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BACKGROUND: Cryptococcal osteomyelitis is a rare and potentially serious condition, typically encountered in individuals with compromised immune systems. This case underscores the unusual occurrence of disseminated Cryptococcosis in an immunocompetent person, involving multiple bones and lungs, with Cryptococcus neoformans identified as the causative agent. CASE PRESENTATION: An Indonesian man, previously in good health, presented with a chief complaint of successive multiple bone pain lasting for more one month, without any prior history of trauma. Additionally, he reported a recent onset of fever. On physical examination, tenderness was observed in the left lateral chest wall and right iliac crest. Laboratory findings indicated mildly elevated inflammatory markers. A computed tomography (CT) scan of the chest revealed an ovoid solid nodule in the right lower lung and multifocal osteolytic lesions in the sternum, ribs, and humeral head. A magnetic resonance imaging (MRI) study of the sacrum showed multiple lesions in the bilateral iliac bone and the lower L4 vertebral body. Confirmation of Cryptococcal osteomyelitis involved a fine-needle biopsy and culture, identifying Cryptococcus neoformans in the aspirate. The patient responded positively to targeted antifungal treatments, leading to a gradual improvement in his condition. CONCLUSIONS: This case emphasizes the need to consider Cryptococcus neoformans osteomyelitis in immunocompetent patients with bone pain. A definitive diagnosis involves a fine-needle biopsy for pathology and culture, and prompt initiation of appropriate antifungal treatment has proven effective in preventing mortality.
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Criptococosis , Cryptococcus neoformans , Osteomielitis , Masculino , Humanos , Antifúngicos/uso terapéutico , Criptococosis/diagnóstico , Criptococosis/tratamiento farmacológico , Pulmón , Osteomielitis/diagnóstico , Osteomielitis/tratamiento farmacológico , DolorRESUMEN
Emerging evidence highlights the role of non-coding small RNAs in host-influenza interaction. We have identified a Y RNA-derived small RNA, miR-1975, which is upregulated upon influenza A virus infection in A549 cells. The aim of this study is to investigate whether miR-1975 serves as an indicator of clinical severity upon influenza infection. We investigate the abundance of miR-1975 in sera from clinical patients and its correlation with hypoxemia status. We quantified its amounts in sera from influenza virus-infected patients and healthy volunteers by means of stem-loop RT-PCR. Median values of miR-1975 were significantly higher in influenza virus-infected patients, especially in hypoxemic patients. miR-1975 levels at the acute stage of the disease were highly correlated with the fraction of inspired oxygen used by the patients and total ventilator days. Receiver operator characteristic curve analysis revealed that miR-1975 levels in combination with days of fever before presenting to hospital had significant predictive value for hypoxemia and respiratory failure for patients infected with influenza virus. Our results reveal that circulating miR-1975 has great potential to serve as a biomarker for predicting prognosis in patients infected with influenza virus.
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Subtipo H1N1 del Virus de la Influenza A/genética , Gripe Humana/virología , Adulto , Femenino , Humanos , Gripe Humana/sangre , Masculino , MicroARNs/análisis , Persona de Mediana Edad , Curva ROC , Reacción en Cadena en Tiempo Real de la Polimerasa , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
BACKGROUND: Multiple interplays between viral and host factors are involved in influenza virus replication and pathogenesis. Several small RNAs have recently emerged as important regulators of host response to viral infections. The aim of this study was to characterize the functional role of hsa-miR-1975, a Y5 RNA-derived small RNA, in defending influenza virus and delineate the mechanisms. METHODS: We performed high throughput sequencing of small RNAs in influenza virus-infected cells to identify up- or down- regulated small RNA species. The expression of the most abundant RNA species (hsa-miR-1975) was validated by stem-loop reverse transcription-polymerase chain reaction (RT-PCR). Antiviral effects of hsa-miR-1975 were confirmed by Western Blot, RT-PCR and plaque assay. In vitro perturbation of hsa-miR-1975 combined with exosomes isolation was used to elucidate the role and mechanism of hsa-miR-1975 in the context of antiviral immunity. RESULTS: Small RNA sequencing revealed that hsa-miR-1975 was the most up-regulated small RNA in influenza virus-infected cells. The amount of intracellular hsa-miR-1975 increased in the late stage of the influenza virus replication cycle. The increased hsa-miR-1975 was at least partially derived from degradation of Y5RNA as a result of cellular apoptosis. Unexpectedly, hsa-miR-1975 mimics inhibited influenza virus replication while hsa-miR-1975 sponges enhanced the virus replication. Moreover, hsa-miR-1975 was secreted in exosomes and taken up by the neighboring cells to induce interferon expression. CONCLUSIONS: Our findings unravel a critical role of Y-class small RNA in host's defense against influenza virus infection and reveal its antiviral mechanism through exosome delivery. This may provide a new candidate for targeting influenza virus.
