H. influenzae, M. catarrhalis, and S. aureus. Additionally, we found that the prescription for 92.3% of patients could be modified, with most changes involving de-escalation of antibiotics and antiviral therapy. CONCLUSION: Our study revealed different etiological causes of CAP than those suggested by the Brazilian guidelines. Using molecular diagnostic tests, we were able to optimize treatment by using fewer antibiotics.

The Therapeutic Treatment with the GAG-Binding Chemokine Fragment CXCL9(74-103) Attenuates Neutrophilic Inflammation and Lung Dysfunction during Klebsiella pneumoniae Infection in Mice.

Klebsiella pneumoniae is an important pathogen associated with hospital-acquired pneumonia (HAP). Bacterial pneumonia is characterized by a harmful inflammatory response with a massive influx of neutrophils, production of cytokines and chemokines, and consequent tissue damage and dysfunction. Targeted therapies to block neutrophil migration to avoid tissue damage while keeping the antimicrobial properties of tissue remains a challenge in the field. Here we tested the effect of the anti-inflammatory properties of the chemokine fragment CXCL9(74-103) in pneumonia induced by Klebsiella pneumoniae in mice. Mice were infected by intratracheal injection of Klebsiella pneumoniae and 6 h after infection were treated systemically with CXCL9(74-103). The recruitment of leukocytes, levels of cytokines and chemokines, colony-forming units (CFU), and lung function were evaluated. The treatment with CXCL9(74-103) decreased neutrophil migration to the airways and the production of the cytokine interleukin-1ß (IL-1ß) without affecting bacterial control. In addition, the therapeutic treatment improved lung function in infected mice. Our results indicated that the treatment with CXCL9(74-103) reduced inflammation and improved lung function in Klebsiella pneumoniae-induced pneumonia.

Diversity in the composition of the accessory genome of Mexican Pseudomonas aeruginosa strains.

BACKGROUND: Pseudomonas aeruginosa is an important opportunistic pathogen especially in nosocomial infections due to its easy adaptation to different environments; this characteristic is due to the great genetic diversity that presents its genome. In addition, it is considered a pathogen of critical priority due to the high antimicrobial resistance. OBJECTIVES: The aim of this study was to characterize the mobile genetic elements present in the chromosome of six Mexican P. aeruginosa strains isolated from adults with pneumonia and children with bacteremia. METHODS: The genomic DNA of six P. aeruginosa strains were isolated and sequenced using PacBio RS-II platform. They were annotated using Prokaryotic Genome Annotation Pipeline and manually curated and analyzed for the presence of mobile genetic elements, antibiotic resistances genes, efflux pumps and virulence factors using several bioinformatics programs and databases. RESULTS: The global analysis of the strains chromosomes showed a novel chromosomal rearrangement in two strains, possibly mediated by subsequent recombination and inversion events. They have a high content of mobile genetic elements: 21 genomic islands, four new islets, four different integrative conjugative elements, 28 different prophages, one CRISPR-Cas arrangements, and one class 1 integron. The acquisition of antimicrobials resistance genes into these elements are in concordance with their phenotype of multi-drug resistance. CONCLUSION: The accessory genome increased the ability of the strains to adapt or survive to the hospital environment, promote genomic plasticity and chromosomal rearrangements, which may affect the expression or functionality of the gene and might influence the clinical outcome, having an impact on the treatment.

Aspectos epidemiológicos, clínicos y microbiológicos en pacientes menores de 5 años con neumonía bacteriana / Epidemiological, clinical and microbiologic aspects in patients under 5 years with bacterial pneumonia

