RESUMO
BACKGROUND Endoscopic inguinal hernia repair has become the preferred technique currently. The use of mesh to facilitate a tension-free reinforcement has become the standard of care during endoscopic totally extraperitoneal (TEP), laparoscopic transabdominal pre-peritoneal, and open inguinal hernia repair. Although uncommon, late-developing mesh infections, defined as those occurring in the surgical site months or years after the procedure, can lead to severe complications. To achieve the best possible outcome for the patient, prompt imaging and a multidisciplinary approach to management, including complete surgical removal of the contaminated mesh and proper antibiotic therapy, are crucial. CASE REPORT A 39-year-old woman presented with a 1-month history of intermittent fever, progressive lower abdominal pain and fullness, and purulent discharge from the abdominal wall. Her medical history was significant for an endoscopic right TEP inguinal hernia repair performed 3 years earlier, which involved the use of an anatomic mesh and titanium screws. Physical examination and ultrasound findings revealed a large preperitoneal abscess with cutaneous fistulization, secondary to a deep-seated mesh infection. Pseudomonas aeruginosa was identified as the causative pathogen. She underwent a 2-step surgical procedure, including an initial fistulectomy followed by endoscopic abscess drainage and surgical excision of the infected mesh, combined with antimicrobial therapy, resulting in an excellent clinical response and complete resolution. This strategy also allowed for an effective assessment of the abdominal wall integrity. CONCLUSIONS This case underscores the importance of considering late-developing mesh infections in patients presenting with abdominal symptoms who have previously undergone TEP hernia repair, even years after the initial surgery.
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Fístula Cutânea , Hérnia Inguinal , Telas Cirúrgicas , Humanos , Feminino , Hérnia Inguinal/cirurgia , Telas Cirúrgicas/efeitos adversos , Adulto , Fístula Cutânea/etiologia , Fístula Cutânea/microbiologia , Herniorrafia/efeitos adversos , Abscesso/microbiologia , Abscesso/etiologia , Infecções por Pseudomonas/etiologia , Infecção da Ferida Cirúrgica/microbiologia , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/terapia , Abscesso Abdominal/etiologia , Abscesso Abdominal/microbiologiaRESUMO
In April 2021, the South Eastern Sydney Local Health District Public Health Unit (Sydney, New South Wales, Australia) was notified of 3 patients with Pseudomonas aeruginosa infections secondary to skin piercings performed at the same salon. Active case finding through laboratories, clinician alerts, and monitoring hospital visits for piercing-related infections identified additional cases across New South Wales, and consumers were alerted. We identified 13 confirmed and 40 probable case-patients and linked clinical isolates by genomic sequencing. Ten confirmed case-patients had used the same brand and batch of aftercare solution. We isolated P. aeruginosa from opened and unopened bottles of this solution batch that matched the outbreak strain identified by genomic sequencing. Piercing-related infections returned to baseline levels after this solution batch was recalled. Early outbreak detection and source attribution via genomic sequencing are crucial for controlling outbreaks linked to contaminated products. Manufacturing standards for nonsterile cosmetic products and guidance for piercing aftercare warrant review.
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Infecções por Pseudomonas , Humanos , Infecções por Pseudomonas/epidemiologia , Infecções por Pseudomonas/etiologia , Assistência ao Convalescente , Austrália/epidemiologia , New South Wales/epidemiologia , Surtos de Doenças , Pseudomonas aeruginosaRESUMO
Background and Objectives: This study was conducted to investigate whether Pseudomonas aeruginosa (PA) infections of arteriovenous grafts (AVGs) recur more frequently than other bacterial infections following treatment with revision. Materials and Methods: Operative procedures, including total excision, subtotal excision, and revision, were performed on 60 patients to treat 65 AVG infections. Final outcomes were classified as no infection recurrence, infection recurrence, and death without prior recurrence. In the competing risk setting, the cumulative incidence was estimated using the cumulative incidence function and Gray's test, and the associations between outcomes and different variables were estimated using a subdistribution hazard (SDH) model. Results: Comparing AVG infections with and without recurrence, PA infection was not associated with a higher risk of infection recurrence (p = 0.13); however, the first operative procedure type was associated with infection recurrence (p = 0.04). AVGs with PA infection were associated with a higher total number of surgical interventions (p < 0.05) than AVGs without PA infection. Regarding the cumulative incidences of outcomes, for AVGs treated with subtotal excision or revision, the cumulative incidence of recurrent infection was 3.3-fold higher for those with PA infection than without one year after the first surgery. However, when AVGs were treated with revision alone, the cumulative incidence was 4.1-fold. After excluding AVGs treated with total excision, the SDH model was applied, obtaining a hazard ratio for infection recurrence of 16.05 (p = 0.02) for AVGs with PA infection compared with AVGs without PA infection. No other variables were significantly associated with infection recurrence. Conclusions: For subtotal resection and revision, AVGs infected with PA had a higher recurrence rate than those infected with other species. However, revision surgery may aggravate the recurrence rate.