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Exosomas/fisiología , Subtipo H1N1 del Virus de la Influenza A/fisiología , Subtipo H3N2 del Virus de la Influenza A/fisiología , MicroARNs/fisiología , Replicación Viral , Células A549 , Animales , Perros , Humanos , Células de Riñón Canino Madin Darby , MicroARNs/genéticaRESUMEN
Breakthrough Acinetobacter bacteremia during carbapenem therapy is not uncommon, and it creates therapeutic dilemmas for clinicians. This study was conducted to evaluate the clinical and microbiological characteristics of breakthrough Acinetobacter bacteremia during carbapenem therapy and to assess the efficacy of various antimicrobial therapies. We analyzed 100 adults who developed breakthrough Acinetobacter bacteremia during carbapenem therapy at 4 medical centers over a 6-year period. Their 30-day mortality rate was 57.0%, and the carbapenem resistance rate of their isolates was 87.0%. Among patients with carbapenem-resistant Acinetobacter bacteremia, breakthrough bacteremia during carbapenem therapy was associated with a significantly higher 14-day mortality (51.7% versus 37.4%, respectively; P = 0.025 by bivariate analysis) and a higher 30-day mortality (P = 0.037 by log rank test of survival analysis) than in the nonbreakthrough group. For the treatment of breakthrough Acinetobacter bacteremia during carbapenem therapy, tigecycline-based therapy was associated with a significantly higher 30-day mortality (80.0%) than those with continued carbapenem therapy (52.5%) and colistin-based therapy (57.9%) by survival analysis (P = 0.047 and 0.045 by log rank test, respectively). Cox regression controlling for confounders, including severity of illness indices, demonstrated that treatment with tigecycline-based therapy for breakthrough Acinetobacter bacteremia was an independent predictor of 30-day mortality (hazard ratio, 3.659; 95% confidence interval, 1.794 to 7.465; P < 0.001). Patients with breakthrough Acinetobacter bacteremia during carbapenem therapy posed a high mortality rate. Tigecycline should be used cautiously for the treatment of breakthrough Acinetobacter bacteremia that develops during carbapenem therapy.
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Infecciones por Acinetobacter/tratamiento farmacológico , Acinetobacter baumannii/efectos de los fármacos , Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Carbapenémicos/uso terapéutico , Infecciones por Acinetobacter/microbiología , Infecciones por Acinetobacter/mortalidad , Acinetobacter baumannii/aislamiento & purificación , Anciano , Anciano de 80 o más Años , Bacteriemia/microbiología , Bacteriemia/mortalidad , Comorbilidad , Infección Hospitalaria/tratamiento farmacológico , Infección Hospitalaria/microbiología , Infección Hospitalaria/mortalidad , Farmacorresistencia Bacteriana Múltiple , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
The Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) offer different recommendations for carbapenem MIC susceptibility breakpoints for Acinetobacter species. In addition, the clinical efficacy of the intermediate category remains uncertain. This study was designed to determine the optimal predictive breakpoints based on the survival of patients with Acinetobacter bacteremia treated with a carbapenem. We analyzed the 30-day mortality rates of 224 adults who received initial carbapenem monotherapy for the treatment of Acinetobacter bacteremia at 4 medical centers over a 5-year period, according to the carbapenem MICs of the initial isolates. The 30-day mortality was about 2-fold greater in patients whose isolates had carbapenem MICs of ≥8 mg/liter than in those with isolates with MICs of ≤4 mg/liter. The differences were significant by bivariate analysis (53.1% [60/113] versus 25.2% [28/111], respectively; P < 0.001) and on survival analysis by the log rank test (P < 0.001). Classification and regression tree analysis revealed a split between MICs of 4 and 8 mg/liter and predicted the same difference in mortality, with a P value of <0.001. Carbapenem treatment for Acinetobacter bacteremia caused by isolates with carbapenem MICs of ≥8 mg/liter was an independent predictor of 30-day mortality (odds ratio, 4.218; 95% confidence interval, 2.213 to 8.039; P < 0.001). This study revealed that patients with Acinetobacter bacteremia treated with a carbapenem had a more favorable outcome when the carbapenem MICs of their isolates were ≤4 mg/liter than those with MICs of ≥8 mg/liter.