Introducción: Las infecciones respiratorias agudas abarcan entre 20 y 40 % del total de todas las hospitalizaciones y 20 - 34 % de las muertes en menores de 5 años de edad, fundamentalmente a expensas de neumonía. Objetivo: Describir aspectos epidemiológicos, clínicos y microbiológicos en pacientes menores de 5 años con neumonía bacteriana. Métodos: Se realizó un estudio descriptivo y transversal de 39 pacientes con neumonía y aislamientos bacterianos en hemocultivos, líquido pleural y/o exudados nasofaringeos, ingresados en el Hospital Infantil Docente Sur Antonio María Béguez Cesar de Santiago de Cuba, desde enero de 2018 hasta diciembre de 2019. Se analizaron variables de interés, tales como edad, sexo, factores de riesgo, sintomatología y cultivos microbiológicos. Se utilizaron la frecuencia absoluta y el porcentaje como medidas de resumen. Resultados: Prevalecieron los pacientes entre 1 - 4 años de edad, el sexo femenino y los hemocultivos con estafilococos coagulasa negativo, así como neumococos, estos últimos también aislados en exudados nasofaríngeos. Los factores de riesgo más frecuentes fueron infección respiratoria aguda previa, uso anticipado de antibióticos, asistencia a círculo infantil, supresión precoz de lactancia materna, fiebre, tos, tiraje y alteraciones del murmullo vesicular. Predominaron la insuficiencia respiratoria aguda y el derrame pleural como complicaciones. Se notificó más gravedad en los lactantes y ocurrieron 2 decesos, para una letalidad de 1,47 %. Conclusiones: La conjunción de factores de riesgo detectados, la baja positividad de los cultivos, la identificación de bacterias prevalentes en hemocultivos y el descenso de la letalidad resultaron de interés en el estudio.

Introduction: Acute respiratory infections take in between 20 and 40 % of all the hospitalizations and 20 - 34% of deaths in children under 5 years, fundamentally at the expense of pneumonia. Objective: To describe epidemiologic, clinical and microbiologic aspects in patients under 5 years with bacterial pneumonia. Methods: A descriptive and cross-sectional study of 39 patients with pneumonia and bacterial isolations in hemocultures, pleural fluid and/or nasopharyngeal swabs was carried out. They were admitted to Antonio María Béguez Cesar Southern Teaching Children Hospital in Santiago de Cuba, from January, 2018 to December, 2019. Variables of interest were analyzed, such as age, sex, risk factors, symptomatology and microbiologic cultures. The absolute frequency and the percentage as summary measures were used. Results: There was a prevalence of patients among 1 - 4 years, female sex and the hemocultures with negative coagulase staphylococcu, as well as pneumococus, these last ones also isolated in nasopharingeal swabs. The most frequent risk factors were previous acute respiratory infection, premature use of antibiotics, attendance to day care center, early suppression of breastfeeding, fever, cough, tirage and changes of the vesicular breath sound. The acute respiratory failure and pleural effusion as complications prevailed. More seriousness was notified in infants and there were 2 deaths, for a letality of 1.47 %. Conclusions: The combination of detected risk factors, low positivity of the cultures, identification of bacterias prevalents in hemocultures and the decrease of letality was of interest in the study.

Pulmonary and thoracic infection by Fusobacterium nucleatum. / Infección pulmonar y torácica por Fusobacterium nucleatum.

INTRODUCTION: Fusobacterium nucleatum is an anaerobic bacillus that is part of the oral microbiota and dental pla que. This can cause local and potentially remote infections, which are exceptional in pediatrics. Ob jective: To present the case of a patient with lung injury with chest wall invasion by Fusobacterium nucleatum. CLINICAL CASE: An 11-year-old female immunocompetent patient who consulted due to a two-week history of cough, night sweats, without fever or weight loss, and increased volume at the left spleen thoracic level. There was no history of chest wall trauma or travel outside the country. Two weeks before the onset of symptoms, she was treated for dental caries. Imaging studies and CT scan showed left spleen pneumonia, which invades the pleura and the chest wall. A minimal thoracotomy was performed, releasing a thick, foul-smelling liquid. The studies for common germs and tubercu losis were negative. Hematology ruled out tumor lesions. The anaerobic study reported the develo pment of Fusobacterium nucleatum. The patient was treated with penicillin followed by amoxicillin presenting good clinical and radiological responses. The dental procedure was suspected as the cause of infection. CONCLUSIONS: Fusobacterium nucleatum can occasionally cause remote or extra-oral in fections in immunocompetent patients, such as pneumonia with chest wall invasion, therefore it is necessary to bear it in mind.