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Derivação Arteriovenosa Cirúrgica , Implante de Prótese Vascular , Infecções por Pseudomonas , Humanos , Implante de Prótese Vascular/efeitos adversos , Grau de Desobstrução Vascular , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Infecções por Pseudomonas/epidemiologia , Infecções por Pseudomonas/cirurgia , Infecções por Pseudomonas/etiologia , Diálise Renal , Estudos Retrospectivos , Resultado do Tratamento , Fatores de RiscoRESUMO
Purpose: Contact lens wear (CLW) is one of the leading risk factors for Pseudomonas aeruginosa keratitis (PAK). However, the intrinsic factors that contribute to the high susceptibility to keratitis during CLW remain to be elucidated. CLW over an extended period can elevate corneal norepinephrine (NE) concentration. In this study, we investigated the role of NE in promoting PAK. Methods: We constructed an injury-induced PAK model and a CLW-induced PAK model to confirm the impact of NE during corneal infection. Pharmacological blockage of NE and gene knockdown mouse were used to investigate the downstream effector of NE. RNA sequencing was performed to explore the cellular alterations during NE treatment. Non-parametric Mann-Whitney U test or Kruskal-Wallis test were used to ascertain the significance (P < 0.05). Results: Supplementation of NE led to PAK even without artificial corneal injury during CLW. The effect was mediated by the ß2-adrenergic receptor (ß2-AR) in the corneal epithelium. The ß2-AR blockage by the NE antagonist ICI118,551 (ICI) or by deleting of its encoding gene Adrb2 significantly alleviated infection during CLW. Conversely, ß2-AR activation compromised the integrity of the epithelium and significantly increased the cortical plaque marker ezrin. Transcriptome analysis identified that the protective effect of ICI on the keratitis was mediated by dual-specificity phosphatases. Suramin, a Dusp5 antagonist, abrogated the protective effect of ICI. Conclusions: These data reveal a new mechanism by which NE acts as an intrinsic factor that promotes CLW-induced PAK and provide novel therapeutic targets for treating keratitis by targeting NE-ß2-AR.
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Lentes de Contato , Ceratite , Infecções por Pseudomonas , Animais , Camundongos , Pseudomonas aeruginosa/fisiologia , Norepinefrina/farmacologia , Ceratite/etiologia , Lentes de Contato/efeitos adversos , Córnea , Infecções por Pseudomonas/etiologiaRESUMO
The severity and progression of lung disease are highly variable across individuals with cystic fibrosis (CF) and are imperfectly predicted by mutations in the human gene CFTR, lung microbiome variation or other clinical factors. The opportunistic pathogen Pseudomonas aeruginosa (Pa) dominates airway infections in most CF adults. Here we hypothesized that within-host genetic variation of Pa populations would be associated with lung disease severity. To quantify Pa genetic variation within CF sputum samples, we used deep amplicon sequencing (AmpliSeq) of 209 Pa genes previously associated with pathogenesis or adaptation to the CF lung. We trained machine learning models using Pa single nucleotide variants (SNVs), microbiome diversity data and clinical factors to classify lung disease severity at the time of sputum sampling, and to predict lung function decline after 5 years in a cohort of 54 adult CF patients with chronic Pa infection. Models using Pa SNVs alone classified lung disease severity with good sensitivity and specificity (area under the receiver operating characteristic curve: AUROC=0.87). Models were less predictive of lung function decline after 5 years (AUROC=0.74) but still significantly better than random. The addition of clinical data, but not sputum microbiome diversity data, yielded only modest improvements in classifying baseline lung function (AUROC=0.92) and predicting lung function decline (AUROC=0.79), suggesting that Pa AmpliSeq data account for most of the predictive value. Our work provides a proof of principle that Pa genetic variation in sputum tracks lung disease severity, moderately predicts lung function decline and could serve as a disease biomarker among CF patients with chronic Pa infections.