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Infecciones por Acinetobacter/tratamiento farmacológico , Acinetobacter baumannii/efectos de los fármacos , Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Carbapenémicos/uso terapéutico , Infecciones por Acinetobacter/microbiología , Infecciones por Acinetobacter/mortalidad , Acinetobacter baumannii/aislamiento & purificación , Anciano , Anciano de 80 o más Años , Bacteriemia/microbiología , Bacteriemia/mortalidad , Infección Hospitalaria/tratamiento farmacológico , Infección Hospitalaria/microbiología , Farmacorresistencia Bacteriana Múltiple , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: Whether antituberculosis (anti-TB) treatment in patients with chronic viral hepatitis affects the incidence and onset time of drug-induced hepatotoxicity (DIH) is still controversial. The aim of this retrospective study was to find out whether chronic viral hepatitis affects the incidence and onset time of DIH. METHODS: All patients diagnosed with active TB and being treated at a tertiary referral hospital between 2002 and 2009 were identified from medical records, from which 553 patients were enrolled in the study. The incidence and onset of DIH in patients with and without chronic viral hepatitis (controls) were compared. RESULTS: The incidence of DIH was similar in patients with and without chronic hepatitis (8 % [32/392] vs. 7 % [11/161], P > 0.05). The incidence of transient liver function impairment (TLI) was significantly lower in controls than in chronic hepatitis patients (2 % [9/392] vs. 12 % [20/161], P < 0.001. The mean onset times of DIH in the control, hepatitis B virus (HBV), and hepatitis C virus (HCV) groups were not significantly different (40, 39, and 67 days, respectively, all P > 0.05). The mean onset times of TLI in the control, HBV, and HCV groups were significantly different (23, 48, and 68 days, respectively, all P < 0.05). CONCLUSIONS: Liver function impairment during anti-TB therapy in patients with chronic viral hepatitis was due to mostly TLI, with TLI occurring later than in controls. Chronic viral hepatitis had no significant effect on the incidence of DIH.
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Antituberculosos/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/epidemiología , Coinfección , Hepatitis B Crónica/complicaciones , Hepatitis C Crónica/complicaciones , Tuberculosis/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Enfermedad Hepática Inducida por Sustancias y Drogas/diagnóstico , Femenino , Hepatitis B Crónica/diagnóstico , Hepatitis C Crónica/diagnóstico , Humanos , Incidencia , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Taiwán/epidemiología , Centros de Atención Terciaria , Factores de Tiempo , Tuberculosis/complicaciones , Tuberculosis/diagnósticoRESUMEN
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of the Coronavirus disease-19 (COVID-19) pandemic, utilizes angiotensin-converting enzyme 2 (ACE2) as a receptor for virus infection. However, the expression pattern of ACE2 does not coincide with the tissue tropism of SARS-CoV-2, hinting that other host proteins might be involved in facilitating SARS-CoV-2 entry. To explore potential host factors for SARS-CoV-2 entry, we performed an arrayed shRNA screen in H1650 and HEK293T cells. Here, we identified a disintegrin and a metalloproteinase domain 9 (ADAM9) protein as an important host factor for SARS-CoV-2 entry. Our data showed that silencing ADAM9 reduced virus entry, while its overexpression promoted infection. The knockdown of ADAM9 decreased the infectivity of the variants of concern tested-B.1.1.7 (alpha), B.1.617.2 (delta), and B.1.1.529 (omicron). Furthermore, mechanistic studies indicated that ADAM9 is involved in the binding and endocytosis