The treatment of nosocomial meningitis and brain abscess by carbapenem-resistant Klebsiella pneumonia.

We report the fourth case of Carbapenem-resistant Klebsiella pneumoniae (CRKP) meningitis and the only one associated with brain abscess formation. A 29-years-old male patient developed septic shock 13 days after a right nasopharyngeal AVM resection. CRKP was grown from CSF with a MIC for meropenem ≥16 mg/L. Intravenous tigecycline and amikacin, combined with intrathecal amikacin and oral sulfamethoxazole were given. CSF culture was sterile on the 23rd day post operation. A right temporal lobe brain abscess formed by day 38 and was drained. Antibiotics were changed to oral sulfamethoxazole and minocycline for four weeks. The patient was cured with no relapse to date. With few cases reported we can only carefully recommend the combinational use of intravenous antibiotics with high dose intrathecal/intraventricular aminoglycosides.

[Long course of polymyxin B for the treatment of brain abscess caused by carbapenem resistant Acinetobacter baumannii: a case report].

The clinical efficacy of polymyxins in severe infection caused by carbapenem resistant organism (CRO) has gradually been recognized, and the course of treatment is generally 2 to 4 weeks. The most common complications after intravenous injection are nephrotoxicity and neurotoxicity, however, there are few reports on the efficacy and safety of the long course use of polymyxins. A patient with carbapenem resistant Acinetobacter baumannii (CRAB) infection after neurosurgery was admitted to the department of neurosurgical intensive care unit (NICU) of Lanzhou University Second Hospital. As the family refused the excision of brain abscess and Ommaya reservoir placement, polymyxin B was given intravenous (3.0 mg×kg-1×d-1) combined with intrathecal (5 mg once daily) injection, and high-dose sulbactam (8 g/d) was intravenously injected for anti-infection therapy. Finally, the brain abscess was absorbed and the patient was successfully cured. The total course of polymyxin B was 69 days with a cumulative dosage of 7 500 mg. There were no complications such as polymyxin-related nephrotoxicity and neurotoxicity during the period, and no symptoms of respiratory inhibition or neuromuscular blockage were observed, but polymyxin-related skin pigmentation appeared about 1 month after intravenous administration of polymyxins B, which subsided after drug withdrawal. It is suggested that long course of polymyxins B is safe and effective for intracranial infection caused by CRAB.

Precision diagnosis and therapy of a case of brain abscesses associated with asymptomatic pulmonary arteriovenous fistulas.

BACKGROUND: Brain abscesses, a severe infectious disease of the CNS, are usually caused by a variety of different pathogens, which include Streptococcus intermedius (S. intermedius). Pulmonary arteriovenous fistulas (PAVFs), characterized by abnormal direct communication between pulmonary artery and vein, are a rare underlying cause of brain abscesses. CASE PRESENTATION: The patient was a previous healthy 55-year-old man who presented with 5 days of headache and fever. Cerebral magnetic resonance imaging (MRI) suggested a brain abscess. Thoracic CT scan and angiography demonstrated PAVFs. Aiding by metagenomic next-generation sequencing (mNGS) of the cerebrospinal fluid (CSF) sample which identified S. intermedius as the causative pathogen, the patient was switched to the single therapy of large dose of penicillin G and was cured precisely and economically. CONCLUSIONS: It is an alternative way to perform mNGS to identify causative pathogens in patients with brain abscesses especially when the results of traditional bacterial culture were negative. Further thoracic CT or pulmonary angiography should also be undertaken to rule out PAVFs as the potential cause of brain abscess if the patient without any known premorbid history.

Methicillin-resistant Staphylococcus aureus intracranial abscess: An analytical series and review on molecular, surgical and medical aspects.

