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Hyponatremia is the most frequent electrolyte imbalance in geriatric medicine. Causes of hyponatremia were retrospectively analyzed in all in-patients treated in 2016 (Nâ¯= 2267, 1564 women, 703 men, mean age ± standard deviation 81.9⯱ 7.6 years). Any form of hyponatremia on admission, during the stay or on discharge was noted in 308 patients (13.6%, 231 women, 77 men; mean age ± standard deviation 83.1⯱ 7.3 years, pâ¯= 0.009 vs. age of all patients). Women had a higher probability of developing hyponatremia compared to men (pâ¯= 0.019), 131 patients were hypovolemic, and dyspnea as an indicator of hypervolemia was noted in 71 patients.Only 12 patients suffering from hyponatremia (3.9%) did not receive any of the potentially sodium-lowering drugs assessed (diuretics, angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, antidepressants, neuroleptics, nonsteroidal antirheumatics, carbamazepine, oxcarbazepine). The median number of drugs per patient potentially lowering the plasma sodium level was 3 and the maximum number was 7.Hypovolemic hyponatremia and the syndrome of inadequate antidiuretic hormone secretion were the most important causes of hyponatremia. Adverse drug effects were the main origins of both conditions. In patients with hyponatremia the drug load influencing plasma sodium level should be minimized, thiazide diuretics should be avoided and older individuals should receive a diet with sufficient salt content.
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BACKGROUND: Gum arabic, a polysaccharide exudate from Acacia senegal (L.) Willdenow trees, has already been used by African native people in natural medicine. METHODS: Using whole-blood samples from young (20-35 years) and older (>80 years) healthy volunteers (each group n = 10), the effect of an aqueous solution of GA on phagocytosis of Escherichia coli was examined with a gentamicin protection assay. Whole-blood samples of each volunteer were stimulated with GA and as a control with CpG oligodeoxynucleotides (Toll-like receptor -9 agonists) for 2 h, then co-incubated with E. coli for 30 min and thereafter treated with gentamicin for up to 240 min to kill extracellular bacteria. Then, whole-blood cells were lysed with distilled water, and colony-forming units were counted by quantitative plating. Cytokine enzyme-linked immunosorbent assay for the detection of TNF-α and IL-6 was performed using the blood supernatant. RESULTS: The GA concentration tested (20 mg/mL) did not affect the viability of eukaryotic cells. Phagocytosis of E. coli by whole-blood leukocytes derived from young (p = 0.008) and older (p = 0.004) healthy volunteers was increased by 120.8% (young) and 39.2% (old) after stimulation with GA. In contrast, CpG only stimulated the bacterial phagocytosis by cells derived from young volunteers (p = 0.004). Stimulation of whole blood with GA increased the intracellular killing of E. coli in young (p = 0.045) and older volunteers (p = 0.008) and induced a TNF-α release in whole blood collected from older volunteers but not from younger ones (p = 0.008). CONCLUSIONS: These data encourage the isolation of active compounds of GA and the initiation of clinical trials addressing the preventive effect of GA on bacterial infections.
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Key Clinical Message: Hypophyseal dysfunction may be overlooked by the currently generally accepted laboratory routine for the differential diagnosis in patients suffering from symptoms of depression or dementia. Abstract: Hypothyroidism is an important cause of depression and potentially reversible cognitive impairment. Whereas the determination of the plasma concentration of thyrotropin (TSH) is generally considered part of the laboratory screening tests for dementia, the measurement of total or free triiodothyronine (T3, FT3), thyroxine (T4, FT4) and cortisol in plasma does not belong to the routine diagnostic workup in patients with depression or suspected dementia. In an 87-year-old lady suffering from increasingly poor general health, decreased fluid and food intake, mood depression and lack of energy, three measurements of plasma TSH produced normal values. A cranial computed tomography (cCT) 2 days prior to hospital admission had been assessed as apparently normal. A second cCT performed following a loss of consciousness complicated by tongue bite showed a hypophyseal tumor. Then, low plasma levels of FT3, FT4 and cortisol were found. Following hormone replacement and transsphenoidal tumor resection, the patient recovered rapidly. The present case report illustrates the pitfalls of measuring merely the TSH level in the detection of thyroid and hypophyseal dysfunction.
