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1.
Adv Exp Med Biol ; 1145: 181-195, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31364079

RESUMO

Biofilm is an adaptive bacterial strategy whereby microorganisms become encased in a complex glycoproteic matrix. The low concentration of oxygen and nutrients in this environment leads to heterogeneous phenotypic changes in the bacteria, with antimicrobial tolerance being of paramount importance. As with other antibiotics, the activity of colistin is impaired by biofilm-embedded bacteria. Therefore, the recommendation for administering high doses in combination with a second drug, indicated for planktonic infections, remains valid in this setting. Notably, colistin has activity against metabolically inactive biofilm-embedded cells located in the inner layers of the biofilm structure. This is opposite and complementary to the activity of other antimicrobials that are able to kill metabolically active cells in the outer layers of the biofilm. Several experimental models have shown a higher activity of colistin when used in combination with other agents, and have reported that this can avoid the emergence of colistin-resistant subpopulations. Most experience of colistin in biofilm-associated infections comes from patients with cystic fibrosis, where the use of nebulized colistin allows high concentrations to reach the site of the infection. However, limited clinical experience is available in other scenarios, such as osteoarticular infections or device-related central nervous system infections caused by multi-drug resistant microorganisms. In the latter scenario, the use of intraventricular or intrathecal colistin also permits high local concentrations and good clinical results. Overall, the efficacy of intravenous colistin seems to be poor, but its association with a second antimicrobial significantly increases the response rate. Given its activity against inner bioflm-embedded cells, its possible role in combination with other antibiotics, beyond last-line therapy situations, should be further explored.


Assuntos
Antibacterianos/uso terapêutico , Biofilmes/efeitos dos fármacos , Colistina/uso terapêutico , Doenças Ósseas Infecciosas/tratamento farmacológico , Infecções do Sistema Nervoso Central/tratamento farmacológico , Fibrose Cística/microbiologia , Farmacorresistência Bacteriana Múltipla , Humanos , Testes de Sensibilidade Microbiana
2.
Curr Med Sci ; 39(3): 449-454, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31209818

RESUMO

Central nervous system (CNS) infections are associated with high mortality rates. The clinical presentation of many CNS infections by different pathogens is difficult to distinguish, but the definite diagnosis of the etiology is critical for effective therapy and prognosis. The aim of this study was to explore the etiology of CNS infections with definite diagnoses based on data from a clinical microbiology laboratory in Tongji Hospital, a teaching hospital in China, obtained over a six-year period. We conducted a retrospective study on all cerebrospinal fluid (CSF) specimens submitted to our clinical microbiology laboratory from September, 2012 to December, 2018. The etiology of CNS infections caused by Cryptococcus neoformans, Mycobacterium tuberculosis and common bacteria was analyzed. Antimicrobial susceptibility testing was conducted on all isolates. The results showed that 1972 cases of CNS infections were identified from 18 300 CSF specimens. Common bacterial meningitis (BM), cryptococcal meningitis (CM) and tuberculous meningitis (TM) accounted for 86.3% (677/785), 9.4% (74/785) and 4.3% (34/785) respectively of cases over the six-year period. BM was the most common among the different age groups, followed by CM. Of the TM cases, 44.1% (15/34) were distributed within the age group of 15-34 years, whereas for CM cases, 52.7% (39/74) occurred within the 35-54-year age group, and the age distribution of BM cases was fairly even. Among the bacterial pathogens isolated, Staphylococcus epidermidis was the most common, accounting for 12.5% (98/785), followed by Acinetobacter baumannii (ABA) and Staphylococcus aureus (SAU), accounting for 11.8% (93/785) and 7.6% (60/785) respectively. The resistance rates to antibiotics were >75%, with the exception of the resistance rate of ABA to tegafycline, which was <3%. More than 60% of SAU strains displayed resistance to penicillin, oxacillin, ampicillin/sulbactam, cefazolin, cefuroxime, gentamycin, tobramycin, erythromycin and levofloxacin, whereas more than 90% of SAU strains showed susceptibility to trimethoprim/sulfamethoxazole, tegafycline, vancomycin, teicoplanin and linezolid. For C. neoformans, the susceptibility rates to amphotericin B, 5-fluorocytosine, fluconazol and voriconazole were >95%. Analysis of samples from patients with CNS infection in a clinical microbiology laboratory at a teaching hospital in China over a six-year period indicated that the most common etiological agents were the bacteria ABA and SAU. The antibiotic resistance levels of ABA were found to be high and of concern, whereas isolates of C. neoformans were found to be sensitive to antifungal antibiotics.


