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Primary fungal infection of the central nervous system (CNS) is rare but often associated with severe prognosis. Diagnosis is complicated since cerebrospinal fluid (CSF) samples obtained from lumbar puncture usually remain sterile. Testing for fungal antigens in CSF could be a complementary diagnostic tool. We conducted such measurements in CSF from patients with CNS fungal infection and now discuss the usefulness of ventricular puncture. Mannan and (1→3)ß-D-glucan (BDG) testing were retrospectively performed in CSF samples from three patients with proven chronic CNS fungal infection (excluding Cryptococcus), and subsequently compared to 16 controls. Results from lumbar punctures and those from cerebral ventricles were confronted. BDG detection was positive in all the CSF samples (from lumbar and/or ventricular puncture) from the three confirmed cases. In case of Candida infection, mannan antigen measurement was positive in 75% of the CSF samples. In the control group, all antigen detections were negative (n = 15), except for one false positive. Faced with suspected chronic CNS fungal infection, measurement of BDG levels appears to be a complementary diagnostic tool to circumvent the limitations of mycological cultures from lumbar punctures. In the event of negative results, more invasive procedures should be considered, such as ventricular puncture.

Blastomycosis is a local or systemic infection, caused by Blastomyces dermatitidis (B. dermatitidis) or B. gilchristii. Blastomycosis has been described as “the great pretender,” alluding to the fact that it manifests in a wide range of symptoms and disease severity. Central nervous system (CNS) involvement, although rare, carries significant mortality. Due to the limited published reports of CNS blastomycosis, we present an updated cohort with eight cases of proven or probable CNS blastomycosis describing presentation, diagnosis, treatment and outcomes. Headache was the most common presenting symptom. Magnetic resonance imaging (MRI) proved to be the superior imaging study. All patients in our cohort were diagnosed by histopathological staining or cultures of tissue or fluid obtained from CNS or extra-CNS lesions. All patients that received treatment with Liposomal amphrotericin B for at least 10 days followed by a prolonged azole therapy did not have relapse. Two patients with late diagnoses died during hospitalization. Our findings confirm the importance of timely diagnosis and treatment of CNS blastomycosis to improve outcomes especially with an azole that have a high CNS penetration and a good intrinsic activity for B. dermatitidis such as voriconazole.

Hormographiella is a rare fungal pathogen in humans; however, case reports have described disseminated infection in immunocompromised hosts. This pathogen has been described to yield poor prognosis in patients who harbor it. Herein, we present a case report of autopsy-proven disseminated Hormographiella aspergillata infection, confirmed by DNA sequencing, in a patient experiencing a relapse of leukemia.This 54-year-old Caucasian man with chronic myelogenous leukemia (CML) that had been diagnosed in 1989, after having received a hematopoietic cell allotransplant from a compatible sibling donor, had B-cell lymphoid-blast phase of CML in April of 2013, with multiple relapses. His most recent relapse was in September of 2016, when bone marrow biopsy showed 90% blasts. The results of bronchoalveolar lavage (BAL) cultures were positive for filamentous fungus infection. The patient developed encephalopathy and worsening respiratory statusand tachycardia with flutter and hypotension, which resulted in his death.At autopsy, bilateral pleural effusions, multiple right pleural nodules, and subarachnoid hemorrhage were noted. Angioinvasive hyphal fungi were found in the right frontal lobe of the brain and the right upper lobe of the lung. Morphologically, the fungi had multiseptate, branching hyphae. The bronchoalveolar lavage specimen grew a fungus for which the colony morphologic characteristics and microscopic features were compatible with a Hormographiella species. H. aspergillata from the bronchoalveolar lavage was further identified by sequencing the D2 hypervariable region of the large-subunit (LSU) ribosomal DNA gene and the full internal transcribed spacer (ITS) regions.

Background. Fungal infections of the central nervous system (FICNS) are important causes of morbidity and mortalityamong immunocompromised pediatric patients. Standard diagnostic modalities lack the sensitivity for detecting and therapeutically monitoring these life-threatening diseases. Current molecular methods remain investigational. (1!3)-β-D-glucan (BDG) is a cell wall component found in several fungal pathogens, including Candida and Aspergillus spp. Detecting BDG in cerebrospinal fluid (CSF) may be an important approach for detecting and therapeutically monitoring FICNS. To date, there has been no study that has investigated the effectiveness of CSF BDG as a diagnostic and therapeutic marker of FICNS in children. Methods. Serial BDG levels were measured in serum and CSF samples obtained from pediatric patients (aged 0–18 years) with a diagnosis of probable or proven Candida or Aspergillus CNS infection. Results. Nine cases of FICNS were identified in patients aged 1 month to 18 years. Two patients were infected with an Aspergillus species, and 7 patients were infected with a Candida species. All the patients at baseline had detectable BDG in their CSF. Among 7 patients who completed therapy for an FICNS, all elevated CSF BDG levels decreased to

Background Late-onset sepsis (LOS) is an important cause of morbidity and mortality in very low birth weight (VLBW) infants. Aim To determine the incidence, risk factors and etiology of LOS. Methods LOS was investigated in a multicenter prospective cohort of infants at eight public university neonatal intensive care units (NICUs). Inclusion criteria included inborn, 23-33 weeks of gestational age, 400-1499 g birth weight, who survived >3 days. Results Of 1507 infants, 357 (24%) had proven LOS and 345 (23%) had clinical LOS. Infants with LOS were more likely to die. The majority of infections (76%) were caused by Gram-positive organisms. Independent risk factors for proven LOS were use of central venous catheter and mechanical ventilation, age at the first feeding and number of days on parenteral nutrition and on mechanical ventilation. Conclusion LOS incidence and mortality are high in Brazilian VLBW infants. Most risk factors are associated with routine practices at NICU.