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INTRODUCTION: Streptococcus pneumoniae is the most common cause of bacterial meningitis and meningoencephalitis in humans. The bacterium produces numerous virulence determinants, among them hydrogen peroxide (H2O2) and pneumolysin (Ply), which contribute to bacterial cytotoxicity. Microglia, the resident phagocytes in the brain, are distinct from other macrophages, and we thus compared their susceptibility to pneumococcal toxicity and their ability to phagocytose pneumococci with those of bone marrow-derived macrophages (BMDM). METHODS: Microglia and BMDM were co-incubated with S. pneumoniae D39 to analyze survival of phagocytes by fluorescence microscopy, bacterial growth by quantitative plating, and phagocytosis by an antibiotic protection assay. Ply was detected by hemolysis assay and Western blot analysis. RESULTS: We found that microglia were killed during pneumococcal infection with a wild-type and an isogenic ply-deficient mutant, whereas viability of BMDM was not affected by pneumococci. Treatment with recombinant Ply showed a dose-dependent cytotoxic effect on microglia and BMDM. However, high concentrations of recombinant Ply were required and under the chosen experimental conditions, Ply was not detectable in the supernatant during infection of microglia. Inactivation of H2O2 by exogenously added catalase abolished its cytotoxic effect. Consequently, infection of microglia with pneumococci deficient for the pyruvate oxidase SpxB, primarily producing H2O2, resulted in reduced killing of microglia. CONCLUSION: Taken together, in the absence of Ply, H2O2 caused cell death in primary phagocytes in concentrations produced by pneumococci.
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Nosocomial central nervous system (CNS) infections with carbapenem- and colistin-resistant Gram-negative and vancomycin-resistant Gram-positive bacteria are an increasing therapeutic challenge. Here, we review pharmacokinetic and pharmacodynamic data and clinical experiences with new antibiotics administered intravenously for the treatment of CNS infections by multi-resistant bacteria. Cefiderocol, a new siderophore extended-spectrum cephalosporin, pharmacokinetically behaves similar to established cephalosporins and at high doses will probably be a valuable addition in our therapeutic armamentarium for CNS infections. The new glycopeptides dalbavancin, telavancin, and oritavancin are highly bound to plasma proteins. Although effective in animal models of meningitis, it is unlikely that they reach effective cerebrospinal fluid (CSF) concentrations after intravenous administration alone. The ß-lactam/ß-lactamase inhibitor combinations have the principal problem that both compounds must achieve adequate CSF concentrations. In the commercially available combinations, the dose of the ß-lactamase inhibitor tends to be too low to achieve adequate CSF concentrations. The oxazolidinone tedizolid has a broader spectrum but a less suitable pharmacokinetic profile than linezolid. The halogenated tetracycline eravacycline does not reach CSF concentrations sufficient to treat colistin-resistant Gram-negative bacteria with usual intravenous dosing. Generally, treatment of CNS infections should be intravenous, whenever possible, to avoid adverse effects of intraventricular therapy (IVT). An additional IVT can overcome the limited penetration of many new antibiotics into CSF. It should be considered for patients in which the CNS infection responds poorly to systemic antimicrobial therapy alone.
