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1.
FASEB J ; 34(7): 9156-9179, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32413239

RESUMO

Pseudomonas aeruginosa infection elicits the production of cytotoxic amyloids from lung endothelium, yet molecular mechanisms of host-pathogen interaction that underlie the amyloid production are not well understood. We examined the importance of type III secretion system (T3SS) effectors in the production of cytotoxic amyloids. P aeruginosa possessing a functional T3SS and effectors induced the production and release of cytotoxic amyloids from lung endothelium, including beta amyloid, and tau. T3SS effector intoxication was sufficient to generate cytotoxic amyloid release, yet intoxication with exoenzyme Y (ExoY) alone or together with exoenzymes S and T (ExoS/T/Y) generated the most virulent amyloids. Infection with lab and clinical strains engendered cytotoxic amyloids that were capable of being propagated in endothelial cell culture and passed to naïve cells, indicative of a prion strain. Conversely, T3SS-incompetent P aeruginosa infection produced non-cytotoxic amyloids with antimicrobial properties. These findings provide evidence that (1) endothelial intoxication with ExoY is sufficient to elicit self-propagating amyloid cytotoxins during infection, (2) pulmonary endothelium contributes to innate immunity by generating antimicrobial amyloids in response to bacterial infection, and (3) ExoY contributes to the virulence arsenal of P aeruginosa through the subversion of endothelial amyloid host-defense to promote a lung endothelial-derived cytotoxic proteinopathy.


Assuntos
Amiloide/química , Antibacterianos/farmacologia , Células Endoteliais/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Príons/farmacologia , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/isolamento & purificação , Animais , Proteínas de Bactérias/imunologia , Citotoxinas/farmacologia , Células Endoteliais/imunologia , Células Endoteliais/microbiologia , Feminino , Interações Hospedeiro-Patógeno , Humanos , Pulmão/imunologia , Pulmão/microbiologia , Masculino , Infecções por Pseudomonas/imunologia , Infecções por Pseudomonas/microbiologia , Ratos , Ratos Endogâmicos F344 , Ratos Sprague-Dawley , Virulência/efeitos dos fármacos
2.
FASEB J ; 33(9): 10300-10314, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31211919

RESUMO

Patients with nosocomial pneumonia exhibit elevated levels of neurotoxic amyloid and tau proteins in the cerebrospinal fluid (CSF). In vitro studies indicate that pulmonary endothelium infected with clinical isolates of either Pseudomonas aeruginosa, Klebsiella pneumoniae, or Staphylococcus aureus produces and releases cytotoxic amyloid and tau proteins. However, the effects of the pulmonary endothelium-derived amyloid and tau proteins on brain function have not been elucidated. Here, we show that P. aeruginosa infection elicits accumulation of detergent insoluble tau protein in the mouse brain and inhibits synaptic plasticity. Mice receiving endothelium-derived amyloid and tau proteins via intracerebroventricular injection exhibit a learning and memory deficit in object recognition, fear conditioning, and Morris water maze studies. We compared endothelial supernatants obtained after the endothelia were infected with P. aeruginosa possessing an intact [P. aeruginosa isolated from patient 103 (PA103) supernatant] or defective [mutant strain of P. aeruginosa lacking a functional type 3 secretion system needle tip complex (ΔPcrV) supernatant] type 3 secretion system. Whereas the PA103 supernatant impaired working memory, the ΔPcrV supernatant had no effect. Immunodepleting amyloid or tau proteins from the PA103 supernatant with the A11 or T22 antibodies, respectively, overtly rescued working memory. Recordings from hippocampal slices treated with endothelial supernatants or CSF from patients with or without nosocomial pneumonia indicated that endothelium-derived neurotoxins disrupted the postsynaptic synaptic response. Taken together, these results establish a plausible mechanism for the neurologic sequelae consequent to nosocomial bacterial pneumonia.-Balczon, R., Pittet, J.-F., Wagener, B. M., Moser, S. A., Voth, S., Vorhees, C. V., Williams, M. T., Bridges, J. P., Alvarez, D. F., Koloteva, A., Xu, Y., Zha, X.-M., Audia, J. P., Stevens, T., Lin, M. T. Infection-induced endothelial amyloids impair memory.