A short synthetic peptide, based on LyeTx I from Lycosa erythrognatha venom, shows potential to treat pneumonia caused by carbapenem-resistant Acinetobacter baumannii without detectable resistance.

The emergence of antibiotic-resistant bacteria, especially carbapenem-resistant Acinetobacter baumannii (CRAB), together with relative stagnation in the development of effective antibiotics, has led to enormous health and economic problems. In this study, we aimed to describe the antibacterial spectrum of LyeTx I mnΔK, a short synthetic peptide based on LyeTx I from Lycosa erythrognatha venom, against CRAB. LyeTx I mnΔK showed considerable antibacterial activity against extensively resistant A. baumannii, with minimum inhibitory and bactericidal concentrations ranging from 1 to 16 µM and 2 to 32 µM, respectively. This peptide significantly increased the release of 260 nm-absorbing intracellular material from CRAB, suggesting bacteriolysis. LyeTx I mnΔK was shown to act synergistically with meropenem and colistin against CRAB. The cytotoxic concentration of LyeTx I mnΔK against Vero cells (CC50 = 55.31 ± 5.00 µM) and its hemolytic activity (HC50 = 77.07 ± 4.00 µM) were considerably low; however, its antibacterial activity was significantly reduced in the presence of human and animal serum and trypsin. Nevertheless, the inhalation of this peptide was effective in reducing pulmonary bacterial load in a mouse model of CRAB infection. Altogether, these results demonstrate that the peptide LyeTx I mnΔK is a potential prototype for the development of new effective and safe antibacterial agents against CRAB.

Elastase Activity From Pseudomonas aeruginosa Respiratory Isolates and ICU Mortality.

BACKGROUND: Pseudomonas aeruginosa (PA) is a common cause of respiratory infection and morbidity. Pseudomonas elastase is an important virulence factor regulated by the lasR gene. Whether PA elastase activity is associated with worse clinical outcomes in ICU patients is unknown. RESEARCH QUESTION: Is there an association between PA elastase activity and worse host outcomes in a cohort of ICU patients? METHODS: PA respiratory isolates from 238 unique ICU patients from two tertiary-care centers within the University of Pittsburgh Medical Center health system were prospectively collected and screened for total protease and elastase activity, biofilm production, antimicrobial resistance, and polymicrobial status. The association between pathogen characteristics and 30-day and 90-day mortality was calculated using logistic regression. For subgroup analysis, two patterns of early (≤72 h) and late sample (>72 h) collection from the index ICU admission were distinguished using a finite mixture model. Lung inflammation and injury was evaluated in a mouse model using a PA high elastase vs low elastase producer. RESULTS: PA elastase activity was common in ICU respiratory isolates representing 75% of samples and was associated with increased 30-day mortality (adjusted OR [95% CI]: 1.39 [1.05-1.83]). Subgroup analysis demonstrated that elastase activity was a risk factor for 30- and 90-day mortality in the early sample group, whereas antimicrobial resistance was a risk factor for 90-day mortality in the late sample group. Whole genome sequencing of high and low elastase producers showed that predicted loss-of-function lasR genotypes were less common among high elastase producers. Mice infected with a high elastase producer showed increased lung bacterial burden and inflammatory profile compared with mice infected with a low elastase producer. INTERPRETATION: Elastase activity is associated with 30-day ICU mortality. A high elastase producing clinical isolate confers increased lung tissue inflammation compared with a low elastase producer in vivo.

Pneumocystis jiroveci pneumonia, Nocardia brasiliensis, and Mycobacterium tuberculosis co-infection in a myasthenia gravis patient: A case report.