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Fibrose Cística , Infecções por Pseudomonas , Adulto , Humanos , Fibrose Cística/complicações , Pseudomonas aeruginosa/genética , Pulmão , Infecções por Pseudomonas/etiologia , Progressão da Doença , NucleotídeosRESUMO
Pseudomonas aeruginosa is one of the most important infectious pathogens in medicine. This bacterium causes various infections, especially in patients with severe burns and people with defective immune systems. The purpose of this study was to develop a nanovaccine based on PLGA nanoparticles and lipopolysaccharide and oligopolysaccharide antigens for appropriate stimulation of the humoral and cellular immune systems against P. aeruginosa. LPS-PLGA and OPS-PLGA conjugates were synthesized using the carbodiimide reaction. The prepared conjugates of as well as the pure antigens of LPS and OPS were injected to BALB/c mice in three periods at 2 week intervals. The ELISA test showed that the IgM, IgA, IgG, IgG1, IgG2b, IgG2a and IgG3 antibodies produced against LPS-PLGA or OPS-PLGA conjugates were tens of times higher than the pure antigens. Also, the opsonophagocytosis test showed that the performance and the effect of produced anti-LPS-PLGA antibodies were higher than other groups. In addition, the mice treated with LPS-PLGA conjugate were more resistant to P. aeruginosa infection than other groups. These findings indicated that LPS and OPS antigens in conjugation with PLGA nanoparticles have the ability to create and effective immunity against P. aeruginosa and LPS-PLGA is more effective than OPS-PLGA.
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Nanopartículas , Infecções por Pseudomonas , Camundongos , Animais , Pseudomonas aeruginosa , Lipopolissacarídeos , Imunoglobulina G , Camundongos Endogâmicos BALB C , Anticorpos Antibacterianos , Infecções por Pseudomonas/prevenção & controle , Infecções por Pseudomonas/etiologiaRESUMO
BACKGROUND: Pseudomonas aeruginosa accounts for 7 to 22 percent of breast implant-associated infections, which can result in reconstructive failures and explantation. Investigating host-pathogen-device interactions in mice and patient samples will improve the understanding of colonization mechanisms, for targeted treatments and clinical guidelines. METHODS: Mice with and without implants were infected with PAO1 laboratory strain or BIP2 or BIP16 clinical strains and killed at 1 day or 7 days after infection to evaluate for colonization of implants and underlying tissues by means of colony-forming unit enumeration. Immunostaining was performed on mouse implants, human tissue expanders colonized by BIP2, and acellular dermal matrix colonized by BIP16. RESULTS: Colonization of tissues and smooth implants by P. aeruginosa was strain-dependent: at 1 day after infection, all strains acutely infected tissues with and without implants with colonization levels reflecting growth rates of individual strains. At 7 days after infection, PAO1 caused colonization of approximately 10 5 colony-forming units/100 mg of tissue but required implant presence, whereas in mice infected with BIP2/BIP16, colony-forming units were below the limit of detection with or without implants. Immunofluorescence staining of mouse implants, however, demonstrated continued presence of BIP2 and BIP16. Staining showed co-localization of all strains with fibrinogen, collagen I, and collagen III on mouse and human samples. CONCLUSIONS: The trajectory of P. aeruginosa in breast implant-associated infections was strain-dependent, and strains could exhibit acute symptomatic or chronic asymptomatic colonization. With strains causing clinical symptoms, the presence of an implant significantly worsened infection. For asymptomatic colonizers, further studies investigating their long-term impacts, especially during periods of immunosuppression in hosts, are needed.