Assuntos
Amiloide/toxicidade , Endotélio Vascular/metabolismo , Pulmão/metabolismo , Transtornos da Memória/patologia , Infecções por Pseudomonas/complicações , Pseudomonas aeruginosa/isolamento & purificação , Proteínas tau/toxicidade , Amiloide/metabolismo , Animais , Endotélio Vascular/patologia , Medo , Feminino , Humanos , Aprendizagem , Pulmão/patologia , Masculino , Transtornos da Memória/etiologia , Transtornos da Memória/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Plasticidade Neuronal , Infecções por Pseudomonas/microbiologia , Proteínas tau/metabolismo
3.
J Antimicrob Chemother ; 73(6): 1677-1680, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29506044

RESUMO

Objectives: To identify the frequency of micafungin resistance among clinically significant isolates of Candida stored at our institution from 2005 to 2015. Chart review of patients with resistant isolates then informed the clinical setting and outcomes associated with these infections. Methods: Clinical Candida isolates had been stored at -80°C in Brucella broth with 20% glycerol from 2005. Isolates were tested using broth microdilution to determine micafungin MICs. All Candida glabrata isolates and all isolates demonstrating decreased susceptibility to micafungin were screened for FKS mutations using a Luminex assay. Results: In total, 3876 Candida isolates were tested for micafungin resistance, including 832 C. glabrata isolates. Of those, 33 isolates from 31 patients were found to have either decreased susceptibility to micafungin and/or an FKS mutation. C. glabrata accounted for the majority of these isolates. While bloodstream infections were found to have a very high mortality rate, isolates from other sites were uncommonly associated with 30-day mortality. Overall resistance rates were very low. Conclusions: Echinocandin resistance in C. glabrata has been increasingly reported but rates at our institution remain very low. We hypothesize that a focus on antifungal stewardship may have led to these observations. Knowledge of local resistance patterns is key to appropriate empirical treatment strategies.


Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candida/genética , Candidemia/mortalidade , Farmacorresistência Fúngica/genética , Equinocandinas/farmacologia , Centros Médicos Acadêmicos , Adulto , Candida/isolamento & purificação , Candida glabrata/efeitos dos fármacos , Candidíase/sangue , Candidíase/microbiologia , Caspofungina/farmacologia , Feminino , Proteínas Fúngicas/genética , Humanos , Masculino , Micafungina/farmacologia , Testes de Sensibilidade Microbiana , Mutação
4.
FASEB J ; 31(7): 2785-2796, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28314768

RESUMO

Patients who recover from pneumonia subsequently have elevated rates of death after hospital discharge as a result of secondary organ damage, the causes of which are unknown. We used the bacterium Pseudomonas aeruginosa, a common cause of hospital-acquired pneumonia, as a model for investigating this phenomenon. We show that infection of pulmonary endothelial cells by P. aeruginosa induces production and release of a cytotoxic amyloid molecule with prion characteristics, including resistance to various nucleases and proteases. This cytotoxin was self-propagating, was neutralized by anti-amyloid Abs, and induced death of endothelial cells and neurons. Moreover, the cytotoxin induced edema in isolated lungs. Endothelial cells and isolated lungs were protected from cytotoxin-induced death by stimulation of signal transduction pathways that are linked to prion protein. Analysis of bronchoalveolar lavage fluid collected from human patients with P. aeruginosa pneumonia demonstrated cytotoxic activity, and lavage fluid contained amyloid molecules, including oligomeric τ and Aß. Demonstration of long-lived cytotoxic agents after Pseudomonas infection may establish a molecular link to the high rates of death as a result of end-organ damage in the months after recovery from pneumonia, and modulation of signal transduction pathways that have been linked to prion protein may provide a mechanism for intervention.-Balczon, R., Morrow, K. A., Zhou, C., Edmonds, B., Alexeyev, M., Pittet, J.-F., Wagener, B. M., Moser, S. A., Leavesley, S., Zha, X., Frank, D. W., Stevens, T. Pseudomonas aeruginosa infection liberates transmissible, cytotoxic prion amyloids.