RATIONALE: Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junctions that leads to fluctuating weakness and disabling fatigability. Due to difficulty in breathing caused by weakness of the respiratory muscles, patients with MG are more susceptible to pneumonia and other respiratory infections. As many patients with MG are given immunosuppressive therapy, this makes them more prone to infections. However, coinfection with 3 pathogens is very rare. PATIENT CONCERNS: Here, we report the case of a 41-year-old gentleman with MG who was receiving long-term steroid therapy. He presented with a cough with pale brown expectoration that occurred without obvious inducement, severe pain in the scapula, as well as swelling and weakness of both legs. Despite undergoing treatment, but his symptoms did not improve, prompting two additional hospital admissions over a period of several months. DIAGNOSIS: Bronchoscopy and bronchoalveolar lavage (BAL) were performed, revealing the presence of Pneumocystis jirovecii , Nocardia brasiliensis, and Mycobacterium tuberculosis (MTB). N brasiliensis was identified by positive modified acid-fast Kinyoun staining as well as a positive colony culture identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry from the BAL sample. MTB was confirmed using GeneXpert, and due to the limitations of the culture conditions, methenamine silver stain was used to confirm Pneumocystis jirovecii. Next-generation sequencing (NGS) assay of the BAL samples also confirmed these pathogens. INTERVENTIONS: The patient was transferred to a designated tuberculosis hospital and received anti-infective and anti-TB treatment. OUTCOMES: During treatment at the designated hospital, the patient developed gastrointestinal bleeding and impaired liver function. One month later, he developed multiple organ failure, consolidation of the left lower lung, and pan-drug resistant bacteremia. He refused further treatment and was discharged. CONCLUSION: In conclusion, physicians should be aware of the predisposition of MG patients to co-infections, especially patients with metabolic disorders, to avoid inadequate treatment and poor patient outcomes. Due to the limitations of culture conditions, NGS should be considered as a new technique for identifying pathogens.

COMPLICATED PNEUMONIA WITH EMPYEMA CAUSED BY STREPTOCOCCUS ANGINOSUS IN A CHILD.

OBJECTIVE: To highlight the pathogenicity of Streptococcus anginosus, which is rare in pediatric patients, but can cause severe infections that are known to have a better outcome when treated early with interventional procedures and prolonged antibiotic therapy. CASE: description: The patient is a 6-year-old boy with global developmental delay, examined in the emergency room due to fever and respiratory distress. The physical examination and diagnostic workout revealed complicated pneumonia with empyema of the left hemithorax; he started antibiotic therapy and underwent thoracic drainage. Pleural fluid cultures grew Streptococcus anginosus. On day 11, the child had a clinical deterioration with recurrence of fever, hypoxia, and respiratory distress. At this point, considering the causative agent, he was submitted to video-assisted thoracoscopic decortication, with good progress thereafter. COMMENTS: Streptococcus anginosus is a commensal bacterium of the human oral cavity capable of causing severe systemic infections. Although reports of complicated thoracic infections with this agent are rare in the pediatric population, they have been increasing in adults. Streptococcus anginosus has a high capacity to form abscess and empyema, requiring different therapeutic approaches when compared to complicated pneumonia caused by other agents.

PATHOLOGIC FINDINGS IN 36 SLOTHS FROM BRAZIL.

Sloths are xenarthrans from Central and South America with a highly adapted morphophysiology. Five of the six known species of sloths are found in Brazil, among which Bradypus torquatus (maned three-toed sloth) is considered a vulnerable species by International Union for Conservation of Nature. Nevertheless, knowledge on health and disease of sloths is very scarce, thus this study aimed to describe macroscopic and microscopic findings in 36 Brazilian sloths. The most common findings included iron storage disorder, probable bacterial pneumonia, gastric and intestinal nematode parasitism, and a presumptive diagnosis of systemic mastocytosis.

Antibacterial, anti-biofilm and in vivo activities of the antimicrobial peptides P5 and P6.2.