PURPOSE: Intracranial abscess caused by methicillin-resistant Staphylococcus aureus (MRSA) is rare and unexplored. The aim of the present study is to examine the prevalence, clinical and molecular characteristics, treatment options and outcome of MRSA intracranial abscess over a period of 6 years. PATIENTSAND METHODS: A total of 21 patients were included in this retrospective study. The demographic and clinical details of all the patients were collected. Molecular typing including staphylococcal cassette chromosome mec typing, spa typing and polymerase chain reaction of Panton-Valentine leucocidin toxin (PVL) gene for the latter 6 isolates was performed. RESULTS: The paediatric population was the most affected group (33.3%). The primary route of infection was post-operative/trauma in 7 (33.3%) cases. All the patients were treated surgically either by aspiration or excision. Fifteen (71%) patients received anti-MRSA treatment with vancomycin or linezolid, where linezolid-treated patients showed better prognosis. Of the 11 patients who were on follow-up, unfavourable outcome was observed in 3 (27.3%) cases and 8 (72.7%) cases improved. The molecular typing of six isolates revealed four community-associated (CA) MRSA, one each of livestock-associated (LA) and healthcare-associated MRSA with PVL gene noted in all. CONCLUSION: We propose that timely diagnosis, surgical intervention and appropriate anti-MRSA treatment would contribute to better outcome. The occurrence of CA-MRSA and LA-MRSA infection in the central nervous system signifies the threat from the community and livestock reservoir, thus drawing attention towards surveillance and tracking to understand the epidemiology and implement infection control measures.

Fatal thalamic abscess secondary to dental infection.

We present the case of poor neurological recovery and subsequent death secondary to a thalamic abscess in a 53-year-old man. This patient initially presented with sudden dysarthria and left hemiparesis while driving. Neuroimaging showed a multilobular abscess involving the right thalamus with oedema extending to the basal ganglionic region and brainstem. The source of the abscess was initially unknown and it required draining multiple times while the different causes were being explored. The patient's neurological state along with intubation made for a difficult and inconclusive oral examination. It was only after neuroimaging included tooth-bearing areas that it became evident that this patient had extensive periodontal disease with multiple areas of periapical radiolucencies. The patient underwent complete dental clearance alongside repeated drainage of the abscess. Despite initial postoperative improvement, the patient never recovered from the neurological damage and died 3 weeks later.

[Thalamo-mesencephalic aspergillus abscess in a heart transplant subject: a case report and literature review]. / Ascesso aspergillare talamo-mesencefalico in un soggetto sottoposto a trapianto cardiaco: caso clinico e revisione della letteratura.

Cerebral aspergillosis is a rare and highly fatal infection that mainly affects immunocompromised patients. We report on a case of a heart transplanted Caucasian man, who arrived at our hospital because of the onset of diplopy. We performed a broad diagnostic work-up: the brain MRI showed a single ring-enhancing thalamo-mesencephalic area suggestive of abscess lesion; cerebrospinal fluid (CSF) analysis disclosed galactomannan and beta-D-glucan antigens. Thus the antifungal therapy was immediately started. We decided to discontinue the therapy 16 months later because of severe hepatic toxicity, given that the patient was persistently asymptomatic, brain imaging showed a progressive resolution of the abscess area and CSF antigen analysis was persistently negative. The follow-up at three months was unchanged.

In vivo assessment of drug efficacy against Mycobacterium abscessus using the embryonic zebrafish test system.

Mycobacterium abscessus is responsible for a wide spectrum of clinical syndromes and is one of the most intrinsically drug-resistant mycobacterial species. Recent evaluation of the in vivo therapeutic efficacy of the few potentially active antibiotics against M. abscessus was essentially performed using immunocompromised mice. Herein, we assessed the feasibility and sensitivity of fluorescence imaging for monitoring the in vivo activity of drugs against acute M. abscessus infection using zebrafish embryos. A protocol was developed where clarithromycin and imipenem were directly added to water containing fluorescent M. abscessus-infected embryos in a 96-well plate format. The status of the infection with increasing drug concentrations was visualized on a spatiotemporal level. Drug efficacy was assessed quantitatively by measuring the index of protection, the bacterial burden (CFU), and the number of abscesses through fluorescence measurements. Both drugs were active in infected embryos and were capable of significantly increasing embryo survival in a dose-dependent manner. Protection from bacterial killing correlated with restricted mycobacterial growth in the drug-treated larvae and with reduced pathophysiological symptoms, such as the number of abscesses within the brain. In conclusion, we present here a new and efficient method for testing and compare the in vivo activity of two clinically relevant drugs based on a fluorescent reporter strain in zebrafish embryos. This approach could be used for rapid determination of the in vivo drug susceptibility profile of clinical isolates and to assess the preclinical efficacy of new compounds against M. abscessus.

Biodegradable drug-eluting poly[lactic-co-glycol acid] nanofibers for the sustainable delivery of vancomycin to brain tissue: in vitro and in vivo studies.