Assuntos
Citotoxinas/metabolismo , Proteínas Priônicas/toxicidade , Infecções por Pseudomonas/metabolismo , Pseudomonas aeruginosa , Animais , Edema , Células Endoteliais/microbiologia , Humanos , Camundongos , Neurônios/microbiologia , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/patologia , Proteínas Priônicas/metabolismo , Infecções por Pseudomonas/patologia , Ratos
5.
Clin Oral Investig ; 22(8): 2847-2858, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29476335

RESUMO

OBJECTIVE: Clinical typing methods of the oral pathogen Streptococcus mutans with molecular analysis can be very specific, but expensive. Repetitive extragenic palindromic PCR (rep-PCR) is a relatively inexpensive pre-screening alternative for isolate selection for additional analyses. This study evaluated the prediction accuracy of using rep-PCR to identify S. mutans multilocus sequence typing (MLST) sequence types (ST) among children and their family members. Potential S. mutans strain sources were evaluated for evidence of transmission. MATERIAL AND METHODS: Ten dendrograms (rep-PCR), with 20 isolates each of the 10 most common S. mutans genotypes, were generated from different subjects. Using a cut-off of 98% similarity, 7-11 isolates of each genotype were selected for MLST analysis to determine ST match/no-match. RESULTS: Overall, rep-PCR was 75% effective at determining MLST ST match/no-match and 90% effective when applied to related individuals. Most genotypes were further differentiated by MLST. MLST ST diversity was greatest for one genotype (genotype 12, G12) and evidence of transmission among children and their family members was identified by rep-PCR and MLST. Younger children (6 months to 4 years old) shared ST with their mothers but 50% of older children (5-9 years old) had ST not identified in their mother. Six ST were shared between different families and probable source members were identified. CONCLUSION: This study confirms that rep-PCR offers an affordable option to predict diverse isolates for downstream applications. CLINICAL RELEVANCE: Using a combined rep-PCR and MLST approach, it is possible to track probable transmission and strain sources for S. mutans genotypes.


Assuntos
Tipagem de Sequências Multilocus , Reação em Cadeia da Polimerase/métodos , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/transmissão , Streptococcus mutans/isolamento & purificação , Alabama , Criança , Pré-Escolar , Feminino , Genótipo , Humanos , Lactente , Estudos Longitudinais , Masculino , Núcleo Familiar , População Rural , Streptococcus mutans/genética
6.
Eur J Oral Sci ; 123(6): 416-24, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26443288

RESUMO

Studies using multilocus sequence typing (MLST) have demonstrated that Streptococcus mutans isolates are genetically diverse. Our laboratory previously demonstrated clonality of S. mutans using MLST but could not discount the possibility of sampling bias. In this study, the clonality of randomly selected S. mutans plaque isolates from African-American children was examined using MLST. Serotype and the presence of collagen-binding proteins (CBPs) encoded by cnm/cbm were also assessed. One-hundred S. mutans isolates were randomly selected for MLST analysis. Sequence analysis was performed and phylogenetic trees were generated using start2 and mega. Thirty-four sequence types were identified, of which 27 were unique to this population. Seventy-five per cent of the isolates clustered into 16 clonal groups. The serotypes observed were c (n = 84), e (n = 3), and k (n = 11). The prevalence of S. mutans isolates of serotype k was notably high, at 17.5%. All isolates were cnm/cbm negative. The clonality of S. mutans demonstrated in this study illustrates the importance of localized population studies and are consistent with transmission. The prevalence of serotype k, a recently proposed systemic pathogen, observed in this study, is higher than reported in most populations and is the first report of S. mutans serotype k in a United States population.


Assuntos
Streptococcus mutans , Criança , Variação Genética , Humanos , Tipagem de Sequências Multilocus , Filogenia , Sorogrupo
7.
J Clin Microbiol ; 2014 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-24622108

RESUMO

Withdrawn.