stages of SARS-CoV-2 entry. Through immunoprecipitation experiments, we demonstrated that ADAM9 binds to the S1 subunit of the SARS-CoV-2 Spike. Additionally, ADAM9 can interact with ACE2, and co-expression of both proteins markedly enhances virus infection. Moreover, the enzymatic activity of ADAM9 facilitates virus entry. Our study reveals an insight into the mechanism of SARS-CoV-2 virus entry and elucidates the role of ADAM9 in virus infection. IMPORTANCE COVID-19, an infectious respiratory disease caused by SARS-CoV-2, has greatly impacted global public health and the economy. Extensive vaccination efforts have been launched worldwide over the last couple of years. However, several variants of concern that reduce the efficacy of vaccines have kept emerging. Thereby, further understanding of the mechanism of SARS-CoV-2 entry is indispensable, which will allow the development of an effective antiviral strategy. Here, we identify a disintegrin and metalloproteinase domain 9 (ADAM9) protein as a co-factor of ACE2 important for SARS-CoV-2 entry, even for the variants of concern, and show that ADAM9 interacts with Spike to aid virus entry. This virus-host interaction could be exploited to develop novel therapeutics against COVID-19.
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In the past decades, due to the high prevalence of the antibiotic-resistant isolates of Acinetobacter baumannii, it has emerged as one of the most troublesome pathogens threatening the global healthcare system. Furthermore, this pathogen has the ability to form biofilms, which is another effective mechanism by which it survives in the presence of antibiotics. However, the clinical impact of biofilm-forming A. baumannii isolates on patients with bacteremia is largely unknown. This retrospective study was conducted at five medical centers in Taiwan over a 9-year period. A total of 252 and 459 patients with bacteremia caused by biofilm- and non-biofilm-forming isolates of A. baumannii, respectively, were enrolled. The clinical demographics, antimicrobial susceptibility, biofilm-forming ability, and patient clinical outcomes were analyzed. The biofilm-forming ability of the isolates was assessed using a microtiter plate assay. Multivariate analysis revealed the higher APACHE II score, shock status, lack of appropriate antimicrobial therapy, and carbapenem resistance of the infected strain were independent risk factors of 28-day mortality in the patients with A. baumannii bacteremia. However, there was no significant difference between the 28-day survival and non-survival groups, in terms of the biofilm forming ability. Compared to the patients infected with non-biofilm-forming isolates, those infected with biofilm-forming isolates had a lower in-hospital mortality rate. Patients with either congestive heart failure, underlying hematological malignancy, or chemotherapy recipients were more likely to become infected with the biofilm-forming isolates. Multivariate analysis showed congestive heart failure was an independent risk factor of infection with biofilm-forming isolates, while those with arterial lines tended to be infected with non-biofilm-forming isolates. There were no significant differences in the sources of infection between the biofilm-forming and non-biofilm-forming isolate groups. Carbapenem susceptibility was also similar between these groups. In conclusion, the patients infected with the biofilm-forming isolates of the A. baumannii exhibited different clinical features than those infected with non-biofilm-forming isolates. The biofilm-forming ability of A. baumannii may also influence the antibiotic susceptibility of its isolates. However, it was not an independent risk factor for a 28-day mortality in the patients with bacteremia.
