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.

Higher incidence of prescribing rates and utilization of broad spectrum cephalosporin in young patients: A retrospective observational study in a tertiary care hospital.

Frequent use of antibiotics has been developed resistance and the use of broad spectrum cephalosporin must be limited in children. The study evaluated the association of prescribing patterns of third generation cephalosporin with diagnosis, age, availability of cultural sensitivity report and gender. It is an observational study that was carried out in the duration of six months in a low socio-economic tertiary care hospital. The data of six hundred and eighty-five (685) patients were collected from the medical records of the tertiary hospital. The cephalosporin are the most prescribed antibiotics in children 118/217 (54.3%) followed by adults 119/403 (29.5%) and teenagers 18/65 (27.6%). Whereas, 75/217 (34.5%), 126/403 (31.2%) and 22/65 (33.8%) were prescribed cephalosporin with combination in patients respectively. The culture sensitivity was performed only in 25% of patients i.e., 173/685, Of 173 culture reports 70 and 91 cases from children and adults respectively. Blood is mostly examined specimen in children and urine in adults. Escherichia coli was highly recovered pathogen in culture sensitivity report. The study concluded broad spectrum cephalosporin antibiotics were highly prescribed in children. The culture sensitivity was performed in limited number of patients. Antibiotics stewardship programme will be implemented to reduce the prescribing of broad spectrum cephalosporin in young patients.

High-Dosage Cefazolin Achieves Sufficient Cerebrospinal Diffusion To Treat an External Ventricular Drainage-Related Staphylococcus aureus Ventriculitis.

A patient received continuous infusion of cefazolin 10 g then 8 g daily for an external ventricular drainage-related methicillin-susceptible Staphylococcus aureus (MSSA) ventriculitis. Median free concentrations in the cerebrospinal fluid were 11.9 and 6.1 mg/liter after 10- and 8-g doses, respectively. Free concentrations in the cerebrospinal fluid were always above the MIC usually displayed by methicillin-susceptible Staphylococcus aureus (MSSA) isolates. These results support the use of high-dose cefazolin to achieve sufficient meningeal concentrations.

Tigecycline in the treatment of multidrug-resistant Acinetobacter baumannii meningitis: Results of the Ege study.

OBJECTIVES: In this study we retrospectively reviewed A. baumannii meningitis cases treated with tigecycline including regimens and evaluated the efficacy of tigecycline in the therapy. PATIENTS AND METHODS: Study was performed in seven tertiary-care educational hospitals from five cities of Turkey and one center from France. We extracted data and outcomes of all adult (aged >18) patients with culture proven A. baumannii meningitis treated with tigecycline including antibiotic therapy until April 2016. RESULTS: A total of 23 patients (15 male and eight female) fulfilled our inclusion criteria. All Acinetobacter strains were carbapenem-resistant and susceptible to tigecycline. Six cases received tigecycline monotherapy while 17 received tigecycline including combination therapy (10 with colistin, 4 with netilmicin, 3 with amikacin, 4 with meropenem). Seven of 23 cases (30%) died during the tigecycline including therapy (1 in monotherapy, 4 in colistin, 2 in netilmicin, 1 amikacin, one case received tigecycline + netilmicin followed by tigecycline + colistin). Hence, overall end of treatment (EOT) success was 70%. However, since further 27% died due to additional nosocomial infections, overall clinical success (relieved symptoms at the EOT and one-month post-therapy survival without any relapse or reinfection) decreased to 43%. CONCLUSION: We conclude that tigecycline may be an alternative in the salvage treatment of nosocomial multidrug-resistant Acinetobacter spp. meningitis. Acinetobacter spp. Meningitis.

Voriconazole Treatment for an Infant With Intractable Candida glabrata Meningitis.

We report voriconazole levels in an infant with disseminated Candida glabrata infection who received combination antifungal therapy and rescue voriconazole treatment. Serum and cerebrospinal fluid voriconazole levels were higher than anticipated and above target. Dose reduction did not lead to a reduction in the blood or cerebrospinal fluid levels. The patient did not exhibit identifiable drug toxicity.

Coccidioidal Meningitis: A Review on Diagnosis, Treatment, and Management of Complications.

PURPOSE OF REVIEW: This article summarizes the diagnosis and treatment of coccidioidal meningitis (CM) and its complications. An overview of current and prospective pharmacologic treatment options and monitoring parameters is provided. A consensus has not been reached regarding universally accepted therapeutic serum levels for azoles because of insufficient evidence. We describe the preferred therapeutic drug level ranges that our institution uses to monitor azole therapy. RECENT FINDINGS: Ho et al. described the preparation and administration of intrathecally delivered amphotericin B deoxycholate. Thompson et al. described possible benefits of controversial adjuvant corticosteroid therapy for secondary prevention of vasculitic infarction secondary to CM. CM was universally fatal until the advent of intrathecal amphotericin B deoxycholate therapy, the introduction of which changed the natural history of the disease in much the same way as penicillin changed the natural history of bacterial meningitis. Although there was still significant morbidity, survival rates drastically increased to approximately 70%. The introduction of azole therapy has decreased the side effects and burden of treatment but without a significant change in CM-related mortality and morbidity compared with the use of intrathecal amphotericin B deoxycholate therapy.