9.
Eur J Oral Sci ; 121(3 Pt 1): 148-55, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23659236

RESUMO

This longitudinal cohort study evaluated the diversity, commonality, and stability of Streptococcus mutans genotypes associated with dental caries history. Sixty-seven 5- and 6-yr-old children, considered as being at high caries risk, had plaque collected from baseline through 36 months for S. mutans isolation and genotyping using repetitive extragenic palindromic-PCR (4,392 total isolates). Decayed, missing, or filled surfaces (dmfs (primary teeth)/DMFS (secondary teeth)) for each child were recorded at baseline. At baseline, 18 distinct genotypes were found among 911 S. mutans isolates from 67 children (diversity), and 13 genotypes were shared by at least two children (commonality). The number of genotypes per individual was positively associated with the proportion of decayed surfaces (p-ds) at baseline. Twenty-four of the 39 children who were available at follow-up visits maintained a predominant genotype for the follow-up periods (stability) and this was negatively associated with the p-ds. The observed diversity, commonality, and stability of S. mutans genotypes represent a pattern of dental caries epidemiology in this high-caries-risk community, which suggests that fewer decayed surfaces are significantly associated with lower diversity and higher stability of S. mutans genotypes.


Assuntos
Negro ou Afro-Americano/genética , Impressões Digitais de DNA/métodos , Cárie Dentária/microbiologia , Streptococcus mutans/genética , Alabama/epidemiologia , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Contagem de Colônia Microbiana , Índice CPO , DNA Bacteriano/análise , Cárie Dentária/epidemiologia , Placa Dentária/microbiologia , Seguimentos , Variação Genética , Genótipo , Humanos , Estudos Longitudinais , Análise de Sequência com Séries de Oligonucleotídeos , Prevalência , Saliva/microbiologia , Estatísticas não Paramétricas , Streptococcus mutans/isolamento & purificação
10.
J Clin Microbiol ; 49(9): 3325-8, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21795510

RESUMO

Genetic relationships within ureaplasma serovars were investigated by pulsed-field gel electrophoresis (PFGE). One hundred thirteen Ureaplasma parvum isolates and 78 Ureaplasma urealyticum isolates were different from their ATCC serovar type strains and different within the same serovars. The organisms were geographically widespread. No unique patterns were associated with invasive disease.


Assuntos
Eletroforese em Gel de Campo Pulsado/métodos , Tipagem Molecular/métodos , Infecções por Ureaplasma/microbiologia , Ureaplasma urealyticum/classificação , Ureaplasma urealyticum/isolamento & purificação , Adulto , Criança , Pré-Escolar , Análise por Conglomerados , Feminino , Genótipo , Humanos , Lactente , Masculino , Polimorfismo Genético , Gravidez , Ureaplasma urealyticum/genética
11.
Mycoses ; 54(5): e438-42, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21535451

RESUMO

Poor susceptibility of Cryptococcus neoformans to fluconazole (FLC) is a matter of concern among clinicians in Africa. The emergence of resistance to FLC was recently reported in Kenya, but it is not known whether it is widespread. Thus, there is need for more antifungal drug susceptibility studies in Kenya. The aim of this study was to measure the in vitro antifungal drug susceptibilities of incident C. neoformans isolates from acquired immunodeficiency syndrome patients in Kenya. Antifungal susceptibility testing was performed in 67 C. neoformans isolates by broth microdilution method as outlined in the Clinical and Laboratory Standards Institute document M27-A3 using FLC, amphotericin B (AMB), voriconazole (VOR), ravuconazole (RAV) and flucytosine (5-FC). Isolates were grown on l-canavanine glycine bromothymol blue medium for serotype identification. Six per cent of the isolates were identified as C. neoformans var. gattii serotype B or C and 94% as C. neoformans var. neoformans. All isolates tested were susceptible to AMB, VOR and RAV (100%), and high susceptibilities were seen to FLC (97%), and 5-FC (90%). Only 3% and 10% of the isolates' susceptibility to FLC and 5-FC, respectively, was dose-dependent or intermediate. These results demonstrate high susceptibilities of incident C. neoformans isolates to FLC and AMB, antifungals used for treatment of cryptococcal meningitis in Kenya.