Assuntos
Acinetobacter baumannii/isolamento & purificação , Infecções Bacterianas/diagnóstico , Infecções do Sistema Nervoso Central/diagnóstico , Cryptococcus neoformans/isolamento & purificação , Mycobacterium tuberculosis/isolamento & purificação , Staphylococcus aureus/isolamento & purificação , Staphylococcus epidermidis/isolamento & purificação , Acinetobacter baumannii/classificação , Acinetobacter baumannii/efeitos dos fármacos , Adolescente , Adulto , Idoso , Antibacterianos/classificação , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/microbiologia , Sistema Nervoso Central/microbiologia , Sistema Nervoso Central/patologia , Infecções do Sistema Nervoso Central/tratamento farmacológico , Infecções do Sistema Nervoso Central/epidemiologia , Infecções do Sistema Nervoso Central/microbiologia , Criança , China/epidemiologia , Cryptococcus neoformans/classificação , Cryptococcus neoformans/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla , Feminino , Hospitais de Ensino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mycobacterium tuberculosis/classificação , Mycobacterium tuberculosis/efeitos dos fármacos , Prevalência , Estudos Retrospectivos , Staphylococcus aureus/classificação , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus epidermidis/classificação , Staphylococcus epidermidis/efeitos dos fármacos
3.
Surg Infect (Larchmt) ; 20(6): 460-464, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30942663

RESUMO

Background: Post-operative central nervous system infection (PCNSI) caused by multi-drug-resistant/extensively drug-resistant (MDR/XDR) Acinetobacter baumannii is a severe complication. This study aimed to analyze the clinical presentation and treatment of this disorder. Patients and Methods: A retrospective study that recruited patients having PCNSI caused by MDR/XDR Acinetobacter baumannii was performed at our institute. The patients' demographic information and clinical data were recorded and analyzed. To analyze treatment, we assigned patients to different groups according to whether they had intraventricular/intrathecal injection of antibiotic agents or cerebrospinal fluid (CSF) drainage therapy. Results: Twenty-four patients were included. The risk factors were classified into two categories: environmental factors (intensive care unit stay, tracheal intubation or tracheotomy, positive culture of MDR/XDR Acinetobacter baumannii from other samples) or infectious approaches (CSF drainage, incision CSF leakage). Cerebrospinal fluid sterilization was achieved in 13 patients (54.2%) and the 30-day mortality was 50%. In the seven patients having intraventricular/intrathecal injection of antibiotic agents, the CSF sterilization rate was 71.4% (5/7) and 30-day mortality was 28.6% (2/7), compared with 47.1% (8/17; p = 0.27) and 58.8% (10/17; p = 0.18) in patients having only intravenous antibiotic agents. In 19 patients having CSF drainage therapy for PCNSI, the CSF sterilization rate was 63.2% (12/19) and 30-day mortality was 42.1% (8/19) compared with 20% (1/5; p = 0.08) and 80% (4/5; p = 0.13) in the remaining patients. Conclusions: The risk factors for PCNSI caused by Acinetobacter baumannii can be classified in two categories: environmental factors or infectious approaches. Both intraventricular/intrathecal injection of antibiotic agents and CSF drainage are helpful for CSF sterilization.


Assuntos
Infecções por Acinetobacter/patologia , Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/uso terapêutico , Infecções do Sistema Nervoso Central/patologia , Farmacorresistência Bacteriana Múltipla , Procedimentos Neurocirúrgicos/efeitos adversos , Infecção da Ferida Cirúrgica/patologia , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções do Sistema Nervoso Central/tratamento farmacológico , Infecções do Sistema Nervoso Central/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Infecção da Ferida Cirúrgica/tratamento farmacológico , Infecção da Ferida Cirúrgica/mortalidade , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
4.
BMJ Case Rep ; 12(4)2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30992281

RESUMO

We present the case of a 14-year-old immune-competent girl with ventriculoperitoneal shunt who was repeatedly hospitalised with meningeal signs despite repeated shunt revision surgeries. Eventually Mycobacterium fortuitum was isolated and the patient improved after specific treatment. M. fortuitum is a rapidly growing, non-tuberculous mycobacterium (NTM). NTMs are associated with postsurgical, post-trauma and device-related infections. Most of the present-day surgical equipment, catheters, prostheses and indwelling devices comprised silicone, stainless steel, polyvinyl chloride and polycarbonate, on which NTMs have the tendency to form biofilms. Central nervous system infection caused by NTM carries a high mortality rate (ranging from 35% to 70%), especially in immune-compromised patients. Indwelling device removal along with prolonged treatment with a combination regimen is recommended in such cases.