Cationic antimicrobial peptides (AMPs) are short linear amino acid sequences, which display antimicrobial activity against a wide range of bacterial species. They are promising novel antimicrobials since they have shown bactericidal effects against multiresistant bacteria. Their amphiphilic structure with hydrophobic and cationic regions drives their interaction with anionic bacterial cytoplasmic membranes, which leads to their disruption. In this work two synthetic designed AMPs, P5 and P6.2, which have been previously analyzed in their ability to interact with bacterial or eukaryotic membranes, were evaluated in their anti-biofilm and in vivo antibacterial activity. In a first step, a time-kill kinetic assay against P. aeruginosa and S. aureus and a curve for hemolytic activity were performed in order to determine the killing rate and the possible undesirable toxic effect, respectively, for both peptides. The biofilm inhibitory activity was quantified at sub MIC concentrations of the peptides and the results showed that P5 displayed antibiofilm activity on both strains while P6.2 only on S. aureus. Scanning electron microscopy (SEM) of bacteria treated with peptides at their MIC revealed protruding blisters on Gam-negative P. aeruginosa strain, but almost no visible surface alteration on Gram-positive S. aureus. These micrographs highlighted different manifestations of the membrane-disrupting activity that these kinds of peptides possess. Finally, both peptides were analyzed in vivo, in the lungs of neutropenic mice previously instilled with P. aeruginosa. Mice lungs were surgically extracted and bacteria and pro-inflammatory cytokines (IL-ß, IL-6 and TNF-α) were quantified by colony forming units and ELISA, respectively. Results showed that instillation of the peptides produced a significant decrease in the number of living bacteria in the lungs, concomitant with a decrease in pro-inflammatory cytokines. Overall, the results presented here suggest that these two new peptides could be good candidates for future drug development for anti-biofilm and anti-infective therapy.

Complicated pneumonia with empyema caused by streptococcus anginosus in a child / Complicated pneumonia with empyema caused by streptococcus anginosus in a child

ABSTRACT Objective: To highlight the pathogenicity of Streptococcus anginosus, which is rare in pediatric patients, but can cause severe infections that are known to have a better outcome when treated early with interventional procedures and prolonged antibiotic therapy. Case description: The patient is a 6-year-old boy with global developmental delay, examined in the emergency room due to fever and respiratory distress. The physical examination and diagnostic workout revealed complicated pneumonia with empyema of the left hemithorax; he started antibiotic therapy and underwent thoracic drainage. Pleural fluid cultures grew Streptococcus anginosus. On day 11, the child had a clinical deterioration with recurrence of fever, hypoxia, and respiratory distress. At this point, considering the causative agent, he was submitted to video-assisted thoracoscopic decortication, with good progress thereafter. Comments: Streptococcus anginosus is a commensal bacterium of the human oral cavity capable of causing severe systemic infections. Although reports of complicated thoracic infections with this agent are rare in the pediatric population, they have been increasing in adults. Streptococcus anginosus has a high capacity to form abscess and empyema, requiring different therapeutic approaches when compared to complicated pneumonia caused by other agents.

RESUMO Objetivo: Alertar para a patogenicidade do Streptococcus anginosus que, apesar de raro em pediatria, pode causar infeções graves que necessitam de tratamento invasivo e antibioterapia de longo curso para obter um melhor prognóstico. Descrição do caso: Criança de seis anos, com atraso do desenvolvimento psicomotor, avaliado no serviço de urgência por febre e dificuldade respiratória. O exame físico, juntamente com os exames complementares, revelou uma pneumonia complicada com empiema no hemitórax esquerdo, tendo iniciado antibioterapia e sido submetido à drenagem do líquido pleural. Foi identificado Streptococcus anginosus nesse líquido. No 11º dia de doença, a criança agravou o seu estado clínico, com recidiva da febre, hipoxemia e dificuldade respiratória. Considerando-se o microrganismo identificado, o paciente foi submetido à decorticação pulmonar por videotoracoscopia, com boa evolução clínica posterior. Comentários: Streptococcus anginosus é uma bactéria comensal da cavidade oral humana, que pode causar infecções sistêmicas graves. Apesar de serem raros os casos descritos em pediatria, têm sido cada vez mais descritas infecções torácicas complicadas em adultos. Esse microrganismo também tem a capacidade de formar abcessos e empiemas, que precisam de intervenções terapêuticas diferentes, quando comparados a pneumonias complicadas causadas por outros agentes.

Infection in cirrhosis: A prospective study.