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BACKGROUND: Poliomyelitis is an infectious disease of the peripheral motor neurons, which predominantly affects children and causes residual palsies. Because of the oral poliomyelitis vaccination started in Germany in 1960 and 1962 and the following rapid decline of the incidence of this infection, the postpolio syndrome in Germany is a disease of older people. METHODS: Since 2008, we have offered a poliomyelitis outpatient consultation at the Center of Geriatrics, Protestant Hospital Göttingen-Weende and have treated 33 patients. RESULTS: The spectrum of persistent deficits after poliomyelitis ranges from palsy of single extremities to severe disability with (temporary) ventilator dependence. Many patients suffer from scoliosis or shortening of limbs of different degrees, which promotes degenerative diseases of the spinal cord and joints with secondary myelopathy, injury of spinal nerve roots or peripheral nerves or respiratory failure. The postpolio syndrome is characterized by an increase of the functional deficits after decades of compensation. The palsies of 2 of the 33 patients were not caused by poliomyelitis but by myelomeningocele and schizencephaly, respectively. CONCLUSION: The motor deficits acquired in childhood enable the majority of the patients to successfully master their lives. Because of the limited compensatory capacities of postpolio patients, even small increases in the severity of the palsy can cause a severe decline of the functional status and an impairment of the ability to live an independent life. In a substantial proportion of patients with the diagnosis poliomyelitis the symptoms are caused by other diseases.
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Poliomielite , Humanos , Masculino , Feminino , Idoso , Poliomielite/diagnóstico , Síndrome Pós-Poliomielite/diagnóstico , Síndrome Pós-Poliomielite/complicações , Diagnóstico Diferencial , Alemanha , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , EncéfaloRESUMO
INTRODUCTION: The central nervous system is frequently involved during severe sepsis. Patients either develop septic encephalopathy characterized by delirium and coma or focal neurological signs as a consequence of septic-embolic or septic-metastatic encephalitis. AREAS COVERED: In this review, a summary of currently available literature on established and some promising experimental treatment options for septic encephalopathy and encephalitis is provided, with a focus on the clinical utility of published studies. EXPERT OPINION: Treatment relies on proper identification of the causative pathogen and rapidly initiated adequate empirical or (after identification of the pathogen) tailored antibiotic therapy, fluid and electrolyte management. In the presence of brain abscess(es) or mycotic aneurysm(s), surgery or interventional neuroradiology must be considered. Pharmacological approaches to prevent delirium of different etiology include the use of dexmedetomidine and (with limitations) of melatonin and its derivatives. In the absence of a specific pharmacological treatment, non-pharmacological bundles of interventions (e.g. promotion of sleep, cognitive stimulation, early mobilization and adequate therapy of pain) are of proven efficacy to prevent delirium of different etiology including sepsis. Experimental promising therapies include the use of non-bacteriolytic antibiotics and the reduction of the toxic effects of microglial activation.
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Delírio , Encefalite , Sepse , Humanos , Encefalite/complicações , Encefalite/terapia , Sepse/complicações , Sepse/terapia , Sepse/diagnóstico , Sistema Nervoso Central/patologiaRESUMO
Next to acute sickness behavior, septic encephalopathy is the most frequent involvement of the brain during infection. It is characterized by a cross-talk of pro-inflammatory cells across the blood-brain barrier, by microglial activation and leukocyte migration, but not by the entry of infecting organisms into the brain tissue. Septic encephalopathy is very frequent in older persons because of their limited cognitive reserve. The predominant clinical manifestation is delirium, whereas focal neurological signs and symptoms are absent. Electroencephalography is a very sensitive method to detect functional abnormalities, but these abnormalities are not specific for septic encephalopathy and of limited prognostic value. Routine cerebral imaging by computer tomography usually fails to visualize the subtle abnormalities produced by septic involvement of the brain. Magnetic resonance imaging is by far more sensitive to detect vasogenic edema, diffuse axonal injury or small ischemic lesions. Routine laboratory parameters most suitable to monitor sepsis, but not specific for septic encephalopathy, are C-reactive protein and procalcitonin. The additional measurement of interleukin (IL)-6, IL-8, IL-10 and tumor necrosis factor-α increases the accuracy to predict delirium and an unfavorable outcome. The most promising laboratory parameters to quantify neuronal and axonal injury caused by septic encephalopathy are neurofilament light chains (NfL) and S100B protein. Neuron-specific enolase (NSE) plasma concentrations are strongly influenced by hemolysis. We propose to determine NSE only in non-hemolytic plasma or serum samples for the estimation of outcome in septic encephalopathy.