Assuntos
Antifúngicos/farmacologia , Líquido Cefalorraquidiano/microbiologia , Criptococose/microbiologia , Cryptococcus neoformans/efeitos dos fármacos , Cryptococcus neoformans/isolamento & purificação , Adulto , Meios de Cultura/química , Feminino , Infecções por HIV/complicações , Humanos , Quênia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade
12.
Toxins (Basel) ; 12(6)2020 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-32512716

RESUMO

Pseudomonas aeruginosa is an opportunistic pathogen that causes pneumonia in immunocompromised and intensive care unit (ICU) patients. During host infection, P. aeruginosa upregulates the type III secretion system (T3SS), which is used to intoxicate host cells with exoenzyme (Exo) virulence factors. Of the four known Exo virulence factors (U, S, T and Y), ExoU has been shown in prior studies to associate with high mortality rates. Preclinical studies have shown that ExoY is an important edema factor in lung infection caused by P. aeruginosa, although its importance in clinical isolates of P. aeruginosa is unknown. We hypothesized that expression of ExoY would be highly prevalent in clinical isolates and would significantly contribute to patient morbidity secondary to P. aeruginosa pneumonia. A single-center, prospective observational study was conducted at the University of Alabama at Birmingham Hospital. Mechanically ventilated ICU patients with a bronchoalveolar lavage fluid culture positive for P. aeruginosa were included. Enrolled patients were followed from ICU admission to discharge and clinical P. aeruginosa isolates were genotyped for the presence of exoenzyme genes. Ninety-nine patients were enrolled in the study. ExoY was present in 93% of P. aeruginosa clinical isolates. Moreover, ExoY alone (ExoY+/ExoU-) was present in 75% of P. aeruginosa isolates, compared to 2% ExoU alone (ExoY-/ExoU+). We found that bacteria isolated from human samples expressed active ExoY and ExoU, and the presence of ExoY in clinical isolates was associated with end-organ dysfunction. This is the first study we are aware of that demonstrates that ExoY is important in clinical outcomes secondary to nosocomial pneumonia.


Assuntos
Proteínas de Bactérias/metabolismo , Toxinas Bacterianas/metabolismo , Infecção Hospitalar/microbiologia , Glucosiltransferases/metabolismo , Insuficiência de Múltiplos Órgãos/microbiologia , Pneumonia Bacteriana/microbiologia , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/enzimologia , Fatores de Virulência/metabolismo , Animais , Proteínas de Bactérias/genética , Toxinas Bacterianas/genética , Células Cultivadas , Estado Terminal , Infecção Hospitalar/diagnóstico , Infecção Hospitalar/mortalidade , Feminino , Glucosiltransferases/genética , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/diagnóstico , Insuficiência de Múltiplos Órgãos/mortalidade , Pneumonia Bacteriana/diagnóstico , Pneumonia Bacteriana/mortalidade , Estudos Prospectivos , Infecções por Pseudomonas/diagnóstico , Infecções por Pseudomonas/mortalidade , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/patogenicidade , Ratos , Respiração Artificial/efeitos adversos , Fatores de Risco , Virulência , Fatores de Virulência/genética
13.
J Clin Microbiol ; 47(10): 3271-5, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19692558

RESUMO

We analyzed antifungal susceptibilities of 274 clinical Aspergillus isolates from transplant recipients with proven or probable invasive aspergillosis collected as part of the Transplant-Associated Infection Surveillance Network (TRANSNET) and examined the relationship between MIC and mortality at 6 or 12 weeks. Antifungal susceptibility testing was performed by the Clinical and Laboratory Standards Institute (CLSI) M38-A2 broth dilution method for amphotericin B (AMB), itraconazole (ITR), voriconazole (VOR), posaconazole (POS), and ravuconazole (RAV). The isolate collection included 181 Aspergillus fumigatus, 28 Aspergillus niger, 27 Aspergillus flavus, 22 Aspergillus terreus, seven Aspergillus versicolor, five Aspergillus calidoustus, and two Aspergillus nidulans isolates and two isolates identified as Aspergillus spp. Triazole susceptibilities were < or = 4 microg/ml for most isolates (POS, 97.6%; ITR, 96.3%; VOR, 95.9%; RAV, 93.5%). The triazoles were not active against the five A. calidoustus isolates, for which MICs were > or = 4 microg/ml. AMB inhibited 93.3% of isolates at an MIC of < or = 1 microg/ml. The exception was A. terreus, for which 15 (68%) of 22 isolates had MICs of >1 microg/ml. One of 181 isolates of A. fumigatus showed resistance (MIC > or = 4 microg/ml) to two of three azoles tested. Although there appeared to be a correlation of higher VOR MICs with increased mortality at 6 weeks, the relationship was not statistically significant (R2 = 0.61; P = 0.065). Significant relationships of in vitro MIC to all-cause mortality at 6 and 12 weeks for VOR or AMB were not found.