Assuntos
Infecções do Sistema Nervoso Central/diagnóstico , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Derivação Ventriculoperitoneal/efeitos adversos , Adolescente , Antibacterianos/administração & dosagem , Infecções do Sistema Nervoso Central/líquido cefalorraquidiano , Infecções do Sistema Nervoso Central/tratamento farmacológico , Feminino , Humanos , Imunocompetência , Infecções por Mycobacterium não Tuberculosas/líquido cefalorraquidiano , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Mycobacterium fortuitum/isolamento & purificação , Reoperação/efeitos adversos
5.
Emerg Infect Dis ; 25(5): 898-910, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31002063

RESUMO

During 2003-2011, we recruited 1,065 patients of all ages admitted to Mahosot Hospital (Vientiane, Laos) with suspected central nervous system (CNS) infection. Etiologies were laboratory confirmed for 42.3% of patients, who mostly had infections with emerging pathogens: viruses in 16.2% (mainly Japanese encephalitis virus [8.8%]); bacteria in 16.4% (including Orientia tsutsugamushi [2.9%], Leptospira spp. [2.3%], and Rickettsia spp. [2.3%]); and Cryptococcus spp. fungi in 6.6%. We observed no significant differences in distribution of clinical encephalitis and meningitis by bacterial or viral etiology. However, patients with bacterial CNS infection were more likely to have a history of diabetes than others. Death (26.3%) was associated with low Glasgow Coma Scale score, and the mortality rate was higher for patients with bacterial than viral infections. No clinical or laboratory variables could guide antibiotic selection. We conclude that high-dependency units and first-line treatment with ceftriaxone and doxycycline for suspected CNS infections could improve patient survival in Laos.


Assuntos
Infecções do Sistema Nervoso Central/etiologia , Adolescente , Adulto , Infecções do Sistema Nervoso Central/diagnóstico , Infecções do Sistema Nervoso Central/tratamento farmacológico , Criança , Pré-Escolar , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/etiologia , Feminino , Política de Saúde , Humanos , Lactente , Encefalite Infecciosa/etiologia , Encefalite Infecciosa/microbiologia , Encefalite Infecciosa/virologia , Laos , Masculino , Meningite/etiologia , Meningite/microbiologia , Meningite/virologia , Estudos Prospectivos , Adulto Jovem
6.
Medicine (Baltimore) ; 98(15): e15139, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30985683

RESUMO

RATIONALE: The treatment of intracranial Acinetobacter baumannii infections is made difficult by multidrug-resistance poor drug penetration through the blood-brain barrier (BBB). Although tigecycline appears to be effective against A baumannii, it is only administered intravenously because it does not readily cross the BBB. The addition of intraventricular (IVT) or intrathecal infusions of tigecycline could revolutionize clinical therapy for intracranial A baumannii infections. However, there are few reports on the successful use of such treatments. PATIENT CONCERNS: We report the case of a 17-year-old male who presented with high fever and neck rigidity after intracranial drainage. DIAGNOSIS: Intracranial infection with extensively drug-resistant A baumannii after intracranial drainage. INTERVENTIONS: On the advice of a clinical pharmacist, the patient was administered intrathecal infusions of tigecycline after treatment failure with IVT tigecycline. OUTCOMES: The patient's body temperature returned to normal. Thereafter, the patient was in good clinical condition without signs of cerebrospinal fluid infection and tuberculosis. LESSONS: However, when central nervous system infections fail IVT tigecycline, clinicians should consider changing to intrathecal tigecycline infusions rather than raising the dose of IVT tigecycline. In addition, the co-administration of tigecycline with other drugs that can penetrate the BBB should not be ruled out.


Assuntos
Infecções por Acinetobacter/tratamento farmacológico , Acinetobacter baumannii , Antibacterianos/administração & dosagem , Encefalopatias/tratamento farmacológico , Infecções do Sistema Nervoso Central/tratamento farmacológico , Tigeciclina/administração & dosagem , Infecções por Acinetobacter/diagnóstico por imagem , Adolescente , Encefalopatias/diagnóstico por imagem , Infecções do Sistema Nervoso Central/diagnóstico por imagem , Farmacorresistência Bacteriana Múltipla , Humanos , Infusões Intraventriculares , Infusão Espinal , Masculino
7.
Surg Infect (Larchmt) ; 20(4): 292-297, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30785859

RESUMO

Background: Intra-cranial infection with Acinetobacter baumannii is a tough problem because of the presence of multi-resistance and poor drug penetration through the blood-brain barrier. Such intra-cranial infections can lead to serious complications and death. We retrospectively analyzed the culture results and clinical characteristics of patients with intra-cranial infections in our hospital and suggested intravenous (IV) meropenem and intra-thecal (IT) amikacin therapy may be effective in the management of A. baumannii infection. Case presentation: We reported four cases of post-neuro-surgical A. baumannii intra-cranial infection whose clinical futures were high fever and consciousness disturbance. Our patients were treated successfully with IV meropenem and IT amikacin. Conclusion: We presented our cases of pandrug-resistant A. baumannii intra-cranial infection that was managed successfully with a systemic provision of IV meropenem and IT amikacin. Therefore, these cases exemplify that systemic administration of IV meropenem and IT amikacin can be a good therapeutic option against A. baumannii intra-cranial infection when colistin is not available.