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Infecciones por Acinetobacter , Acinetobacter baumannii , Bacteriemia , Insuficiencia Cardíaca , Infecciones por Acinetobacter/tratamiento farmacológico , Infecciones por Acinetobacter/epidemiología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Biopelículas , Carbapenémicos/uso terapéutico , Humanos , Pruebas de Sensibilidad Microbiana , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Carbapenem-resistant Acinetobacter species have emerged as notorious pathogens causing nosocomial infections. Several phenotypic methods have been developed for detecting carbapenemase production in Enterobacteriaceae. The accuracy of these methods in the prediction of carbapenemase production in Acinetobacter species has not been studied well. METHODS: This retrospective study enrolled adult patients with Acinetobacter bacteremia from four medical centers in Taiwan between 2012 and 2016. Their demographics and clinical outcomes were recorded. The carbapenem susceptibility of the Acinetobacter species was determined using the agar diffusion method. The carbapenemase genes were detected by PCR. Four phenotypic methods, including the modified Hodge test (MHT), modified carbapenem inactivation method (mCIM), Carba NP test, and CarbAcineto NP test were carried out to determine the production of carbapenemase. RESULTS: We analyzed 257 adults who received initial carbapenem monotherapy for the treatment of Acinetobacter bacteremia. Shock within three days of bacteremia and acquisition of carbapenem non-susceptible isolates were independently associated with a higher 14-day and 30-day mortality in patients with Acinetobacter bacteremia. Among the four phenotypic tests for carbapenemase detection, MHT using the imipenem disc displayed the greatest sensitivity (94%; 95% confidence interval [CI], 89-97%) and specificity (81%; 95% CI, 73-88%) for predicting imipenem non-susceptibility. CONCLUSION: Carbapenem non-susceptibility and shock were independent risk factors for mortality in patients with Acinetobacter bacteremia. The MHT could predict the carbapenem susceptibility of Acinetobacter isolates. It is a cheap and quick assay, which could be applied in clinical practice.
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Acinetobacter , Bacteriemia , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Proteínas Bacterianas/análisis , Proteínas Bacterianas/genética , Carbapenémicos/farmacología , Carbapenémicos/uso terapéutico , Humanos , Imipenem , Pruebas de Sensibilidad Microbiana , Estudios Retrospectivos , beta-Lactamasas/genéticaRESUMEN
Anti-interferon (IFN)-γ autoantibodies (AIGAs) are a pathogenic factor in late-onset immunodeficiency with disseminated mycobacterial and other opportunistic infections. AIGAs block IFN-γ function, but their effects on IFN-γ signaling are unknown. Using a single-cell capture method, we isolated 19 IFN-γ-reactive monoclonal antibodies (mAbs) from patients with AIGAs. All displayed high-affinity (KD < 10-9 M) binding to IFN-γ, but only eight neutralized IFN-γ-STAT1 signaling and HLA-DR expression. Signal blockade and binding affinity were correlated and attributed to somatic hypermutations. Cross-competition assays identified three nonoverlapping binding sites (I-III) for AIGAs on IFN-γ. We found that site I mAb neutralized IFN-γ by blocking its binding to IFN-γR1. Site II and III mAbs bound the receptor-bound IFN-γ on the cell surface, abolishing IFN-γR1-IFN-γR2 heterodimerization and preventing downstream signaling. Site III mAbs mediated antibody-dependent cellular cytotoxicity, probably through antibody-IFN-γ complexes on cells. Pathogenic AIGAs underlie mycobacterial infections by the dual blockade of IFN-γ signaling and by eliminating IFN-γ-responsive cells.
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Infecciones por Mycobacterium , Receptores de Interferón , Anticuerpos Monoclonales , Autoanticuerpos , Impedancia Eléctrica , Humanos , Interferón gamma , Infecciones por Mycobacterium/genética , Infecciones por Mycobacterium/microbiología , Receptores de Interferón/genéticaRESUMEN
BACKGROUND: The impact of appropriate antimicrobial therapy for A. baumannii bacteremic pneumonia has not been well established due to the inclusion of the three phenotypically indistinguishable Acinetobacter species and confounding factors including underlying diseases and severity of infection. This retrospective study aimed to evaluate the impact of appropriate antimicrobial therapy on 14-day mortality in A. baumannii bacteremic pneumonia patients after adjusting for risk factors. METHODS: This study was conducted at five medical centers in Taiwan between July 2012 and June 2016. A. baumannii species identification was performed using reference molecular methods. Risk factors for 14-day mortality were analyzed via logistic regression. The interaction between the Acute Physiology and Chronic Health Evaluation (APACHE) II score and appropriate antimicrobial therapy was assessed using the logistic model. RESULTS: A total of 336 patients with monomicrobial A. baumannii bacteremic pneumonia were included in this study. The overall 14-day mortality rate was 47.3%. The crude mortality of appropriate antimicrobial therapy was 35.9% (57 of 151 patients). Appropriate antimicrobial therapy was associated with a lower mortality after multivariate adjustment (odds ratio [OR], 0.57; 95% confidence interval [CI], 0.34-0.97; p = 0.04), and the effect was influenced by APACHE II score (OR for interaction term, 0.0098; 95% CI, 0.0005-0.1885; p = 0.002). Further analysis demonstrated that appropriate antimicrobial therapy significantly reduced 14-day mortality among the patients with an APACHE II score > 35 (OR 0.0098; 95% CI 0.0005-0.1885). CONCLUSION: Appropriate antimicrobial therapy decreases 14-day mortality of the most severely ill patients with A. baumannii bacteremic pneumonia.