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Background: Urinary tract infections are a major cause of the consumption of antibiotics in humans. Methods: We studied the effect of a vaccine (StroVac®, containing inactivated bacteria and used to prevent recurrent urinary tract infections) licensed in Germany on the release of pro-inflammatory cytokines and the phagocytosis of Escherichia (E.) coli in primary murine macrophages and the macrophage cell line J774A.1. Results: StroVac® increased the release of the cytokines TNF-α, IL-6, IL-12/23 p40, and IL-1ß and stimulated the phagocytosis of E. coli in a dose-dependent manner. This effect was independent of LPS as shown by the use of macrophages isolated from LPS-resistant C3H/HeJ mice. At concentrations up to 30 mg/l it was not toxic to bacteria or eukaryotic cells. Conclusion: StroVac® does not only act via the adaptive but also by stimulating the innate immune system. This stimulation may help to build trained innate immunity against bacterial pathogens involved in recurrent urinary tract infections.
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Escherichia coli , Infecções Urinárias , Humanos , Animais , Camundongos , Camundongos Endogâmicos C3H , Lipopolissacarídeos , Macrófagos , Vacinação , Infecções Urinárias/prevenção & controle , Bactérias , CitocinasRESUMO
INTRODUCTION: The incidence of community-acquired acute bacterial meningitis has decreased during the last decades. However, outcome remains poor with a significant proportion of patients not surviving and up to 50% of survivors suffering from long-term sequelae. These guidelines were developed by the Deutsche Gesellschaft für Neurologie (DGN) under guidance of the Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF) to guide physicians through diagnostics and treatment of adult patients with acute bacterial meningitis. RECOMMENDATIONS: The most important recommendations are: (i) In patients with suspected acute bacterial meningitis, we recommend that lumbar cerebrospinal fluid (with simultaneous collection of serum to determine the cerebrospinal fluid-serum glucose index and blood cultures) is obtained immediately after the clinical examination (in the absence of severely impaired consciousness, focal neurological deficits, and/or new epileptic seizures). (ii) Next, we recommend application of dexamethasone and empiric antibiotics intravenously. (iii) The recommended initial empiric antibiotic regimen consists of ampicillin and a group 3a cephalosporin (e.g., ceftriaxone). (iv) In patients with severely impaired consciousness, new onset focal neurological deficits (e.g. hemiparesis) and/or patients with newly occurring epileptic seizures, we recommend that dexamethasone and antibiotics are started immediately after the collection of blood; we further recommend that -if the imaging findings do not indicate otherwise -a lumbar CSF sample is taken directly after imaging. (v) Due to the frequent occurrence of intracranial and systemic complications, we suggest that patients with acute bacterial meningitis are treated at an intensive care unit in the initial phase of the disease. In the case of impaired consciousness, we suggest that this is done at an intensive care unit with experience in the treatment of patients with severe CNS diseases. CONCLUSIONS: The German S2k-guidelines give up to date recommendations for workup, diagnostics and treatment in adult patients with acute bacterial meningitis.
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Understanding the factors that determine the luminescence lifetime of transition metal compounds is key for applications in photocatalysis and photodynamic therapy. Here we show that for [ Ru ( bpy ) 3 ] 2 + ${[{\rm{Ru}}({\rm{bpy}})_{\rm{3}} ]^{{\rm{2 + }}} }$ (bpy = 2,2'-bipyridine), the generally accepted idea that emission lifetimes can be controlled optimizing the energy barrier from the emissive triplet metal-to-ligand charge-transfer (3 MLCT) state to the thermally-activated triplet metal-centered (3 MC) state or the energy gap between both states is a misconception. Further, we demonstrate that considering a single relaxation pathway determined from the minimum that is lowest in energy leads to wrong temperature-dependent emission lifetimes predictions. Instead, we obtain excellent agreement with experimental temperature-dependent lifetimes when an extended kinetic model that includes all the pathways related to multiple Jahn-Teller isomers and their effective reaction barriers is employed. These concepts are essential to correctly design other luminescent transition metal complexes with tailored emission lifetimes based on theoretical predictions.