Assuntos
Infecções por Acinetobacter/tratamento farmacológico , Amicacina/administração & dosagem , Antibacterianos/administração & dosagem , Infecções do Sistema Nervoso Central/tratamento farmacológico , Meropeném/administração & dosagem , Procedimentos Neurocirúrgicos/efeitos adversos , Infecção da Ferida Cirúrgica/tratamento farmacológico , Infecções por Acinetobacter/patologia , Acinetobacter baumannii/isolamento & purificação , Administração Intravenosa , Adulto , Idoso , Infecções do Sistema Nervoso Central/patologia , Feminino , Humanos , Injeções Espinhais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/patologia , Resultado do Tratamento
8.
World Neurosurg ; 126: e1-e7, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30550873

RESUMO

OBJECTIVE: To evaluate values of cerebrospinal fluid (CSF) and serum procalcitonin (PCT) for diagnosis of intracranial infection after craniotomy and relationship between them and to explore value of PCT in guiding clinical use of antibiotics. METHODS: The incidence of intracranial infection in 21 patients undergoing craniotomy was reviewed. CSF samples and venous blood were collected for analysis. Diagnostic parameters were calculated via receiver operating characteristic curves, and inflammatory indicators were analyzed before and after administration of antibiotics in the infection group. As a control group, 32 patients without infection were recruited for the same measurements. RESULTS: CSF and serum PCT levels in the infection group were higher than levels in the noninfection group (P < 0.05), and diagnostic efficiency of CSF PCT (area under the curve = 0.86, diagnostic odds ratio = 41.40) was superior to serum PCT (area under the curve = 0.66, diagnostic odds ratio = 3.40). Diagnostic efficiency was more powerful when serial testing was used (specificity = 0.99, positive likelihood ratio = 37.10, diagnostic odds ratio = 54.45). All inflammatory indicators decreased after administration of antibiotics except CSF protein (P = 0.129), and no obvious correlation was seen between CSF and serum PCT. Dynamic change of PCT can be used as a reference for adjusting antibiotics. CSF PCT can also be used as an indicator to identify intracranial infection with gram-negative bacteria. CONCLUSIONS: CSF PCT is a good marker for intracranial infection and could be used to help confirm intracranial infection and provide guidance for clinical use of antibiotics when combined with serum PCT.


Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Infecções do Sistema Nervoso Central/diagnóstico , Infecções do Sistema Nervoso Central/tratamento farmacológico , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/tratamento farmacológico , Pró-Calcitonina/sangue , Pró-Calcitonina/líquido cefalorraquidiano , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções do Sistema Nervoso Central/microbiologia , Craniotomia , Feminino , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Inflamação/sangue , Inflamação/líquido cefalorraquidiano , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Valores de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
9.
PLoS One ; 13(10): e0205316, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30300411

RESUMO

Acute central nervous system (CNS) infections in children in sub-Saharan Africa are often fatal. Potential contributors include late presentation, limited diagnostic capacity and inadequate treatment. A more nuanced understanding of treatment practices with a goal of optimizing such practices is critical to prevent avoidable case fatality. We describe empiric antimicrobial treatment, antibiotic resistance and treatment adequacy in a prospective cohort of 459 children aged two months to 12 years hospitalised for suspected acute CNS infections in Mbarara, Uganda, from 2009 to 2012. Among these 459 children, 155 had a laboratory-confirmed diagnosis of malaria (case-fatality rate [CFR] 14%), 58 had bacterial infections (CFR 24%) and 6 children had mixed malaria and bacterial infections (CFR 17%). Overall case fatality was 18.1% (n = 83). Of 219 children with laboratory-confirmed malaria and/or bacterial infections, 182 (83.1%) received an adequate antimalarial and/or antibiotic on the day of admission and 211 (96.3%) within 48 hours of admission. The proportion of those receiving adequate treatment was similar among survivors and non-survivors. All bacterial isolates were sensitive to ceftriaxone except one Escherichia coli isolate with extended-spectrum beta-lactamase (ESBL). The observed high mortality was not a result of inadequate initial antimicrobial treatment at the hospital. The epidemiology of CNS infection in this setting justifies empirical use of a third-generation cephalosporin, however antibiotic resistance should be monitored closely.