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Infecciones por Acinetobacter/mortalidad , Acinetobacter baumannii/aislamiento & purificación , Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Neumonía/tratamiento farmacológico , Infecciones por Acinetobacter/tratamiento farmacológico , Acinetobacter baumannii/efectos de los fármacos , Acinetobacter baumannii/genética , Anciano , Antibacterianos/farmacología , Bacteriemia/microbiología , Bacteriemia/mortalidad , Femenino , Humanos , Modelos Logísticos , Masculino , Mortalidad , Análisis Multivariante , Neumonía/microbiología , Neumonía/mortalidad , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Clinical characteristics and risk factors for mortality of Acinetobacter bacteremia in cirrhotic patients have not been investigated. METHODS: Acinetobacter bacteremia cases from four medical centers were collected from 2009 to 2014, to compare between patients with and without liver cirrhosis. Risk factors for mortality of Acinetobacter bacteremia among cirrhotic patients were identified using multivariate logistic regression. RESULTS: Among the patients with Acinetobacter bacteremia, 72 had liver cirrhosis and 816 had not. Patients with cirrhosis were younger (57.5 [50-71] vs. 72 [50.25-71], p < 0.001), had more solid tumor (51.4% vs. 31.4%, p = 0.001), lower Acute Physiology and Chronic Health Evaluation II (APACHE II) scores (17 [12-24] vs. 20 [13-28], p = 0.012), less sourced from pneumonia (19.4% vs. 35.8%, p = 0.008), and less caused by Acinetobacterbaumannii (33.3% vs. 50.6%, p = 0.007) than those without. After matching for age, sex, and causative pathogens, the 30-day mortality (34.7% vs. 29.2%, p = 0.592) and APACHE II scores (17 vs. 17, p = 0.769) were not significant. APACHE II score (odds ratio [OR], 1.146; 95% confidence interval [CI], 1.035-1.268; p = 0.009), bacteremia caused by A. baumannii (OR, 20.501; 95% CI, 2.301-182.649; p = 0.007), and solid tumor (OR, 18.073; 95% CI, 1.938-168.504; p = 0.011) were independent risk factors for 30-day mortality of cirrhotic patients with Acinetobacter bacteremia. CONCLUSION: Even though cirrhotic patients with Acinetobacter bacteremia were younger and had lower APACHE II scores than non-cirrhotic patients, the mortality rates were insignificantly different between the two groups.
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Infecciones por Acinetobacter/mortalidad , Bacteriemia/microbiología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/microbiología , APACHE , Infecciones por Acinetobacter/complicaciones , Acinetobacter baumannii , Anciano , Anciano de 80 o más Años , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , TaiwánAsunto(s)
Antibacterianos , Infecciones por Pseudomonas , Humanos , Antibacterianos/farmacología , Meropenem/farmacología , Pseudomonas aeruginosa , Taiwán/epidemiología , Farmacorresistencia Bacteriana , Imipenem/farmacología , Pruebas de Sensibilidad Microbiana , Infecciones por Pseudomonas/tratamiento farmacológico , beta-LactamasasRESUMEN
The higher 14-day mortality rate for patients with Acinetobacter bacteremia receiving tigecycline appropriately compared to other appropriate antibiotics (36.4% versus 14.2%, P = 0.028) was due to the poor effect of tigecycline for isolates with a minimum inhibitory concentration of 2 µg/mL (63.6% of 11 versus 14.2% of 127, P = 0.001).