Successful treatment of a brain infection requires aspiration of the pus or excision of the abscess, followed by long-term (usually 4-8 weeks) parenteral antibiotic treatment. Local antibiotic delivery using biodegradable drug-impregnated carriers is effective in treating postoperative infections, thereby reducing the toxicity associated with parenteral antibiotic treatment and the expense involved with long-term hospitalization. We have developed vancomycin-loaded, biodegradable poly[lactic-co-glycol acid] nanofibrous membranes for the sustainable delivery of vancomycin to the brain tissue of rats by using the electrospinning technique. A high-performance liquid chromatography assay was employed to characterize the in vitro and in vivo release behaviors of pharmaceuticals from the membranes. The experimental results suggested that the biodegradable nanofibers can release high concentrations of vancomycin for more than 8 weeks in the cerebral cavity of rats. Furthermore, the membranes can cover the wall of the cavity after the removal of abscess more completely and achieve better drug delivery without inducing adverse mass effects in the brain. Histological examination also showed no inflammation reaction of the brain tissues. By adopting the biodegradable, nanofibrous drug-eluting membranes, we will be able to achieve long-term deliveries of various antibiotics in the cerebral cavity to enhance the therapeutic efficacy of cerebral infections.

[A case of cerebral abscess due to methicillin-resistant Staphylococcus aureus which is treated with linezolid + rifampin combination]. / Linezolid + rifampisin kombinasyonu ile tedavi edilen metisiline dirençli Staphylococcus aureus'un neden oldugu beyin apsesi olgusu.

Methicillin-resistant Staphylococcus aureus (MRSA) is a rare cause of cerebral abscesses, however it is a relatively more common etiologic agent in post-neurosurgical abscesses and the main antibacterial therapy option is vancomycin. In this report, a case of brain abscess due to MRSA which did not respond neither to moxifloxacin + vancomycin nor vancomycin + rifampin combination therapies, and merely treated by linezolid + rifampin combination, has been presented. Fifty-one years old female patient who was operated 40 days ago for subarachnoid bleeding and aneurysm in middle cerebral artery bifurcation, was hospitalized due to purulent leakage from the operation area. She did not have fever and her physical examination, including the neurologic system, was normal. Computerized tomography revealed an approximately 1 cm lesion compatible with subdural empyema and cerebral abscess in the right frontoparietal area in supratentorial sections. The patient was operated for wound revision and moxifloxacin was initiated. Since the operation materials revealed MRSA growth, vancomycin (4 x 500 mg, IV) was added to the treatment. The isolate was identified by conventional methods, and antibiotic susceptibility test performed by disk diffusion method showed that it was susceptible to levofloxacin, linezolid, rifampin, vancomycin and teicoplanin. Since no clinical response was obtained in two weeks, moxifloxacin was switched to rifampin (300 mg 1 x 2). On the 10th day of vancomycin + rifampin therapy, radiological findings showed development of cerebritis and therefore vancomycin was changed with linezolid (2 x 600 mg, IV). The control CT of the patient revealed regression of the brain lesion and linezolid + rifampin treatment continued for six weeks. The patient did not develop any hematological, liver or renal toxicity during the therapy and the radiological findings regressed. No relapse were detected in the one year follow-up period. This case suggested that linezolid might be a treatment alternative in the therapy of vancomycin-refractory MRSA brain abscess.

Deep brain stimulation for Holmes' tremor related to a thalamic abscess.

BACKGROUND: Medical treatment is usually ineffective for Holmes' tremor, and surgery is the treatment of choice for many patients. Here we report the case of a 14-year-old girl who developed Holmes' tremor related to a thalamic abscess and was successfully treated with thalamic deep brain stimulation. CASE REPORT: The patient presented with left hemiparesis and headache and was hospitalized. Investigation revealed a thalamic abscess in the left cerebral hemisphere. The abscess was drained via stereotactic surgery and a course of antibiotic treatment was completed. Four months after treatment, the patient developed Holmes' tremor in her left upper extremity. When attempts at medical treatment with levodopa, clonazepam, and trihexyphenidyl all failed, an implant was placed and deep brain stimulation of the ventral intermediate nucleus of the thalamus was initiated. During 2.5 years of follow-up, her tremor diminished by 90%. CONCLUSION: This case demonstrates that medically resistant Holmes' tremor related to a thalamic lesion can be successfully treated with thalamic deep brain stimulation.