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Leukopenia, including agranulocytosis, is a severe complication of treatment with all ß-lactam antibiotics. Its incidence increases with age. Cardiobacterium hominis endocarditis after implantation of an aortic valve bio-prosthesis in a 77-year-old woman was treated with ceftriaxone 2 g/day plus gentamicin 160 mg/day intravenously. On Day 25 of treatment, blood leukocytes had decreased to 1800/µl (neutrophils 370/µl). Antibiotic therapy was switched to penicillin G 20 million international units (IU)/day. Thereafter, blood leukocytes including neutrophils normalized suggesting that penicillin G was less bone marrow-toxic than ceftriaxone. High-dose ciprofloxacin, the alternative to penicillin G, was avoided because of the risk of cognitive and behavioral side effects. The present case suggests that with close laboratory monitoring a ß-lactam with differing side chains should not be considered contraindicated after ß-lactam antibiotic-induced neutropenia.
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Geriatric traumatological rounds (GTR) with representatives of several disciplines are a challenge in the setting of primary care hospitals with limited resources. The GTR were started with only an experienced traumatologist and a geriatrician in 2019. Routine quality control data showed a reduction of the frequency of cardiac failure and mortality after the start of the GTR. Therefore, even the minimum variant of GTR with the focus on the differential diagnosis of falls and adequate drug treatment appears to be beneficial for the patient. Special attention is given to the medical treatment of cardiac failure, pulmonary diseases, osteoporosis, psychiatric disorders and anemia. Vitamin B12 and folate deficiency are substituted. When anticoagulants or platelet aggregation inhibitors are indicated, they are resumed early. Potentially inadequate drugs for older patients are avoided. Doses of many drugs used in geriatric patients must be adjusted to a reduced renal function often present in old age. Frequent electrolyte abnormalities are diagnosed and adequately treated.
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Anemia , Insuficiência Cardíaca , Humanos , Idoso , Anemia/induzido quimicamente , Anticoagulantes/efeitos adversos , Insuficiência Cardíaca/induzido quimicamente , Atenção Primária à Saúde , HospitaisRESUMO
BACKGROUND: In the 19th century, neurosyphilis was the most frequent cause of dementia in Western Europe. Now dementia caused by syphilis has become rare in Germany. We studied whether routine testing of patients with cognitive abnormalities or neuropathy for antibodies against Treponema pallidum has therapeutic consequences in geriatric patients. METHODS: A Treponema pallidum electrochemiluminescence immunoassay (TP-ECLIA) is routinely performed in all in-patients treated at our institution with cognitve decline or neuropathy and no or insufficient previous diagnostic workup. Patients with a positive TP-ECLIA treated from October 2015 to January 2022 (76 months) were retrospectively evaluated. In cases of positive TP-ECLIA, further specific laboratory investigations were performed to assess whether antibiotic therapy was indicated. RESULTS: In 42 of 4116 patients (1.0%), TP-ECLIA detected antibodies directed against Treponema in serum. Specifity of these antibodies was ensured by immunoblot in 22 patients (11 × positiv, 11 × borderline values). Treponema-specific IgM was detectable in the serum of one patient, in 3 patients the Rapid Plasma Reagin (RPR) test, a modified Venereal Disease Research Laboratory test (VDRL), in serum was positiv. CSF analysis was performed in 10 patients. One patient had CSF pleocytosis. In 2 other patients, the Treponema-specific IgG antibody index was elevated. 5 patients received antibiotic therapy (4 × ceftriaxone 2 g/d i.v., 1 × doxycycline 300 mg/d p.o.). CONCLUSION: In approx. 1 of patients with previously undiagnosed or not sufficiently diagnosed cognitive decline or neuropathy, the diagnostic workup for active syphilis resulted in a course of antibiotic treatment.