Successful treatment of postoperative multidrug-resistant Acinetobacter baumannii meningitis by tigecycline.

Tigecycline is a broad-spectrum antibiotic with activity against multidrug-resistant (MDR) bacteria. It has limited indications. Studies are necessary to elaborate new guidelines. Here we report a case of postoperative MDR Acinetobacter baumannii meningitis treated by tigecycline combined with colimycin for 21 days. The treatment was well tolerated with a favourable outcome. In conclusion, tigecycline was shown to be effective in a case of MDR A. baumannii meningitis.

Safety and Efficacy of Liposomal Cytarabine in the Treatment of Neoplastic Meningitis.

OBJECTIVES: Although rare, neoplastic meningitis (NM) has been increasingly observed in patients with cancer due to the prolonged course of the disease. Intrathecal chemotherapy with methotrexate or cytarabine with repeating injection schedules of 2-3 times per week is currently the mainstay of treatment. An efficacious and comfortable treatment alternative might be represented by liposomal cytarabine. METHODS: In this retrospective study, we reviewed all patients with NM due to solid tumors or hematological malignancies treated with liposomal cytarabine at our institution between March 2004 and September 2011. The primary endpoint was treatment response, which was defined as improvement in neurological symptoms and/or conversion of the initial cerebrospinal fluid cytology and/or response in the radiological findings. The main secondary endpoint was safety. RESULTS: Fifty-one adult patients were evaluable for safety and 44 patients for efficacy. In 36 patients (81.8%), a treatment response was achieved. The median overall survival after diagnosis of NM was 11 months (95% confidence interval 8.8-13.2). Adverse events grade 1-4 occurred in 31 patients (60.8%), whereas grade 3-4 occurred in 18 patients (35.3%). CONCLUSION: The encouraging efficacy and safety data obtained in our analysis and the convenient administration schedule make intrathecal liposomal cytarabine a favorable treatment option for NM patients.

Daptomycin plus trimethoprim/sulfamethoxazole combination therapy in post-neurosurgical meningitis caused by linezolid-resistant Staphylococcus epidermidis.

Post-neurosurgical infection is a serious complication that occurs in approx. 4% of all patients undergoing neurosurgical procedures and is associated with high morbidity and mortality rates and prolonged length of intensive care unit (ICU) stay. Coagulase-negative staphylococci (CoNS), especially methicillin-resistant Staphylococcus epidermidis (MRSE), are the most frequent pathogens involved in CNS post-neurosurgical meningitis. Treatment is challenging especially in patients with meningitis due to multidrug- resistant (MDR) CONS. Herein, we report a unique case of post-neurosurgical meningitis due to MRSE resistant to linezolid (a molecular analysis revealed the presence of the mutation G2576T on domain V of the 23S rRNA gene) and with reduced susceptibility to glycopeptides, successfully treated with a combination of daptomycin at 10 mg/kg daily plus trimethoprim/sulfamethoxazole (TMP/SMX). This antibiotic combination showed an indifferent interaction in in vitro studies. Daptomycin serum and cerebrospinal fluid (CSF) concentrations, determined through blood and CSF samples drawn just prior to and 4 h after the third dose, were 18.9-0.78 and 51.65-3.1 mg/L, respectively. These values allowed us to approximate a 5-6% penetration rate of the drug through an inflamed blood-brain barrier. In conclusion, although further studies are needed, combination of high-dose daptomycin plus TMP/SMX is a reasonable option for treatment of meningitis caused by multidrug-resistant S. epidermidis.

Pharmacotherapy for pneumococcal infections: an update.

INTRODUCTION: The management of pneumococcal diseases still places a significant burden on medical and economic resources. The subjects at greatest risk of pneumococcal infections are children. AREAS COVERED: The aim of this review is to analyse the best current therapeutic approach to pneumococcal resistance, taking into account the level of susceptibility of Streptococcus pneumoniae, and the pharmacokinetics and pharmacodynamics of different antibiotics in the various pneumococcal diseases. EXPERT OPINION: Antibiotic treatment of a number of pneumococcal diseases remains difficult or impossible due to the presence of strains resistant to commonly used antibiotics. In children the problem is significantly more important than in adults due to the reduced number of licenced drugs for subjects in the first years of life. The new conjugate pneumococcal vaccines containing 10 (PCV10) and 13 serotypes (PCV13), which include most of the recently emerging strains, might reduce the incidence of pneumococcal infections and the circulation of resistant pathogens. However, it is likely that optimal results will only be reached after the development of effective vaccines based on conserved proteins that are capable of preventing all pneumococcal infections, regardless of the serotype of the causative organism.