Intracranial Nocardia recurrence during fluorinated quinolones therapy.

Nocardia infection is a well-recognized complication in renal transplant recipients and other immunocompromised hosts. It is mostly a primary pulmonary infection, which can disseminate to other organs in half of the cases. Nocardiosis is a life-threatening infection. Therefore, an efficient long-lasting treatment must be rapidly administered. We report 1 case of disseminated nocardiosis with pulmonary involvement, brain lesions, and bone lesions in a renal transplant patient, who was treated with stereotactic aspiration in association with high dose of trimethoprim/sulfamethoxazole (TMP/SMX) and imipenem, changed, after 3 weeks to moxifloxacin. First, clinical manifestations decreased after surgical drainage and combination therapy with the 2 antimicrobial agents, but later the patient developed a recurrence of brain lesions during treatment with quinolones. Consequently, the patient was again treated with TMP/SMX and imipenem, after which the patient recovered. It is surprising that moxifloxacin was efficient in vitro and the antimicrobial concentration in the central nervous system was high, yet the nocardial abscess recurred under this therapy.

Linezolid in the treatment of brain abscess due to Peptostreptococcus.

Brain abscesses can be caused by bacteria, fungi, and parasites. Among bacteria, anaerobic organisms include the Bacteroides species group, Fusobacterium, Peptostreptococcus, and Propionibacterium. In these cases, a 4-week course of parenteral penicillin/cefalosporin and metronidazole is the standard of treatment. We describe a case of brain abscess secondary to anaerobic infection with Peptostreptococcus, which was successfully treated with parenteral and oral linezolid after failure of standard therapy.

First successful treatment of Nocardia farcinica brain abscess with moxifloxacin.

Nocardia farcinica is an emerging pathogen in immunosuppressed patients causing both localized and disseminated infections. Many strains of this species are multidrug-resistant and require long-term antibiotic therapy, and consequently the choice of an oral treatment can be problematic. We report here the first case of successful treatment of N. farcinica brain abscess in a renal transplant recipient with an extended-spectrum fluoroquinolone, moxifloxacin.

[A case of multiple brain abscess effectively markedly responded to high dose panipenem/betamipron administration].

A 54-year-old, previously healthy female experienced headache, nausea and vomiting, and consulted our hospital regarding her symptoms. Her cerebrospinal fluid (CSF) showed leukocytosis with polymorphonucleosis and hypoglycemia, thus she was diagnosed with bacterial. She admitted to our hospital and combination therapy of ampicillin and cefotaxime was started. CSF and blood cultures was negative. On the third hospital day, despite a decrease in her CSF cell count, her consciousness level decreased and neck stiffness worsened. On the seventh hospital day, the CSF cell count increased again, and we changed antibiotics to panipenem/betamipron (PAPM/BP) at 4 g/day. On the tenth hospital day, the CSF cell count decreased, but by the twelfth hospital day her consciousness had deteriorated to a drowsy state. Brain CT and MRI revealed multiple brain abscesses and hydrocephalus. We increased the dose of PAPM/BP up to 8 g/day, and her neurological, CSF and brain MRI findings subsequently improved. The patient was discharged from our hospital on the sixty-ninth hospital day. As the frequency of beta-lactamase-producing bacteria is currently increasing, carbapenems should be considered as first choice of antibiotics for the initial treatment of multiple brain abscess.

The efficacy of trovafloxacin versus ceftriaxone in the treatment of experimental brain abscess/cerebritis in the rat.