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Disfunção Cognitiva , Demência , Polineuropatias , Sífilis , Humanos , Idoso , Sífilis/complicações , Sífilis/diagnóstico , Sífilis/tratamento farmacológico , Diagnóstico Diferencial , Estudos Retrospectivos , Treponema pallidum , Polineuropatias/diagnóstico , Antibacterianos , Disfunção Cognitiva/diagnóstico , Demência/diagnósticoRESUMO
The cerebrospinal fluid (CSF) space is convoluted. CSF flow oscillates with a net flow from the ventricles towards the cerebral and spinal subarachnoid space. This flow is influenced by heartbeats, breath, head or body movements as well as the activity of the ciliated epithelium of the plexus and ventricular ependyma. The shape of the CSF space and the CSF flow preclude rapid equilibration of cells, proteins and smaller compounds between the different parts of the compartment. In this review including reinterpretation of previously published data we illustrate, how anatomical and (patho)physiological conditions can influence routine CSF analysis. Equilibration of the components of the CSF depends on the size of the molecule or particle, e.g., lactate is distributed in the CSF more homogeneously than proteins or cells. The concentrations of blood-derived compounds usually increase from the ventricles to the lumbar CSF space, whereas the concentrations of brain-derived compounds usually decrease. Under special conditions, in particular when distribution is impaired, the rostro-caudal gradient of blood-derived compounds can be reversed. In the last century, several researchers attempted to define typical CSF findings for the diagnosis of several inflammatory diseases based on routine parameters. Because of the high spatial and temporal variations, findings considered typical of certain CNS diseases often are absent in parts of or even in the entire CSF compartment. In CNS infections, identification of the pathogen by culture, antigen detection or molecular methods is essential for diagnosis.
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Infecções do Sistema Nervoso Central , Encéfalo/fisiologia , Infecções do Sistema Nervoso Central/líquido cefalorraquidiano , Ventrículos Cerebrais , Epêndima , Humanos , Medula EspinalRESUMO
OBJECTIVES: Many patients receive benzodiazepines or Z-drugs during hospitalisation due to sleeping problems. In a pilot study, we aimed to find out whether, and to what degree, a multi-faceted intervention can reduce the use of these drugs, especially in older patients and those without a psychiatric or neurological disorder. The results of this pilot study should inform the design of a randomised controlled trial (RCT). METHODS: In a quasi-experimental design, we implemented the intervention in a German hospital with the support of the hospital director, medical and nursing staff and employee representatives. We compared prescription data for sleep-inducing drugs before and after the intervention by Fisher's exact test and used odds ratios (ORs) with their 95% CIs as a measure of effect size. RESULTS: The data from 960 patients aged ≥65 years before intervention and 1049 patients after intervention were analysed. Before intervention, 483 (50.3%) of the patients received sleep-inducing drugs at some time during their hospital stay. After the intervention, 381 (36.3%) patients received a sleep-inducing drug, resulting in an OR of 0.56 (95% CI 0.47 to 0.68) (p<0.001). The reduction was particularly pronounced in patients without a psychiatric or neurological disorder (from 45.0% to 28.8%). In particular, the consumption of benzodiazepines declined from 24.3% to 8.5% (OR 0.31; 95% CI 0.23 to 0.4) (p<0.001). CONCLUSIONS: A multi-faceted intervention to change the practice of the use of sleep-inducing drugs in one hospital was successful in terms of drug reduction, particularly for benzodiazepines. The intervention was effective especially for target persons-that is, those without a psychiatric or neurological disease. Awareness of the magnitude of the change and the role of important stakeholders could help researchers and hospital staff to design a large RCT, including control hospitals, to evaluate the success of a multi-faceted intervention on a scientifically sound basis.