INTRODUCTION AND OBJECTIVES: Multidrug-resistant (MDR) infections in cirrhosis are associated with poor outcomes. We attempted a prospective study on infections in patients with cirrhosis evaluating microbiology of these infections and how outcomes depended on factors like bacterial resistance, appropriate antibiotics, stage of liver disease and whether outcomes were significantly different from patients who did not have infections. MATERIALS AND METHODS: This was a prospective evaluation involving one hundred and fifty nine patients with cirrhosis who were admitted at Peerless Hospitex Hospital and Research Center, Kolkata, West Bengal, India, during a 24 month period. One hundred and nineteen of these patients either had an infection at the time of admission or developed infection during hospitalization. Forty patients did not have an infection at admission and did not acquire infection while admitted. Data was collected about demographics, etiology of cirrhosis, liver and renal function and microbiology. RESULTS: Infections were community acquired in 27.7% of patients, healthcare associated in 52.9% and nosocomial in 19.3%. Gram negative bacilli (Escherichia coli 47.4% Klebsiella pneumoniae 23%) were common. 84.9% of enterobacteriaceae produced ESBL, AmpC or Carbapenemases. Spontaneous bacteria peritonitis (SBP) and urinary tract infection (UTI) were the most common sites of infection. In hospital mortality was 21.9%. Non-survivors had higher MELD (26 vs 19, p<0.001) and CTP scores (11.7 vs 10.3, p<0.001). The control group had lower MELD (16.65 vs. 20.8, p<0.001) and CTP scores (9.25 vs 10.59, p<0.001). CONCLUSIONS: MDR infections are common in patients with cirrhosis and have serious implications for treatment and outcomes.

Delftia acidovorans pneumonia with lung cavities formation / Neumonia con formación de cavidades pulmonares causada por Delftia acidovorans

Abstract Case Description: A 52-year-old female patient was admitted to our clinic with complaints of cough, sputum, fever and fatigue. The patient has been receiving immunosuppressive therapy for thrombocytopenic purpura for 5 years. Clinical Finding: Inspiratory crackles were heard on both hemithorax. Oxygen saturation measured with the pulse oximeter was 97%. Chest X-ray showed diffuse reticular opacities that were more prominent in the upper zones of both lungs. WBC counts were 17,600 mm3 and Platelet counts were 29,000 mm3. Thorax CT showed that there were many thin-walled cavities and millimetric nodules accompanied by ground-glass infiltrates in the upper and middle lobes. Gram staining of bronchial fluid, taken by bronchoscopy, revealed Gram-negative bacilli and intense polymorphonuclear leukocytes. The bacteria were defined as Delftia acidovorans by BD Phoenix automated system. Treatment and outcomes: The patient was hospitalized with suspicion of opportunistic pulmonary infections and cavitary lung disease. After the empirical treatment of intravenous piperacillin-tazobactam and oral clarithromycin, her clinical and radiological findings significantly regressed, and she was discharged with outpatient follow-up. Clinical Relevance: This is the first example of cavitary pneumonia due to Delftia acidovorans in an immunocompromised patient. We would like to emphasize that Delftia pneumonia should be considered in the differential diagnosis of pulmonary cavitary involvement in such patients.

Resumen Descripción del caso: Una mujer de 52 años llegó a la clínica con tos, esputo, fiebre y fatiga. El paciente estuvo recibiendo terapia inmunosupresora durante 5 años para el tratamiento de la púrpura trombocitopénica. Hallazgo clínico: se escucharon crepitaciones inspiratorias en ambos hemitórax. La saturación de oxígeno fue del 97%. La radiografía de tórax mostró opacidades reticulares difusas que eran más prominentes en las zonas superiores de ambos pulmones. Los recuentos de leucocitos fueron de 17,600 mm3 y los recuentos de plaquetas fueron de 29,000 mm3. La TC de tórax mostró muchas cavidades de pared delgada y nódulos milimétricos acompañados de infiltrados vitrales en los lóbulos superior y medio. La tinción de Gram del líquido bronquial reveló bacilos gramnegativos y leucocitos polimorfonucleares. Las bacterias fueron identificadas como Delftia acidovorans. Tratamiento y resultados: La paciente fue hospitalizado con una sospecha de infección oportunista pulmonar y enfermedad pulmonar cavitaria. Después del tratamiento empírico de piperacilina-tazobactam intravenosa y claritromicina oral, los síntomas y signos retrocedieron significativamente, y fue dada de alta con seguimiento ambulatorio. Relevancia clínica: este es el primer registro de neumonía cavitaria causado por Delftia acidovorans en una paciente inmunocomprometida. Enfatizamos que la neumonía por Delftia debe considerarse en el diagnóstico diferencial de la afectación de la cavidad pulmonar en tales pacientes.