Current estimates of the mortality associated with brain abscesses range from 0-24%, with neurological sequellae in 30-55% of survivors. Although the incidence of brain abscess appears to be increasing, likely due to an increase in the population of immunosuppressed patients, the condition is still sufficiently uncommon to make human clinical trials of therapy problematic. An animal model to study the efficacy of new treatment regimens, specifically, new antimicrobial agents is therefore necessary. This study uses a well-defined experimental paradigm as an inexpensive method of inducing and studying the efficacy of antibiotics in brain abscess. The rat model of brain abscess/cerebritis developed at this institution was used to determine the relative efficacy of trovafloxacin as compared to ceftriaxone in animals infected with Staphylococcus aureus. S. aureus ( approximately 10(5) CFU in 1 microliter) was injected with a Hamilton syringe, very slowly, over the course of 70 minutes after a two mm burr hole was created with a spherical carbide drill just posterior to the coronal suture and four mm lateral to the midline. Eighteen hours later treatment was begun; every 8 hours the rats were dosed with subcutaneous ceftriaxone (n = 10), trovafloxacin (n = 11) or 0.9% sterile pyogen-free saline (n = 10). After four days of treatment the brains were removed and sectioned with a scalpel. The entire injected hemisphere was homogenized and quantitative cultures performed. The mean +/- SEM log(10) colony forming units/ml S. aureus recovered from homogenized brain were as follows: controls 6.10 +/- 0.28; ceftriaxone 3.43 +/- 0.33; trovafloxacin 3.65 +/- 0.3. There was no significant difference in bacterial clearance between ceftriaxone versus trovafloxacin (p = 0.39). Trovafloxacin or other quinolones may provide a viable alternative to intravenous antibiotics in patients with brain abscess/cerebritis.

Breakthrough Scedosporium apiospermum (Pseudallescheria boydii) brain abscess during therapy for invasive pulmonary aspergillosis following high-risk allogeneic hematopoietic stem cell transplantation. Scedosporiasis and recent advances in antifungal therapy.

Systemic scedosporiasis due to the anamorph or asexual form Scedosporium apiospermum (Pseudallescheria boydii) has become an important cause of opportunistic mycosis, especially in patients undergoing high-risk hematopoietic stem cell transplantation. We report a case of rapidly progressive cerebellar hyalohyphomycosis due to Scedosporium apiospermum in an allogeneic marrow graft recipient receiving treatment for severe graft-versus-host disease. This fatal breakthrough intracranial abscess, due to amphotericin B-resistant (minimum inhibitory concentration > 16 micro g/ml) mold, developed during the course of systemic antifungal therapy given for multicentric pulmonary aspergillosis. Despite treatment with high-dose Abelcet (10 mg/kg daily), free amphotericin B was not detected in postmortem cerebellar tissue. A broad-spectrum triazole-based agent (voriconazole/UK-109, 496--Vfend), and a novel fungal cell wall inhibitor, an echinocandin/pneumocandin analog (caspofungin/MK-0991--Cancidas), which exhibit excellent in vitro activity against most clinical Pseudallescheria boydii-Scedosporium apiospermum isolates, have recently become available in the United States and may provide much needed treatment options for patients at risk.

Management of brain abscesses with sequential intravenous/oral antibiotic therapy.

Eight patients with brain abscesses who refused prolonged hospitalisation were treated with a short course (6-12 days) of intravenous antibiotics followed by prolonged treatment (15-19 weeks) with an oral antibiotic regimen consisting of metronidazole, ciprofloxacin and amoxicillin. All patients responded favourably as shown clinically and in imaging studies. No severe adverse events or sequelae were noted. On admission all patients had a normal or mildly impaired mental status, abscesses less than 3 cm in diameter and no serious predisposing factors. Although combined surgical/medical treatment remains the standard approach in management of these patients, the findings suggest that oral antibiotic therapy only subsequent to a short course of intravenous antibiotics may be an acceptable alternative in selected cases.

Salmonella meningitis and multiple cerebral abscesses in an infant.

The history of a 4-week-old infant with meningitis and multiple cerebral abscesses caused by Salmonella enteritidis is reported. Management included successful treatment with a prolonged course of antibiotics, including ciprofloxacin, neurosurgical drainage and long-term immunoglobulin supplements. No adverse effects of joint toxicity were detected.

[A patient with Streptococcus intermedius brain abscess treated with high dose penicillin G--susceptibility of the isolate to penicillin G and the concentration of penicillin G in cerebrospinal fluid].

We report here a 2-year-old boy with a Streptococcus intermedius brain abscess and bilateral ventriculitis successfully treated with a high dose penicillin G (200,000 U/kg/dose, 6 times a day, 1 hour continuous infusion). Although hydrocephalus residuced, the high dose penicillin G therapy cured his brain abscess and bilateral ventriculitis. The minimal inhibitory concentration of penicillin G to the isolate was 0.008 microgram/ml. The penicillin G concentration in the cerebrospinal fluid after 2 hours from the infusion was about 5 micrograms/ml. S. intermedius must be considered as one of the causative agents for brain abscess. High dose penicillin G therapy is one choice of treatment for brain abscess due to penicillin-susceptible streptococci.