Curcumin alleviates eosinophilic meningitis through reduction of eosinophil count following albendazole treatment against Angiostrongylus cantonensis in mice.

Angiostrongylus cantonensis (A. cantonensis) is the most common cause of parasitic eosinophilic meningitis worldwide. By using an animal model of BALB/c mice infected with A. cantonensis, previous studies indicated that the anthelmintic drug, albendazole, could kill A. cantonensis larvae and prevent further infection. However, the dead larvae will induce severe immune responses targeting at brain tissues. To alleviate the detrimental effects caused by the dead larvae, we administered curcumin, a traditional anti-inflammatory agent, as a complementary treatment in addition to albendazole therapy, to determine whether curcumin could be beneficial for treatment. The results showed that although curcumin treatment alone did not reduce worm number, combined treatment by albendazole and curcumin helped to reduce eosinophil count in the cerebrospinal fluid, better than using albendazole alone. This alleviating effect did not affect albendazole treatment alone, since histological analysis showed similar worm eradication with or without addition of curcumin. Nevertheless, curcumin treatment alone and combined albendazole-curcumin treatment did not inhibit MMP-9 expression in the brain tissue. In conclusion, curcumin, when used as a complementary treatment to albendazole, could help to alleviate eosinophilic meningitis through suppression of eosinophil count in the cerebrospinal fluid.

Evaluation of anti-migraine potential of Areca catechu to prevent nitroglycerin-induced delayed inflammation in rat meninges: possible involvement of NOS inhibition.

ETHNOPHARMACOLOGICAL RELEVANCE: Areca catechu nut extract is a popular folk remedy for the treatment of migraine in Kerala and Tamil Nadu states of India. AIM OF THE STUDY: In order to prove the claimed utilization of plant, the effect of hydroalcoholic extract of Areca catechu nut (ANE) was investigated in nitroglycerine induced inflammation in rat meninges. In these models infusion of nitric oxide donor glyceryl trinitrate (GTN) produces augmented plasma protein extravasation (PPE) in dura mater, provides an important substrate for the development of migraine in rats. MATERIALS AND METHODS: The effect on plasma protein extravasation was assessed in both the models of intravenous and topical GTN application following oral administration of ANE (250 mg/kg and 500 mg/kg) in both curative and preventive treatment and compared with that of control positive. The l-NAME (15 mg/kg, i.v.) was used as reference standard. Plasma protein extravasation was measured using fluorescein as marker and was measured using a Perkin-Elmer LS-30 luminescence spectrometer. RESULTS: Expression of iNOS in the spleen after intravenous injection produced PPE into the dura mater in control positive group was significantly (P<0.01) reduced to 1.553±0.02499 and 1.398±0.01887 by preventive treatment with ANE at the dose of 250 and 500 mg/kg, orally, respectively. The extravasation produced by topical GTN due to expression of iNOS in dural macrophages was also reduced to 1.555±0.03384 and 1.425±0.01204 by preventive treatment with ANE at the dose of 250 and 500 mg/kg, orally, respectively. While ANE do not showed any significant results in curative treatment in both the models of i.v. and topical GTN application. CONCLUSION: These findings collectively indicate that the extract exhibited significant inhibition of iNOS, which may be the probable mechanism for its anti-migraine activity, providing evidence, at least in part, for its folkloric use.

Efficacy of combined treatment with albendazole and baicalein against eosinophilic meningitis induced by Angiostrongylus cantonensis in mice.

Angiostrongylus cantonensis infection causes eosinophilic meningitis in humans. Baicalein is a flavonoid originally isolated from the roots of Scutellaria baicalensis Georgi. In this study we evaluated the efficacy of the combination of albendazole and baicalein for treating eosinophilic meningitis in BALB/c mice. Therapeutic efficacy included the survival time, body weight, neurological function, leucocyte and eosinophil counts, eotaxin concentration, matrix metalloproteinase-9 (MMP-9) activity, larval recovery and histopathological examination. The results showed that the combination of albendazole and baicalein was more effective than either drug administered singly. Combination therapy increased the survival time, decreased body weight loss, neurological dysfunction, leucocyte response, eotaxin concentration and MMP-9 activity. Our results suggest that the combination of albendazole and baicalein may exhibit synergistic beneficial effects in the treatment of eosinophilic meningitis induced by A. cantonensis.

Efficacy of curcumin therapy against Angiostrongylus cantonensis-induced eosinophilic meningitis.