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Implante Mamário , Implantes de Mama , Mastite , Infecções por Pseudomonas , Animais , Implantes de Mama/efeitos adversos , Colágeno , Feminino , Humanos , Camundongos , Infecções por Pseudomonas/etiologia , Pseudomonas aeruginosaRESUMO
ABSTRACT: A 50-year-old patient who underwent secondary rhinoplasty 1 year after the operation presented with signs of localized infection on the postoperative twentieth day. An abscess due to Pseudomonas aeruginosa was detected in the nose and maxillary sinus. The infection regressed after surgical debridement combined with intravenous antibiotic therapy.Pseudomonas infection has been reported in only six patients after septorhinoplasty. Rhinoplasty was combined with other aesthetic procedures in three patients. The mean time of onset of complaints was 33.25 days. The most common complaint was pain. The mean time to complete regression of complaints after treatment was 44.5 days.Pseudomonas infection risk is especially increased in patients with combined surgical procedures and complicated revision rhinoplasty surgery. Careful examination of the patient, early and aggressive therapy, and surgical debridement are essential. The treatment of infection is incision and drainage of the affected areas. Antibiotic therapy followed by sensitivity-specific regimens should be administered."
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Infecções por Pseudomonas , Rinoplastia , Antibacterianos/uso terapêutico , Estética Dentária , Humanos , Pessoa de Meia-Idade , Septo Nasal/cirurgia , Nariz/cirurgia , Infecções por Pseudomonas/diagnóstico , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/etiologia , Rinoplastia/efeitos adversos , Rinoplastia/métodos , Resultado do TratamentoRESUMO
ABSTRACT: Infectious keratitis is a severe complication associated with contact lens (CL) wear, and can progress rapidly with suppurative infiltration, resulting in the loss of vision. Contact lens wearers with poor and improper care are susceptible to develop infectious keratitis. Gram-negative bacilli such as Pseudomonas aeruginosa, have an ability to form biofilms on CL cases and CLs. Moreover, P. aeruginosa has various virulence factors such as type III secretion system (TTSS) which is an important factor for pathogenicity in keratitis. The effector proteins of TTSS have been identified, namely ExoU, ExoS, ExoT, and ExoY. Pseudomonas aeruginosa strains with ExoU show resistance to disinfection. The strains isolated from CL-related keratitis have higher ExoU gene positivity. Expression of elastase and swarming motility of P. aeruginosa isolates significantly correlates with focus size of keratitis. In addition to education of lens care for the CL wearer, development of CL cleaning solutions targeting suppression of virulence factors are needed for prevention of CL-related keratitis in the future.
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Lentes de Contato , Ceratite , Infecções por Pseudomonas , Lentes de Contato/efeitos adversos , Humanos , Ceratite/etiologia , Infecções por Pseudomonas/etiologia , Pseudomonas aeruginosa , Fatores de Virulência/genéticaRESUMO
Remdesivir (RDV) reduces time to clinical improvement in hospitalized COVID -19 patients requiring supplemental oxygen. Dexamethasone improves survival in those requiring oxygen support. Data is lacking on the efficacy of combination therapy in patients on mechanical ventilation. We analyzed for comparative outcomes between Corticosteroid (CS) therapy with combined Corticosteroid and Remdesivir (CS-RDV) therapy. We conducted an observational cohort study of patients aged 18 to 90 with COVID-19 requiring ventilatory support using TriNetX (COVID-19 Research Network) between January 20, 2020, and February 9, 2021. We compared patients who received at least 48 hours of CS-RDV combination therapy to CS monotherapy. The primary outcome was 28-day all-cause mortality rates in propensity-matched (PSM) cohorts. Secondary outcomes were Length of Stay (LOS), Secondary Bacterial Infections (SBI), and MRSA (Methicillin-Resistant Staphylococcus aureus), and Pseudomonas infections. We used univariate and multivariate Cox proportional hazards models and stratified log-rank tests. Of 388 patients included, 91 (23.5%) received CS-RDV therapy, and 297 (76.5%) received CS monotherapy. After propensity score matching, with 74 patients in each cohort, all-cause mortality was 36.4% and 29.7% in the CS-RDV and CS therapy, respectively (P = 0.38). We used a Kaplan-Meier with a log-rank test on follow up period (P = 0.23), and a Hazards Ratio model (P = 0.26). SBI incidence was higher in the CS group (13.5% vs. 35.1%, P = 0.02) with a similar LOS (13.4 days vs. 13.4 days, P = 1.00) and similar incidence of MRSA/Pseudomonas infections (13.5% vs. 13.5%, P = 1.00) in both the groups. Therefore, CS-RDV therapy is non-inferior to CS therapy in reducing 28-day all-cause in-hospital mortality but associated with a significant decrease in the incidence of SBI in critically ill COVID-19 patients.