Assuntos
Antifúngicos/farmacologia , Aspergilose/microbiologia , Aspergillus/efeitos dos fármacos , Transplante/efeitos adversos , Aspergilose/mortalidade , Aspergillus/isolamento & purificação , Farmacorresistência Fúngica , Humanos , Hospedeiro Imunocomprometido , Testes de Sensibilidade Microbiana
14.
J Clin Microbiol ; 47(10): 3138-41, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19675215

RESUMO

A large aggregate collection of clinical isolates of aspergilli (n = 218) from transplant patients with proven or probable invasive aspergillosis was available from the Transplant-Associated Infection Surveillance Network, a 6-year prospective surveillance study. To determine the Aspergillus species distribution in this collection, isolates were subjected to comparative sequence analyses by use of the internal transcribed spacer and beta-tubulin regions. Aspergillus fumigatus was the predominant species recovered, followed by A. flavus and A. niger. Several newly described species were identified, including A. lentulus and A. calidoustus; both species had high in vitro MICs to multiple antifungal drugs. Aspergillus tubingensis, a member of the A. niger species complex, is described from clinical specimens; all A. tubingensis isolates had low in vitro MICs to antifungal drugs.


Assuntos
Aspergilose/microbiologia , Aspergillus/classificação , Aspergillus/genética , Transplante/efeitos adversos , Antifúngicos/farmacologia , Aspergillus/isolamento & purificação , DNA Fúngico/química , DNA Fúngico/genética , DNA Espaçador Ribossômico/química , DNA Espaçador Ribossômico/genética , Humanos , Hospedeiro Imunocomprometido , Testes de Sensibilidade Microbiana , Análise de Sequência de DNA , Tubulina (Proteína)/genética
15.
Open Forum Infect Dis ; 6(6): ofz241, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31214629

RESUMO

OBJECTIVE: Increased intracranial pressure (ICP) is an important complication of cryptococcal meningitis (CM) and impacts morbidity and mortality. Factors associated with permanent ventriculoperitoneal (VP) shunt placement are poorly characterized. METHOD: We conducted a retrospective cohort study of patients with CM at the University of Alabama at Birmingham from 1996 through 2015. Characteristics of patients at time of CM diagnosis who did and did not receive a VP shunt were compared with use of the 2-group chi-square test or Fisher exact test for categorical variables and the 2-group t test for continuous variables. Stepwise logistic regression analysis was used to determine predictors of shunt placement. RESULTS: Of 422 patients with cryptococcosis, 257 (60.9%) had CM. Mean age was 47.7 years, 71.6% were male, and 44.4% were African American. The most common underlying conditions were HIV (42.4%), solid organ transplantation (29.6%), and corticosteroid use (34.2%). Forty-four (17.1%) received a VP shunt a median of 17 days (range, 1-320 days) post-diagnosis. By multivariable analysis, baseline opening pressure >30 cm H2O (OR, 9.4; 95% CI, 3.0, 28.8; P < .0001), being a normal host (OR, 6.3; 95% CI, 1.5, 26.1; P = .011) and hydrocephalus (OR, 4.9, 95% CI, 1.3, 17.9); P = .017) were associated with increased odds of shunting (Table 2). In contrast, age (OR, 0.96; 95% CI, 0.92, 0.99; P = .037) and male gender (OR, 0.18; 95% CI, 0.06, 0.55; P = .023) were associated with decreased odds of shunting. CONCLUSIONS: Identification of factors at time of CM diagnosis associated with need for permanent VP shunt placement may allow for earlier, more aggressive treatment and potentially improve outcomes associated with increased ICP from cryptococcal meningitis.