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Background: In patients with Alzheimer's disease (AD), bacterial infections are often associated with a cognitive decline. Animal models of genuine acute infections with viable bacteria which induce deterioration of neurodegenerative diseases are missing. Objective: We assessed the effect of an intracerebral infection with E. coli in a mouse model of AD. Methods: 13-month-old Tg2576 +/- mice and transgene negative littermates (Tg2576 -/-) received an intracerebral injection with E. coli K1 or saline followed by treatment with ceftriaxone starting 41 h post infection (p.i.) for 5 days. For 4 weeks, mice were monitored for clinical status, weight, motor functions, and neuropsychological status using the Morris water maze. ELISAs, stainings, and immunohistochemistry in brains were performed at the end of the experiment. Results: Mortality of the infection was approximately 20%. After 4 weeks, spatial learning of infected Tg2576 +/- mice was compromised compared to non-infected Tg2576 +/- mice (pâ<â0.05). E. coli infection did not influence spatial learning in Tg2576 -/- mice, or spatial memory in both Tg2576 +/- and -/- mice within 4 weeks p.i.. Necrosis of hippocampal neurons was induced in infected compared to non-infected Tg2576 +/- mice 4 weeks p.i., whereas brain concentrations of Aß1-40, Aß1-42, and phosphoTau as well as axonal damage and microglia density were not altered. Conclusion: Here, we proved in principle that a genuine acute bacterial infection can worsen cognitive functions of AD mice. Mouse models of subacute systemic infections are needed to develop new strategies for the treatment of bacterial infections in patients with AD in order to minimize their cognitive decline.
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The outcome of chronic meningitis depends to a large degree on the causative pathogen and the interval between onset of symptoms and diagnosis. We present a patient with a delayed diagnosis and several complications, for whom adequate therapy resulted in a favorable outcome. In a 76-year-old male patient, Candida albicans meningitis was diagnosed 4 months after the onset of symptoms. CSF findings (protein >1000 mg/L, predominance of intrathecal immunoglobulin A synthesis, lactate concentrations of approx. 10 mmol/L, leukocyte counts around 1000/µl, variable differential leukocyte counts) resembled tuberculous meningitis. In spite of the long interval without treatment, voriconazole 200 mg every 12 h for 7 weeks followed by fluconazole 300 mg/day maintenance therapy for 7 months led to a recovery with only mild deficits. The case illustrates that 1. C. albicans can cause chronic meningitis in patients without severe immune defects, 2. patients can survive C. albicans meningitis with mild long-term sequelae even when diagnosis and adequate treatment are delayed, and 3. voriconazole as a sole agent may be suitable for treatment of C. albicans meningitis.
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INTRODUCTION: Interferon-γ levels are increased upon viral infections and during inflamm-aging. Resistance to infections due to Escherichia coli (E. coli), a major cause of bacteriaemia and sepsis, is impaired in aged individuals, partly due to altered phagocytic capacity and cytokine release of immune cells. Here, we analyzed the effect of IFN-γ on phagocytosis of E. coli K1 and release of proinflammatory cytokines by macrophages in resting condition and upon stimulation with different bacterial Toll-like receptor (TLR) agonists. METHODS: Primary peritoneal macrophages from C57BL/6 mice were exposed to medium or stimulated with agonists of TLR4 (LPS), 1/2 (Pam3CSK4), and 9 (CpG-DNA) in the presence and absence of IFN-γ (100 U/ml) for 24 h. TNF-α, IL-6, and KC were measured in the cell culture supernatant by ELISA. Macrophages were exposed to viable E. coli K1. After 90 min, intracellular phagozytosed bacteria were quantified by quantitative plating. RESULTS: Macrophages treated with LPS 1 µg/ml in the presence of IFN-γ ingested more than 10-fold lower numbers of E. coli than macrophages treated with LPS alone. Phagocytosis of E. coli by macrophages in resting condition or upon stimulation with Pam3CSK4 or CpG was not significantly affected by IFN-γ. Cytokine release was differentially modulated by IFN-γ, with reduced KC release by TLR-stimulated macrophages in the presence of IFN-γ being the most striking effect. CONCLUSIONS: In vitro, IFN-γ reduces the phagocytosis of E. coli by LPS-stimulated macrophages and differentially modulates cytokine release of macrophages activated by different bacterial TLR agonists. Elevated levels of IFN-γ might lead to reduced bacterial clearance and worse outcome of bacterial infections, e.g., in aged individuals and after viral infections and other inflammatory events.