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Infecciones por Acinetobacter/tratamiento farmacológico , Infecciones por Acinetobacter/microbiología , Acinetobacter/efectos de los fármacos , Bacteriemia/tratamiento farmacológico , Minociclina/análogos & derivados , Acinetobacter/aislamiento & purificación , Infecciones por Acinetobacter/mortalidad , Infecciones por Acinetobacter/fisiopatología , Acinetobacter baumannii/efectos de los fármacos , Acinetobacter calcoaceticus/efectos de los fármacos , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Bacteriemia/microbiología , Bacteriemia/mortalidad , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Minociclina/uso terapéutico , Mortalidad , Estudios Prospectivos , Estudios Retrospectivos , Taiwán , Tigeciclina , Resultado del TratamientoRESUMEN
The effect of biofilm formation on bacteraemic pneumonia caused by A. baumannii is unknown. We conducted a 4-year multi-center retrospective study to analyze 71 and 202 patients with A. baumannii bacteraemic pneumonia caused by biofilm-forming and non-biofilm-forming isolates, respectively. The clinical features and outcomes of patients were investigated. Biofilm formation was determined by a microtitre plate assay. The antimicrobial susceptibilities of biofilm-associated cells were assessed using the minimum biofilm eradication concentration (MBEC) assay. Whole-genome sequencing was conducted to identify biofilm-associated genes and their promoters. Quantitative reverse transcription polymerase chain reaction was performed to confirm the expression difference of biofilm-associated genes. There was no significant difference in the clinical characteristics or the outcomes between patients infected with biofilm-forming and non-biofilm-forming strains. Compared with non-biofilm-forming isolates, biofilm-forming isolates exhibited lower resistance to most antimicrobials tested, including imipenem, meropenem, ceftazidime, ciprofloxacin and gentamicin; however, the MBEC assay confirmed the increased antibiotic resistance of the biofilm-embedded bacteria. Biofilm-associated genes and their promoters were detected in most isolates, including the non-biofilm-forming strains. Biofilm-forming isolates showed higher levels of expression of the biofilm-associated genes than non-biofilm-forming isolates. The biofilm-forming ability of A. baumannii isolates might not be associated with worse outcomes in patients with bacteraemic pneumonia.
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Infecciones por Acinetobacter/tratamiento farmacológico , Proteínas Bacterianas/genética , Biopelículas/efectos de los fármacos , Neumonía/tratamiento farmacológico , Infecciones por Acinetobacter/genética , Infecciones por Acinetobacter/microbiología , Infecciones por Acinetobacter/patología , Acinetobacter baumannii/efectos de los fármacos , Acinetobacter baumannii/genética , Acinetobacter baumannii/patogenicidad , Antibacterianos/administración & dosificación , Biopelículas/crecimiento & desarrollo , Ciprofloxacina/administración & dosificación , Farmacorresistencia Bacteriana Múltiple , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Meropenem/administración & dosificación , Pruebas de Sensibilidad Microbiana , Neumonía/genética , Neumonía/microbiología , Neumonía/patología , Estudios RetrospectivosRESUMEN
BACKGROUND/PURPOSE: Patients with Acinetobacter pittii and Acinetobacter nosocomialis bacteremia have lower mortality rates than those with Acinetobacter baumannii bacteremia. However, it is unknown whether these organisms differ in outcomes of bacteremic patients. We conducted this study to answer this question. METHODS: In this retrospective study conducted at a teaching hospital in Taiwan, we enrolled all 86 patients who had developed A. pittii bacteremia and those with A. nosocomialis bacteremia from 2000 to 2008 while matching for age, sex, Acute Physiology and Chronic Health Evaluation II score, and appropriate antimicrobial therapy. After adjustment, we accessed the clinical characteristics and 14- and 28-day mortalities. RESULTS: We found that the patients with A. pittii bacteremia had multiple comorbidities less often and received invasive procedures less frequently. The 14-day mortality rate of patients with A. pittii or A. nosocomialis bacteremia was 14% and 7%, respectively, whereas their 28-day mortality rate was 17% and 9%, respectively. Using the mortality rate in patients with A. nosocomialis bacteremia as a reference, the odds ratios for the 14- and 28-day crude morality in those with A. pittii were 2.16 [95% confidence interval (CI), 0.77-6.05] and 2.06 (95% CI, 0.82-5.15), respectively, whereas the adjusted odds ratios for 14- and 28-day mortality were 1.89 (95% CI, 0.56-6.14) and 1.67 (95% CI, 0.59-4.78) respectively. CONCLUSION: Our 8-year study showed that the mortality rate of A. pittii bacteremia was higher but the difference was not statistically significant.