16.
Mol Oral Microbiol ; 34(2): 64-73, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30667593

RESUMO

Streptococcus mutans, a primary bacterium associated with dental caries, has four known clinical serotypes (c, e, fand k). Certain serotypes, the presence of multiple serotypes and strains with collagen-binding proteins (CBP, Cnm and Cbm) have been linked with systemic disease. Evaluation of S mutans serotype distribution and caries association is needed in the United States. The purpose of this study was to evaluate the prevalence of S mutans serotypes from two cohorts of African-American children in rural Alabama using three sample types (saliva, plaque and individual S mutans isolates) by PCR detection for association with caries. Detection of CBP was also performed by PCR. In total, 129 children were evaluated and overall prevalence of serotypes were: serotype c(98%), e(26%), f(7%) and k(52%). Serotype c was statistically associated with higher caries scores in older children (P < 0.001) and serotype k was statistically more likely in females (P = 0.004). Fourteen per cent of children had CBP. Thirteen S mutans isolates from five children tested positive for both CBP. This study is the first to report on the prevalence of S mutans serotypes in a US population using the PCR-based approach. The frequency of serotype k in this study is the highest reported in any population, illustrating the need for further study to determine the prevalence of this clinically relevant serotype in the US. This is the first study to report S mutans isolates with both Cnm and Cbm in the same strain, and further analysis is needed to determine the clinical significance of these strains.


Assuntos
Adesinas Bacterianas/classificação , Proteínas de Transporte/classificação , Cárie Dentária/microbiologia , Reação em Cadeia da Polimerase/métodos , Sorogrupo , Sorotipagem/métodos , Streptococcus mutans , Adesinas Bacterianas/genética , Negro ou Afro-Americano , Alabama , Proteínas de Transporte/genética , Criança , Pré-Escolar , Colágeno , DNA Bacteriano/isolamento & purificação , Placa Dentária , Feminino , Genes Bacterianos , Variação Genética , Humanos , Masculino , População Rural , Saliva , Streptococcus mutans/genética , Streptococcus mutans/isolamento & purificação
17.
Antimicrob Agents Chemother ; 52(9): 3022-8, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18591269

RESUMO

Recent studies of nonneutropenic patients with candidemia or candidiasis suggest that fluconazole pharmacodynamic parameters correlate with clinical outcomes; however, additional data of correlation to mortality in patients with candidemia would be valuable. We assessed the impact of MICs for Candida, fluconazole pharmacodynamics, and patient characteristics on all-cause mortality with use of a prospective cohort of 96 hospitalized patients with candidemia. Among 84 patients for whom Candida isolates were available for testing, the most frequent Candida species isolated were Candida albicans (44%), followed by Candida parapsilosis (20.2%), and Candida glabrata (20.2%). Fluconazole resistance (MIC of >or=64 microg/ml) was present in 7 (8.3%) to 10 (11.9%) of 84 isolates, depending on the MIC endpoint determination method (50% or 80% inhibition read at 24 or 48 h). Overall mortality occurred in 27 (28.1%) of 96 patients, and nonsurvivors were more likely to have fluconazole-resistant isolates (25% versus 6.7%; P = 0.02). Multivariable analysis demonstrated an association between fluconazole resistance and mortality, but it did not reach statistical significance (odds ratio, 5.3; 95% confidence interval, 0.8 to 33.4; P = 0.08). By pharmacodynamic analysis, a fluconazole area under the concentration-time curve/MIC of <11.5 or MIC of >or=64 was associated with increased patient mortality (P

Assuntos
Antifúngicos , Candida/efeitos dos fármacos , Candidíase/mortalidade , Farmacorresistência Fúngica , Fluconazol , Fungemia/mortalidade , APACHE , Adulto , Idoso , Antifúngicos/administração & dosagem , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida/classificação , Candidíase/microbiologia , Relação Dose-Resposta a Droga , Feminino , Fluconazol/administração & dosagem , Fluconazol/farmacologia , Fluconazol/uso terapêutico , Fungemia/microbiologia , Humanos , Modelos Logísticos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Análise de Sobrevida
19.
South Med J ; 101(1): 40-5, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18176290