Assuntos
Monofosfato de Adenosina/análogos & derivados , Corticosteroides/uso terapêutico , Alanina/análogos & derivados , Tratamento Farmacológico da COVID-19 , Monofosfato de Adenosina/uso terapêutico , Idoso , Alanina/uso terapêutico , COVID-19/complicações , COVID-19/mortalidade , COVID-19/virologia , Estudos de Coortes , Quimioterapia Combinada , Feminino , Mortalidade Hospitalar , Humanos , Incidência , Estimativa de Kaplan-Meier , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Infecções por Pseudomonas/diagnóstico , Infecções por Pseudomonas/epidemiologia , Infecções por Pseudomonas/etiologia , Respiração Artificial , SARS-CoV-2/isolamento & purificação , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/etiologia , Resultado do TratamentoRESUMO
BACKGROUND: Mycotic aortic pseudoaneurysm is a rare complication after heart transplantation (HTX) with remarkable mortality. Intrathoracic infection is a well-documented predisposing factor for this disease. Staphylococcus aureus, Pseudomonas aeruginosa or Candida species are commonly isolated from resected specimens of the pseudoaneurysms. We demonstrate a unique case of mycotic pseudoaneurysm caused by presumably donor-derived Pseudomonas infection in a heart transplant recipient. CASE PRESENTATION: Our 67-year-old male patient treated with diabetes mellitus underwent HTX. The donor suffered from epiglottic abscess and pneumonia with known microorganisms including Pseudomonas, therefore both the donor and recipient received targeted antimicrobial therapy and prophylaxis. Five months after the uneventful HTX, lab test of the asymptomatic patient showed moderate, increasing C-reactive protein level without obviuos source of infection. Chest computed tomography showed a large (90 mm) saccular dilatation of the tubular portion of ascending aorta. Urgent surgical intervention identified a pseudoaneurysm, histological examinations and cultures of the resected aorta verified Pseudomonas aeruginosa aortitis, while all blood cultures remained negative. Retrospective interrogation of other transplanted organs of the donor supported donor-derived infection as the transport fluid of the right kidney grew Pseudomonas. The patient received 3 weeks of ceftazidime followed by 7 months of oral ciprofloxacin therapy. One year after the operation the patient was asymptomatic with normal inflammatory markers. CONCLUSIONS: Donor-derived infection is a rare but potential cause of aortitis. Early diagnosis, surgical intervention and adjuvant antibiotic therapy seem to be the keys to successful management of mycotic pseudoaneurysms after HTX.
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Falso Aneurisma , Aneurisma Infectado , Transplante de Coração , Infecções por Pseudomonas , Idoso , Falso Aneurisma/diagnóstico por imagem , Falso Aneurisma/etiologia , Aneurisma Infectado/diagnóstico por imagem , Aneurisma Infectado/etiologia , Aorta , Transplante de Coração/efeitos adversos , Humanos , Masculino , Infecções por Pseudomonas/diagnóstico , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/etiologia , Estudos RetrospectivosRESUMO
Pseudomonas aeruginosa is one of the principal pathogens implicated in respiratory infections of patients with cystic fibrosis (CF) and non-CF bronchiectasis. Previously, we demonstrated that impaired serum-mediated killing of P. aeruginosa was associated with increased severity of respiratory infections in patients with non-CF bronchiectasis. This inhibition was mediated by high titers of O-antigen-specific IgG2 antibodies that cloak the surface of the bacteria, blocking access to the membrane. Infection-related symptomatology was ameliorated in patients by using plasmapheresis to remove the offending antibodies. To determine if these inhibitory "cloaking antibodies" were prevalent in patients with CF, we investigated 70 serum samples from patients with P. aeruginosa infection and 5 from those without P. aeruginosa infection. Of these patients, 32% had serum that inhibited the ability of healthy control serum to kill P. aeruginosa. Here, we demonstrate that this inhibition of killing requires O-antigen expression. Furthermore, we reveal that while IgG alone can inhibit the activity of healthy control serum, O-antigen-specific IgA in patient sera can also inhibit serum-killing. We found that antibody affinity, not just titer, was also important in the inhibition of serum-mediated killing. These studies provide novel insight into cloaking antibodies in human infection and may provide further options in CF and other diseases for treatment of recalcitrant P. aeruginosa infections.