Angiostrongylus cantonensis can invade the central nervous system, leading to human eosinophilic meningitis or eosinophilic meningoencephalitis. Curcumin is a natural product which has the effects of anti-inflammation, anti-oxidation and anti-carcinogensis, while the administration of curcumin has been reported to possibly relieve the symptoms of meningitis. The present study tested the potential efficacy of curcumin in A. cantonensis-induced eosinophilic meningitis of BALB/c mice. Assay indicators for the therapeutic effect included the larvicidal effect, eosinophil counts and matrix metalloproteinase-9 (MMP-9) activity in angiostrongyliasis. Eosinophils were mildly reduced in treatment groups compared with infected-untreated mice. However, there were no significant differences in larvicidal effects or MMP-9 activity. This study suggests that anti-inflammatory treatment with curcumin alone has low efficacy, but the treatment does not interfere with MMP-9 expression and is not useful for larvicidal effects. The possible reasons include low curcumin across the blood-brain barrier and also those larvae that survive stimulate MMP-9 production, which promotes blood-brain barrier damage, with leukocytes then crossing the blood-brain barrier to cause meningitis. Further studies will be required to test these possibilities.

Angiostrongylus cantonensis: apoptosis of inflammatory cells induced by treatment with mebendazole or/and interleukin 12 in mice.

Angiostrongylus cantonensis is the major cause of human eosinophilic meningoencephalitis. ICR mice were infected orally with 35 infective larvae and sacrificed at 4-14 days, 25 days or 32 days post infection (dpi) for pathological and immunocytochemical examinations. In the non-treated group, no apoptosis signal was found in the meninges or parenchyma of the brains (4-14 dpi). Only a few apoptotic cells were noticed at 25 dpi (3%) and 32 dpi (10%). In the groups, the animals were given a single dose of mebendazole (20 mg/kg, per os at various times) or injections of interleukin 12 (IL-12) (10 ng/daily, intraperitoneally), all the animals were sacrificed at 14 dpi; the number of apoptotic cells was increased (17-21%). In the group that received a single dose of mebendazole (4 dpi) in combination with IL-12 injections (4-13 dpi), mild meningitis was observed, and most of the infiltrated inflammatory cells were in the apoptotic program (55%). Taken together, apoptosis of the inflammatory cells (most were eosinophils) could be induced when the infected mice were treated with mebendazole or/and IL-12.

Chinese herbal medicine Yin-Chen-Extract as an adjunct to anthelmintic albendazole used against Angiostrongylus cantonensis-induced eosinophilic meningitis or meningoencephalitis.

The effects of albendazole and Yin-Chen-Extract co-therapy on Angiostrongylus cantonensis-induced eosinophilic meningitis in BALB/c mice were evaluated. Assay indicators for the therapeutic effect include worm recovery, histopathological score of the fourth ventricle, tissue-type plasminogen activator, urokinase-type plasminogen activator, matrix metalloproteinase-9, cerebrospinal fluid total protein, leukocyte counts, and proinflammatory cytokines. As a result, albendazole and Yin-Chen-Extract co-therapy significantly decreased (P < 0.05) these factors. Although Yin-Chen-Extract may possess pharmacologic activities beneficial to the inhibition of parasite-induced inflammation, many of these hypothetical benefits await scientific testing and confirmation before application. This study suggests that the combination of Yin-Chen-Extract and albendazole has synergistic effects in managing eosinophilic meningitis or eosinophilic meningoencephalitis.

Aeromonas meningitis complicating medicinal leech therapy.

Medicinal leeches have an important and expanding role in medicine, but infection can complicate their use. We describe a unique case of Aeromonas meningitis associated with the use of leech therapy to salvage a skin flap after central nervous system surgery.

Vancomycin acts synergistically with gentamicin against penicillin-resistant pneumococci by increasing the intracellular penetration of gentamicin.

Vancomycin and gentamicin act synergistically against penicillin-resistant pneumococci in vitro and in experimental rabbit meningitis. The aim of the present study was to investigate the underlying mechanism of this synergism. The intracellular concentration of gentamicin was measured by using the following experimental setting. Bacterial cultures were incubated with either gentamicin alone or gentamicin plus vancomycin for a short period (15 min). The gentamicin concentration was determined before and after grinding of the cultures by using the COBAS INTEGRA fluorescence polarization system (Roche). The grinding efficacies ranged between 44 and 54%, as determined by viable cell counts. In the combination regimen the intracellular concentration of gentamicin increased to 186% compared to that achieved with gentamicin monotherapy. These data suggest that the synergy observed in vivo and in vitro is based on an increased intracellular penetration of the aminoglycoside, probably due to the effect of vancomycin on the permeability of the cell wall.