RESUMO

BACKGROUND: The epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) was investigated at a tertiary care hospital, and relationship was made between the clinical and genetic definitions of community- and healthcare-associated MRSA. METHODS: Nonduplicate isolates of S. aureus were collected during 2004. Isolates were classified clinically as community-associated (CA) or healthcare-associated (HA). Molecular typing studies were performed on the isolates. RESULTS: Four hundred and two S. aureus isolates were collected, of which 281 (70%) were MRSA. By clinical definition, 58 (21%) were classified as CA-MRSA and 215 (77%) as HA-MRSA. Among CA-MRSA, 36 (62%) harbored a SCCmec type IV gene. None of the SCCmec type IV CA-MRSA expressed inducible clindamycin resistance (MLSBi). Among 57 HA-MRSA isolates, 31 (54.4%) harbored a SCCmec type IV gene; MLSBi present in 5 (16%). Type IV SCCmec MRSA were most often associated with skin and soft tissue infections (RR 3.34 95% CI 1.43, 7.8). USA300 was the most common genotype among both CA- and HA-MRSA. CONCLUSIONS: Community-associated MRSA is a prominent pathogen with its most common genotype, USA300, representing a significant proportion of CA- and HA-MRSA infections in our institution. Clinical definitions of CA- and HA- status do not correlate well with the genetic definitions, particularly for HA-MRSA.


Assuntos
Infecção Hospitalar/epidemiologia , Infecções Estafilocócicas/epidemiologia , Alabama/epidemiologia , Infecções Comunitárias Adquiridas/epidemiologia , Eletroforese em Gel de Campo Pulsado , Genótipo , Hospitais Universitários , Resistência a Meticilina , Estudos Retrospectivos , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/classificação , Staphylococcus aureus/genética
20.
Infect Control Hosp Epidemiol ; 39(12): 1419-1424, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30296959

RESUMO

OBJECTIVE: Due to concerns over increasing fluoroquinolone (FQ) resistance among gram-negative organisms, our stewardship program implemented a preauthorization use policy. The goal of this study was to assess the relationship between hospital FQ use and antibiotic resistance. DESIGN: Retrospective cohort. SETTING: Large academic medical center. METHODS: We performed a retrospective analysis of FQ susceptibility of hospital isolates for 5 common gram-negative bacteria: Acinetobacter spp., Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Primary endpoint was the change of FQ susceptibility. A Poisson regression model was used to calculate the rate of change between the preintervention period (1998-2005) and the postimplementation period (2006-2016). RESULTS: Large rates of decline of FQ susceptibility began in 1998, particularly among P. aeruginosa, Acinetobacter spp., and E. cloacae. Our FQ restriction policy improved FQ use from 173 days of therapy (DOT) per 1,000 patient days to <60 DOT per 1,000 patient days. Fluoroquinolone susceptibility increased for Acinetobacter spp. (rate ratio [RR], 1.038; 95% confidence interval [CI], 1.005-1.072), E. cloacae (RR, 1.028; 95% CI, 1.013-1.044), and P. aeruginosa (RR, 1.013; 95% CI, 1.006-1.020). No significant change in susceptibility was detected for K. pneumoniae (RR, 1.002; 95% CI, 0.996-1.008), and the susceptibility for E. coli continued to decline, although the decline was not as steep (RR, 0.981; 95% CI, 0.975-0.987). CONCLUSIONS: A stewardship-driven FQ restriction program stopped overall declining FQ susceptibility rates for all species except E. coli. For 3 species (ie, Acinetobacter spp, E. cloacae, and P. aeruginosa), susceptibility rates improved after implementation, and this improvement has been sustained over a 10-year period.


Assuntos
Antibacterianos/farmacologia , Gestão de Antimicrobianos/organização & administração , Farmacorresistência Bacteriana , Fluoroquinolonas/farmacologia , Acinetobacter/efeitos dos fármacos , Acinetobacter/isolamento & purificação , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/microbiologia , Alabama , Enterobacter cloacae/efeitos dos fármacos , Enterobacter cloacae/isolamento & purificação , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/microbiologia , Humanos , Testes de Sensibilidade Microbiana , Autorização Prévia/organização & administração , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/isolamento & purificação , Estudos Retrospectivos , Centros de Atenção Terciária
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