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Anticorpos Antibacterianos/imunologia , Fibrose Cística/complicações , Imunoglobulina A/imunologia , Imunoglobulina G/imunologia , Lipopolissacarídeos/imunologia , Infecções por Pseudomonas/etiologia , Pseudomonas aeruginosa/imunologia , Proteínas do Sistema Complemento/imunologia , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangueRESUMO
We present a case of an 80-year-old male who developed skull base osteomyelitis after nasopharyngeal cyst removal. A review of the literature regarding complications after nasopharyngeal cyst removal was performed. We describe the difficulty of diagnosing an osteomyelitis infection and the best approach to recognizing osteomyelitis before complications worsen.
Assuntos
Cistos/cirurgia , Doenças Nasofaríngeas/cirurgia , Osteomielite/etiologia , Infecções por Pseudomonas/etiologia , Base do Crânio , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Humanos , Masculino , Osteomielite/tratamento farmacológico , Osteomielite/microbiologia , Complicações Pós-Operatórias , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosaRESUMO
BACKGROUND: In Cystic Fibrosis (CF) airways, the dehydrated, thick mucus promotes the establishment of persistent polymicrobial infections and drives chronic airways inflammation. This also predisposes the airways to further infections, the vicious, self-perpetuating cycle causing lung damage and progressive lung function decline. The airways are a poly-microbial environment, containing both aerobic and anaerobic bacterial species. Pseudomonas aeruginosa (P. aeruginosa) infections contribute to the excessive inflammatory response in CF, but the role of anaerobic Prevotella spp., frequently found in CF airways, is not known. MATERIALS: We assessed innate immune signalling in CF airway epithelial cells in response to clinical strains of P. histicola, P. nigresens and P. aeruginosa. CFBE41o- cells were infected with P. aeruginosa (MOI 100, 2h) followed by infection with P. histicola or P. nigrescens (MOI 100, 2h). Cells were incubated under anaerobic conditions for the duration of the experiments. RESULTS: Our study shows that P. histicola and P. nigresens can reduce the growth of P. aeruginosa and dampen the inflammatory response in airway epithelial cells. We specifically illustrate that the presence of the investigated Prevotella spp. reduces Toll-like-receptor (TLR)-4, MAPK, NF-κB(p65) signalling and cytokine release (Interleukin (IL)-6, IL-8) in mixed infections. CONCLUSION: Our work, for the first time, strongly indicates a relationship between P. aeruginosa and anaerobic Prevotella spp.. The observed modified NF-κB and MAPK signalling indicates some mechanisms underlying this interaction that could offer a novel therapeutic approach to combat chronic P. aeruginosa infection in people with CF.
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Brônquios/citologia , Brônquios/microbiologia , Fibrose Cística/complicações , Fibrose Cística/microbiologia , Células Epiteliais/imunologia , Inflamação/etiologia , Inflamação/microbiologia , Prevotella/fisiologia , Infecções por Pseudomonas/etiologia , Pseudomonas aeruginosa/fisiologia , Mucosa Respiratória/citologia , Mucosa Respiratória/microbiologia , Células Cultivadas , Fibrose Cística/imunologia , HumanosAssuntos
Fibrose Cística , Infecções por Pseudomonas , Infecções Respiratórias , Antibacterianos/uso terapêutico , Criança , Fibrose Cística/complicações , Fibrose Cística/terapia , Humanos , Pulmão/diagnóstico por imagem , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/etiologia , Pseudomonas aeruginosaRESUMO
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.