Ceftazidime-Avibactam as Salvage Therapy for Infections Caused by Enterobacteriales Coresistant to Carbapenems and Polymyxins.

In this article, we report a case series of patients with infections caused by Enterobacteriales coresistant to carbapenems and polymyxins who were treated with ceftazidime/avibactam (CAZ-AVI) salvage therapy on a compassionate-use protocol. We enrolled 29 adult patients in 3 centers that had an infection due to a resistant microorganism and for whom the treatments available were considered ineffective, treated them with CAZ-AVI, and assessed clinical and microbiological cure at the end of treatment and all-cause mortality at 14 days and 30 days. The antimicrobial susceptibility profile was determined using broth microdilution, and total genomic DNA was sequenced. Twelve (41.4%) patients had bacteremia, and 48.3% (14/29) of the infections were treated with combination therapy. All strains were producers of KPC-2 and were susceptible to CAZ-AVI (MIC90, 1 µg/ml). Clinical success was high (24/29 [82.7%; 95% confidence interval, 64.2 to 94.2%]), even for the bacteremic cases (75%). The 14-day and 30-day mortality rates were 9/29 (31%) and 15/29 (51.7%), respectively. The 14-day mortality rate for pneumonia was the same as that for bloodstream infections (33.3%) and although not significant, we found that patients with renal impairment that received adjusted doses of CAZ-AVI had high mortality (4/9 [44%]; P = 0.22). We concluded that CAZ-AVI is an option for the treatment of severe infections due to difficult-to-treat drug-resistant Enterobacteriales.

Wheezing independently predicts viral infection in children with community-acquired pneumonia.

AIM: To assess whether there was a difference in the frequency of symptoms and signs among children with community-acquired pneumonia (CAP) with viral or bacterial infection. METHODS: A prospective cross-sectional study was conducted in Salvador, Brazil. Children less than 5-years-old hospitalized with CAP were recruited. Viral or only bacterial infection was diagnosed by an investigation of 11 viruses and 8 bacteria. Bacterial infection was diagnosed by blood culture, detection of pneumococcal DNA in acute buffy coat, and serological tests. Viral infection was diagnosed by detection of respiratory virus in nasopharyngeal aspirate and serological tests. Viral infection comprised only viral or mixed viral-bacterial infection subgroups. RESULTS: One hundred and eighty-eight patients had a probable etiology established as only viral (51.6%), mixed viral-bacterial (30.9%), and only bacterial infection (17.5%). Asthma was registered for 21.4%. Report of wheezing (47.4% vs 21.2%; P = 0.006), rhonchi (38.0% vs 15.2%; P = 0.01), and wheezing detected on physical examination (51.0% vs 9.1%; P < 0.001) were the differences found. Among children with asthma, detected wheezing was the only different finding when children with viral infection were compared with those with only bacterial infection (75.0% vs 0%; P = 0.008). By multivariable analysis, viral infection (AdjOR [95% CI]: 9.6; 95%CI: 2.7-34.0), asthma (AdjOR [95% CI]: 4.6; 95%CI: 1.9-11.0), and age (AdjOR [95% CI]: 0.95; 95%CI: 0.92-0.97) were independently associated with wheezing on physical examination. The positive predictive value of detected wheezing for viral infection was 96.3% (95% CI: 90.4-99.1%). CONCLUSION: Wheezing detected on physical examination is an independent predictor of viral infection.