Assuntos
Infecções do Sistema Nervoso Central/epidemiologia , Coinfecção/epidemiologia , Infecções por Escherichia coli/epidemiologia , Malária/epidemiologia , Antibacterianos/uso terapêutico , Anti-Infecciosos/uso terapêutico , Ceftriaxona/uso terapêutico , Infecções do Sistema Nervoso Central/tratamento farmacológico , Criança , Pré-Escolar , Coinfecção/tratamento farmacológico , Coinfecção/microbiologia , Farmacorresistência Bacteriana/genética , Escherichia coli/efeitos dos fármacos , Escherichia coli/patogenicidade , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Feminino , Humanos , Lactente , Malária/tratamento farmacológico , Malária/microbiologia , Masculino , Uganda/epidemiologia , beta-Lactamases/genética
10.
Rev Esp Quimioter ; 31 Suppl 1: 56-61, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30209926

RESUMO

Diagnosis of CNS infections remains a great challenge in immunocompromised patients with solid cancer or hematological disorders, as it happens with transplant recipients, since symptoms might both be masked and be mimicked by other conditions such as metabolic disturbances or consequences of antineoplastic treatment and the administration of immunosuppressive drugs. Thus, awareness of this complication is crucial and any suspicion of a CNS infection should lead to make an early diagnosis and to choose an appropriate empirical treatment to improve the outcome in this population.


Assuntos
Infecções do Sistema Nervoso Central/microbiologia , Hospedeiro Imunocomprometido , Infecções do Sistema Nervoso Central/diagnóstico , Infecções do Sistema Nervoso Central/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas , Humanos
11.
Jpn J Infect Dis ; 71(5): 338-342, 2018 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-29848841

RESUMO

While we previously detected anti-bornavirus antibodies via radioligand assay in psychiatric patients, we did not examine the viral pathogenicity in these individuals. Herein, we present 2 psychiatric patients who were seropositive for bornavirus and whose treatment-resistant symptoms improved after oral administration of ribavirin, a broad-spectrum antiviral agent. Cerebrospinal fluid analysis indicated that ribavirin affected the central nervous system of these patients. Ribavirin ameliorated intermittent involuntary head shaking, which is reminiscent of a symptom observed in bornavirus-infected animals. Using radioligand assays to examine the serial sera of these patients, we found a relationship between the titers of anti-bornavirus antibodies and the change in the patients' symptoms. Our findings suggest there is a relationship between bornavirus infection and human symptoms and that ribavirin may be useful in suppressing chronic bornavirus infection in some neuropsychiatric patients. However, the possibility remains that some other known or unknown virus other than bornavirus that is sensitive to ribavirin may have caused the symptoms. Additional evidence that directly indicates the causative relationship between bornavirus infection and human symptoms is needed before establishing the pathogenesis and treatment for human bornavirus infection.


Assuntos
Antivirais/administração & dosagem , Bornaviridae/isolamento & purificação , Infecções do Sistema Nervoso Central/diagnóstico , Infecções do Sistema Nervoso Central/tratamento farmacológico , Infecções por Mononegavirales/diagnóstico , Infecções por Mononegavirales/tratamento farmacológico , Ribavirina/administração & dosagem , Administração Oral , Adulto , Anticorpos Antivirais/sangue , Infecções do Sistema Nervoso Central/patologia , Feminino , Humanos , Masculino , Infecções por Mononegavirales/patologia , Resultado do Tratamento
12.
Clin Neurol Neurosurg ; 170: 140-158, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29800828

RESUMO

Central nervous system infections can be complications of neurosurgical procedures or can occur spontaneously, and occasionally lead to devastating neurological complications, increased rate of mortality, and lengthier stays in the hospital, subsequently increasing costs. The use of intrathecal antibiotics to bypass the blood brain barrier and provide effective concentrations to the central nervous system has been described as an adjunct treatment option. However, the regimens of antibiotics utilized intrathecally have not been standardized. Our review of the literature included all articles from MEDLINE/PubMed and Ovid from inception to 2017 and after removing duplicates and checking for relevancy, the final number of articles yielded was 200. This review summarizes the use of antibiotics intrathecally to treat CNS infections, the dosages, therapeutic efficacies, and highlights significant side effects. The current rates of mortality in patients suffering from CNS infections is high, thus intrathecal antibiotic therapy should be considered as a potential therapeutic strategy in this patient population. Multiple antibiotics have demonstrated safety and efficacy when used intrathecally, and further studies, including clinical trials, need to be performed to elucidate their full therapeutic potential and outline proper dosing regimens.


Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/líquido cefalorraquidiano , Infecções do Sistema Nervoso Central/líquido cefalorraquidiano , Infecções do Sistema Nervoso Central/tratamento farmacológico , Infecções do Sistema Nervoso Central/mortalidade , Ventriculite Cerebral/líquido cefalorraquidiano , Ventriculite Cerebral/tratamento farmacológico , Ventriculite Cerebral/mortalidade , Humanos , Injeções Espinhais , Mortalidade/tendências , Resultado do Tratamento
13.
BMC Infect Dis ; 18(1): 231, 2018 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-29783937

RESUMO

BACKGROUND: As an opportunistic pathogen, E. gallinarum mainly leads to nosocomial infections, and it's multi-drug resistance has gained more and more attention. Central nervous system infections caused by E. gallinarum are rare, but have been reported more often in recent years. The previous cases were generally secondary to neurosurgery, especially ventriculoperitoneal shunts. In recent years, the cases largely occurred in patients with impaired immune function. The patient in our report may have had dual risk factors (immune impairment and an invasive surgical procedure). CASE PRESENTATION: The patient, a 35-year-old female, was admitted to our hospital for headaches of 3 days duration accompanied by nausea and vomiting for 2 days. The patient had fevers and chills for 3 days before admission; the peak body temperature was 38.5 °C. The patient had a splenectomy in our hospital 2 years earlier for thrombocytopenia and was thought to be immunocompromised. The abnormal findings on physical examination and laboratory testing were as follows: neck stiffness, present; lumbar puncture: pressure, 300 mmH2O; Pandy's test, positive; white blood cell (WBC) count, 1536 × 106/L; monocyte count, 602 × 106/L; monocyte percentage, 39.2%; multinucleate cell count, 934 × 106/L; multinucleate cell percentage, 60.8%; protein, 1.08 g/L; WBC count, 21.1 × 109/ L; neutrophil percentage, 85.3%; neutrophil count, 20.55 × 109/L; C reactive protein (CRP): 136.4 mg/L; procalcitonin, 6.70 ng/mL. The patient was given meropenem (2.0 g, intravenous infusion, every 8 h) for anti-infection supplemented with other symptomatic support treatments. The patient's fever and headache had no significant relief. CONCLUSIONS: Central nervous system infections caused by E. gallinarum are rare, but should be suspected, particularly inpatients with impaired immune function or ineffective treatment. Avoiding long-term invasive treatment and improving immunity are helpful to reduce the occurrence of E. gallinarum infections. Early detection and diagnosis, as well as rational antibiotic use, are the keys to achieve satisfactory efficacy.


Assuntos
Infecções do Sistema Nervoso Central/diagnóstico , Meningite/diagnóstico , Adulto , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções do Sistema Nervoso Central/tratamento farmacológico , Infecções do Sistema Nervoso Central/microbiologia , Enterococcus/efeitos dos fármacos , Enterococcus/isolamento & purificação , Feminino , Cefaleia/etiologia , Humanos , Contagem de Leucócitos , Linezolida/farmacologia , Linezolida/uso terapêutico , Meningite/tratamento farmacológico , Meningite/microbiologia , Testes de Sensibilidade Microbiana
14.
Handb Clin Neurol ; 152: 117-122, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29604970

RESUMO

Central nervous system infection by Toxoplasma gondii, or Toxoplasma encephalitis, is the most common cause of brain mass lesions in human immunodeficiency virus (HIV)-infected patients. It usually presents as one or more brain abscesses, but it can also cause a diffuse encephalitis or ventriculitis. Individuals who are Toxoplasma immunoglobulin G-seropositive, who have peripheral blood CD4+ T-cell concentrations below 200/µL, are not on antiretroviral therapy, and are not taking trimethoprim-sulfamethoxazole to prevent Pneumocystis pneumonia, are at particular risk for Toxoplasma encephalitis. Neuroimaging typically shows round, isodense or hyperdense lesions in the hemispheric gray-white junction, deep white matter, or basal ganglia that enhance with contrast in a ring, nodular, or homogeneous pattern. In appropriate patients, response to an empiric treatment trial can establish the diagnosis. Immune reconstitution inflammatory syndrome is uncommon in HIV-infected patients treated for Toxoplasma encephalitis and combination antiretroviral therapy is an integral part of toxoplasmosis treatment.