Assuntos
Proteínas de Bactérias/metabolismo , Estado Terminal , Unidades de Terapia Intensiva/estatística & dados numéricos , Pulmão , Metaloendopeptidases/metabolismo , Mortalidade , Pneumonia Bacteriana , Infecções por Pseudomonas , Pseudomonas aeruginosa , Animais , Correlação de Dados , Estado Terminal/mortalidade , Estado Terminal/terapia , Demografia , Modelos Animais de Doenças , Feminino , Humanos , Pulmão/imunologia , Pulmão/microbiologia , Masculino , Camundongos , Pessoa de Meia-Idade , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/mortalidade , Infecções por Pseudomonas/etiologia , Infecções por Pseudomonas/mortalidade , Pseudomonas aeruginosa/enzimologia , Pseudomonas aeruginosa/isolamento & purificação , Pseudomonas aeruginosa/patogenicidade , Respiração Artificial/estatística & dados numéricos , Estados Unidos/epidemiologia , Fatores de VirulênciaRESUMO
The Liverpool epidemic strain (LES) is an important transmissible clonal lineage of Pseudomonas aeruginosa that chronically infects the lungs of people with cystic fibrosis (CF). Previous studies have focused on the genomics of the LES in a limited number of isolates, mostly from one CF centre in the UK, and from studies highlighting identification of the LES in Canada. Here we significantly extend the current LES genome database by genome sequencing 91 isolates from multiple CF centres across the UK, and we describe the comparative genomics of this large collection of LES isolates from the UK and Canada. Phylogenetic analysis revealed that the 145 LES genomes analysed formed a distinct clonal lineage when compared with the wider P. aeruginosa population. Notably, the isolates formed two clades: one associated with isolates from Canada, and the other associated with UK isolates. Further analysis of the UK LES isolates revealed clustering by clinic geography. Where isolates clustered closely together, the association was often supported by clinical data linking isolates or patients. When compared with the earliest known isolate, LESB58 (from 1988), many UK LES isolates shared common loss-of-function mutations, such as in genes gltR and fleR. Other loss-of-function mutations identified in previous studies as common adaptations during CF chronic lung infections were also identified in multiple LES isolates. Analysis of the LES accessory genome (including genomic islands and prophages) revealed variations in the carriage of large genomic regions, with some evidence for shared genomic island/prophage complement according to clinic location. Our study reveals divergence and adaptation during the spread of the LES, within the UK and between continents.
Assuntos
Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/transmissão , Pseudomonas aeruginosa/isolamento & purificação , Adaptação Fisiológica , Canadá , Fibrose Cística/complicações , Epidemias , Genoma Bacteriano , Humanos , Pulmão/microbiologia , Infecções Oportunistas/microbiologia , Infecções Oportunistas/transmissão , Filogenia , Infecções por Pseudomonas/etiologia , Pseudomonas aeruginosa/classificação , Pseudomonas aeruginosa/fisiologia , Reino Unido/epidemiologiaRESUMO
Background:Pseudomonas aeruginosa (PA) infection in cystic fibrosis (CF) is associated with poor prognosis. Surfactant protein-D (SFTPD) and mannose-binding lectin (MBL) play a critical role in innate immunity and response to bacterial infections. We investigated serum levels and genetic variants of SFTPD and MBL in CF patients. Method: Thirty-five Caucasian patients homozygous for ΔF508del were genotyped for functional relevant polymorphisms within MBL2 (promoter-221 Y/X, codons 52, 54, and 57) and SFTPD genes (Met11Thr, Ala160Thr, and Ser270Thr). Serum levels of collectins, clinical characteristics, and PA status were correlated with genetic data. Results: Patients age, gender, and PA status did not affect MBL and SFTPD serum concentrations. MBL concentrations were correlated with MBL haplotypes. Patients with chronic Pseudomonas aeroginosa infection (PAC) and MBL insufficiency had a shorter interval between first PA infection and onset of PAC (0.01 vs. 4.6 years, p < 0.04) as well as a lower median age at transition to PAC (9.8 vs. 16.4 years, p < 0.03) compared to MBL sufficient patients with PAC. SFTPD serum level and FEV1% (Spearman r = -0.41, p < 0.03) showed a negative correlation irrespective of PA infection status. The hazard ratio to PA acquisition was increased in carriers of the SFTPD haplotype 11Thr-160Ala-270Ser compared to carriers of the common 11Met-160Thr-270Ser haplotype [HR 3.0 (95%CI: 1.1-8.6), p < 0.04]. Conclusion: MBL insufficiency leads to a shorter interval between first PA infection and onset of chronic infection. Susceptibility to PA acquisition is associated with SFTPD genetic variants with 11Thr-160Ala-270Ser as risk haplotype for early PA infection. This may be due to presence of threonine associated with oligomeric structure of SFTPD and binding ability to bacteria.