Asunto(s)
Infecciones por Acinetobacter/microbiología , Infecciones por Acinetobacter/mortalidad , Acinetobacter/patogenicidad , Bacteriemia/microbiología , Bacteriemia/mortalidad , Acinetobacter/clasificación , Acinetobacter/aislamiento & purificación , Femenino , Hospitales de Enseñanza , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Análisis de Supervivencia , TaiwánRESUMEN
BACKGROUND/PURPOSE: Recurrent cellulitis is an important clinical issue but the optimal strategy for prophylaxis is not determined. Intramuscular benzathine penicillin at a 4-week interval had been adopted in our hospital and the study was conducted to evaluate the efficacy. METHODS: From January 1, 2009 to May 31, 2013, all patients aged ≥ 18 year, with a history of recurrent cellulitis and having received at least three shots of intramuscular benzathine penicillin for prophylaxis were retrospectively recruited for analysis. Two treatment periods (prophylaxis period and nonprophylaxis period) were defined. The effects of benzathine penicillin prophylaxis and patient characteristics on the incidence rate of recurrent cellulitis were analyzed using Poisson regression model. RESULTS: A total of 72 patients were enrolled, including 26 (36.1%) men. The most common underlying conditions were past surgery at the proximal side of the affected limb (38, 52.8%), malignancy (31, 43.1%), and diabetes mellitus (24, 33.3%). The incidence rate of recurrent cellulitis in the prophylaxis period was 0.73 episode/patient-year, significantly lower than that of 1.25 episodes/patient-year in the nonprophylaxis period (p < 0.001). Tinea pedis was a significant factor associated with increasing incidence of recurrent cellulitis in our cohort. CONCLUSION: Intramuscular benzathine penicillin at a 4-week interval may be an effective prophylactic strategy to reduce the incidence of cellulitis. Further studies are necessary to determine the factors associated with failure of prophylaxis as well as optimal individualized dosage and dosing interval of the prophylactic agent.
Asunto(s)
Profilaxis Antibiótica/métodos , Celulitis (Flemón)/tratamiento farmacológico , Celulitis (Flemón)/prevención & control , Penicilina G Benzatina/administración & dosificación , Penicilina G Benzatina/uso terapéutico , Anciano , Estudios de Cohortes , Femenino , Humanos , Inyecciones Intramusculares , Masculino , Persona de Mediana Edad , Factores de Riesgo , Infecciones Estreptocócicas/prevención & control , Resultado del TratamientoRESUMEN
BACKGROUND AND PURPOSE: Group B streptococcus (GBS) [Streptococcus agalactiae] is an emerging cause of disease in non-pregnant adults with underlying diseases. This retrospective study analyzed 90 episodes of GBS bacteremia in adults occurring over a 4-year period. METHODS: Basic and clinical data were collected by reviewing medical charts of patients. Blood cultures were performed on admission of patients suspected of bacteremia. Presence of underlying diseases, such as liver disease, heart disease, urinary tract disorders, and female-specific cancers, as well as possible portals of entry of infection was analyzed. RESULTS: In 56 episodes (62.2%), patients were aged 60 years or older and 40 (44.4%) episodes occurred in males. Skin and soft tissue were the most common sources of GBS bacteremia (22/90, 24.4%). GBS bacteremia was classified as primary in 50% of the episodes (45 patients). Liver diseases were more common in males, while malignancy was more common in females. Portals of entry with a significant gender predominance included skin and soft tissue in women (p=0.018), bone and joint in women (p=0.016), and urinary tract in men (p=0.042). The overall mortality rate was 18.9% and the attributable mortality rate was 7.8%. CONCLUSIONS: Elderly people and those with underlying diseases are particularly susceptible to GBS infections. Preventive strategies, including GBS vaccine and skin care, are likely to be particularly important in these high-risk groups.