Assuntos
Infecções por HIV/epidemiologia , Toxoplasma , Toxoplasmose Cerebral/epidemiologia , Animais , Antirretrovirais/uso terapêutico , Infecções do Sistema Nervoso Central/diagnóstico , Infecções do Sistema Nervoso Central/tratamento farmacológico , Infecções do Sistema Nervoso Central/epidemiologia , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Humanos , Toxoplasmose/diagnóstico , Toxoplasmose/tratamento farmacológico , Toxoplasmose/epidemiologia , Toxoplasmose Cerebral/diagnóstico , Toxoplasmose Cerebral/tratamento farmacológico
15.
New Microbiol ; 41(2): 165-167, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29384559

RESUMO

Brucellosis is the most common zoonosis in the world and it is caused by ingestion of foods contaminated by Brucella spp. that is able to avoid the immune system and can involve every organ system. The bacteria may affect the Central Nervous System (CNS) directly or using phagocytic cells with the way of the "Trojan Horse Model". Meningitis is the most common form of neuro-brucellosis (NB) but other neurological manifestation, with variable onset, such as severe encephalic involvement, neuropathy, vascular damage, radiculitis and hydrocephalus might happened. NB may manifest itself with an acute or chronic onset and could be the only manifestation of the infection or appearance during the systemic disease. Frequently the diagnosis might be very difficult and the clinical characteristics and the microbiological demonstration in the blood and in the CSF are necessary. The prognosis of brucella meningitis is generally better than other forms of chronic meningitis except for encephalitis or spinal cord involvement. The treatment is based on the combination of two or three antibiotics to achieve normalization of the cerebrospinal fluid parameters otherwise relapse are relatively frequent. We describe an atypical case of brucellar meningitis with many stroke-like signs, think as recurrent cerebrovascular events and treated with antithrombotic therapy, but without meningeal syndrome.


Assuntos
Brucelose/microbiologia , Brucelose/patologia , Infecções do Sistema Nervoso Central/microbiologia , Infecções do Sistema Nervoso Central/patologia , Antibacterianos/uso terapêutico , Brucelose/tratamento farmacológico , Infecções do Sistema Nervoso Central/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade
16.
Rev Esp Quimioter ; 31(1): 1-12, 2018 Feb.
Artigo em Espanhol | MEDLINE | ID: mdl-29390599

RESUMO

Central nervous system (CNS) infections caused by pathogens with a reduced sensitivity to drugs are a therapeutic challenge. Transport of fluid and solutes is tightly controlled within CNS, where vasculature exhibits a blood-brain barrier (BBB).The entry of drugs, including antibiotics, into the cerebro-spinal fluid (CSF) is governed by molecular size, lipophilicity, plasma protein binding and their affinity to transport systems at the BBB. The ratio of the AUCCSF (Area under the curve in CSF)/AUCS (Area under the curve in serum) is the most accurate parameter to characterize drug penetration into the CSF. Linezolid, some fluoroquinolones and metronidazole get high CSF concentrations and are useful for treating susceptible pathogens. Some highly active antibiotic compounds with low BBB permeability can be directly administered into the ventricles together with concomitant intravenous therapy. The ideal antibiotic to treat CNS infections should be that with a small moderately lipophilic molecule, low plasma protein binding and low affinity to efflux pumps at BBB. Knowledge of the pharmacokinetics and pharmacodynamics of antibiotics at the BBB will assist to optimize antibiotic treatment in CNS infections. This article reviews the physicochemical properties of the main groups of antibiotics to assess which compounds are most promising for the treatment of CNS infections and how to use them in the daily clinical practice.


Assuntos
Antibacterianos/farmacocinética , Sistema Nervoso Central/metabolismo , Animais , Antibacterianos/uso terapêutico , Barreira Hematoencefálica , Infecções do Sistema Nervoso Central/tratamento farmacológico , Infecções do Sistema Nervoso Central/metabolismo , Difusão , Humanos
17.
Curr Opin Infect Dis ; 31(1): 57-68, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29293475

RESUMO

PURPOSE OF REVIEW: The barriers surrounding the central nervous system (CNS) together with the emergence of multiresistant pathogens pose a therapeutic challenge for the effective treatment of CNS infections. RECENT FINDINGS: In addition to vancomycin, colistin and aminoglycosides, classically used for intrathecal injection, drug concentrations in cerebrospinal fluid after intrathecal injection of daptomycin and tigecyclin were recently studied. SUMMARY: The entry of antiinfectives into the CNS compartments is determined by the physicochemical properties of the drug and by conditions in the host. The most important drug properties are lipophilicity at a neutral pH, molecular mass and drug binding to serum proteins. In clinical practice, active transport is of importance only for some drugs. In recent years, intrathecal injection of antiinfectives in addition to systemic therapy has regained attention as a means to achieve high cerebrospinal fluid concentrations. The classification of antibacterials and antifungals into time-dependent and concentration-dependent compounds is also valid for the CNS compartments.


Assuntos
Antibacterianos/farmacologia , Antibacterianos/farmacocinética , Infecções Bacterianas/tratamento farmacológico , Infecções do Sistema Nervoso Central/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Antibacterianos/química , Humanos , Injeções Espinhais , Pessoa de Meia-Idade , Adulto Jovem
18.
Acta Neurochir (Wien) ; 160(3): 487-496, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29356895

RESUMO

Spinal infection (SI) is defined as an infectious disease affecting the vertebral body, the intervertebral disc, and/or adjacent paraspinal tissue and represents 2-7% of all musculoskeletal infections. There are numerous factors, which may facilitate the development of SI including not only advanced patient age and comorbidities but also spinal surgery. Due to the low specificity of signs, the delay in diagnosis of SI remains an important issue and poor outcome is frequently seen. Diagnosis should always be supported by clinical, laboratory, and imaging findings, magnetic resonance imaging (MRI) remaining the most reliable method. Management of SI depends on the location of the infection (i.e., intraspinal, intervertebral, paraspinal), on the disease progression, and of course on the patient's general condition, considering age and comorbidities. Conservative treatment mostly is reasonable in early stages with no or minor neurologic deficits and in case of severe comorbidities, which limit surgical options. Nevertheless, solely medical treatment often fails. Therefore, in case of doubt, surgical treatment should be considered. The final result in conservative as well as in surgical treatment always is bony fusion. Furthermore, both options require a concomitant antimicrobial therapy, initially applied intravenously and administered orally thereafter. The optimal duration of antibiotic therapy remains controversial, but should never undercut 6 weeks. Due to a heterogeneous and often comorbid patient population and the wide variety of treatment options, no generally applicable guidelines for SI exist and management remains a challenge. Thus, future prospective randomized trials are necessary to substantiate treatment strategies.


Assuntos
Infecções do Sistema Nervoso Central/terapia , Doenças da Coluna Vertebral/terapia , Antibacterianos/uso terapêutico , Infecções do Sistema Nervoso Central/diagnóstico por imagem , Infecções do Sistema Nervoso Central/tratamento farmacológico , Infecções do Sistema Nervoso Central/microbiologia , Humanos , Imagem por Ressonância Magnética , Doenças da Coluna Vertebral/diagnóstico por imagem , Doenças da Coluna Vertebral/tratamento farmacológico , Doenças da Coluna Vertebral/microbiologia
20.
Eur J Drug Metab Pharmacokinet ; 43(1): 45-53, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28616823

RESUMO

BACKGROUND AND OBJECTIVE: For patients with intracranial infection, local intrathecal administration of meropenem may be a useful method to obtain a sufficient drug concentration in the cerebral spinal fluid (CSF). However, a large inter-individual variability may pose treatment efficacy at risk. This study aimed to identify factors affecting drug concentration in the CSF using population pharmacokinetics method. METHODS: After craniotomy, aneurysm patients with an indwelling lumbar cistern drainage tube who received a combined intravenous and intrathecal administration of meropenem for the treatment of suspected intracranial infection were enrolled. Venous blood and CSF specimens were collected for determining meropenem concentrations. Nonlinear mixed-effects modeling method was used to fit blood and CSF concentrations simultaneously and to develop the population pharmacokinetic model. The proposed model was applied to simulate dosage regimens. RESULTS: A three-compartmental model was established to describe meropenem in vivo behavior. Lumbar CSF drainage resulted in a drug loss, and drug clearance in CSF (CLCSF) was employed to describe this. The covariate analysis found that the drainage volume (mL/day) was strongly associated with CLCSF, and the effect of creatinine clearance was significant on the clearance of meropenem in blood (CL). Visual predictive check suggested that the proposed pharmacokinetic model agreed well with the observations. Simulation showed that both intravenous and intrathecal doses should be increased with the increases of minimum inhibitory concentration and daily CSF drainage volume. CONCLUSION: This model incorporates covariates of the creatinine clearance and the drainage volume, and a simple to use dosage regimen table was created to guide clinicians with meropenem dosing.


Assuntos
Aneurisma/complicações , Infecções do Sistema Nervoso Central/tratamento farmacológico , Craniotomia/efeitos adversos , Tienamicinas/administração & dosagem , Tienamicinas/farmacocinética , Administração Intravenosa , Adulto , Idoso , Aneurisma/sangue , Aneurisma/líquido cefalorraquidiano , Aneurisma/cirurgia , Antibacterianos/administração & dosagem , Antibacterianos/sangue , Antibacterianos/líquido cefalorraquidiano , Antibacterianos/farmacocinética , Infecções do Sistema Nervoso Central/sangue , Infecções do Sistema Nervoso Central/líquido cefalorraquidiano , Infecções do Sistema Nervoso Central/complicações , Feminino , Humanos , Injeções Espinhais , Masculino , Meropeném , Pessoa de Meia-Idade , Modelos Biológicos , Tienamicinas/sangue , Tienamicinas/líquido cefalorraquidiano , Adulto Jovem
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