We demonstrate autosomal-recessive Caspase Recruitment Domain-containing protein 9 (CARD9) deficiency in a patient with relapsing C. albicans meningoencephalitis. We identified a novel, hypomorphic mutation with intact Th17 responses, but impaired GM-CSF responses. We report complete clinical remission with adjunctive GM-CSF therapy, suggesting that a CARD9/GM-CSF axis contributes to susceptibility to candidiasis.

Six cases of Rhinocladiella mackenziei cerebral phaeohyphomycosis are being reported for the first time in Pakistan. Identification was confirmed by DNA sequencing (isolates and fixed tissue). Diabetes, head trauma, immunosuppressive treatment, and postpartum state were present in 4 cases. Two survivals and 3 fatalities occurred, with 1 patient lost to follow-up.

Penicillium marneffei is an important human immunodeficiency virus-associated opportunistic infection endemic in Southeast Asia. Central nervous system infection has not been described. We report the first case series of 21 human immunodeficiency virus-infected patients who presented with a syndrome consistent with acute central nervous system infection and who had Penicillium marneffei isolated from cerebrospinal fluid.

Clinical manifestations, treatment, and outcomes of cutaneous cryptococcosis in solid organ transplant (SOT) recipients are not fully defined. In a prospective cohort comprising 146 SOT recipients with cryptococcosis, we describe the presentation, antifungal therapy, and outcome of cutaneous cryptococcal disease. Cutaneous cryptococcosis was documented in 26/146 (17.8%) of the patients and manifested as nodular/mass (34.8%), maculopapule (30.4%), ulcer/pustule/abscess (30.4%), and cellulitis (30.4%) with 65.2% of the skin lesions occurred in the lower extremities. Localized disease developed in 30.8% (8/26), and disseminated disease in 69.2% (18/26) with involvement of the central nervous system (88.9%, 16/18), lung (33.3%, 6/18), or fungemia (55.6%, 10/18). Fluconazole (37.5%) was employed most often for localized and lipid formulations of amphotericin B (61.1%) for disseminated disease. Overall mortality at 90 days was 15.4% (4/26) with 16.7% in disseminated and 12.5% in localized disease (P = 0.78). SOT recipients who died were more likely to have renal failure (75.0% vs. 13.6%, P = 0.028), longer time to onset of disease after transplantation (87.5 vs. 22.6 months, P = 0.023), and abnormal mental status (75% vs. 13.6%, P = 0.028) than those who survived. Cutaneous cryptococcosis represents disseminated disease in most SOT recipients and preferentially involves the extremities. Outcomes with appropriate management were comparable between SOT recipients with localized and disseminated cryptococcosis.

Background Central nervous system (CNS) involvement with Blastomyces dermatitidis is an uncommon and potentially fatal complication of blastomycosis. Methods We retrospectively reviewed 22 patients with CNS blastomycosis at our institutions from 1990 through 2008 (13 proven, 5 probable, and 4 possible cases). Results Magnetic resonance imaging was used in most patients, alone or in addition to computed tomography. CNS blastomycosis manifested as epidural abscess (1 of 22), meningitis (7 of 22), intracranial mass lesions (10 of 22), and concomitant intracranial mass lesions and meningitis (4 of 22). All patients received amphotericin B deoxycholate or a lipid formulation of amphotericin B as part of their treatment regimens. Most patients received amphotericin B followed by a prolonged course of oral azole therapy (voriconazole, fluconazole, or itraconazole). Four (18%) of 22 patients died during follow-up. Conclusions On the basis of these data, we recommend initial treatment with a lipid formulation of amphotericin B followed by a prolonged course of oral azole therapy, preferably voriconazole.

Objectives: We studied the efficacy of voriconazole compared with amphotericin B in a murine model of central nervous system infection by Cryptococcus neoformans. Infection was established intracerebrally. Methods: Mice were treated with voriconazole at 10, 40 or 60 mg/kg/day orally or with amphotericin B at 1.5 mg/kg/day intraperitoneally. Treatment began 1 day after infection and continued for 10 days post-infection. Tissue burden studies were performed on day 7 and 1 day after the treatment finished. Results: Both drugs were able to significantly prolong survival with respect to the control group. The highest tissue burden reduction was achieved with voriconazole at 60 mg/kg/day. Conclusions: We have developed a murine model of cryptococcal central nervous system infection and demonstrated that voriconazole has a potential for the treatment of cryptococcosis.

The epidemiological, clinical and laboratory features of 13 cases of neuroparacoccidioidomycosis (NPCM) were analysed. All patients were men, with a mean age of 41.6 years. The lungs were involved in 11 cases (84.6%) and only two cases had mycosis limited to the central nervous system. Co-morbidity was observed in four patients (malignant neoplasm in three and diabetes mellitus in one). The most frequent neurological manifestations were paresis (eight cases), headache (five cases) and gait disturbance (four cases). Neuroimaging diagnosis showed a predominance of multiple round lesions with ring enhancement following contrast medium injection. Lesions were seen in the brain hemispheres (nine cases), thalamus (nine cases), cerebellum (four cases), brainstem (four cases) and spinal cord (four cases). Most cases responded well to therapy. Lesions with enhancement following contrast medium injection persisted in four patients for a period of 6 months to 8 years. These findings emphasize the importance of considering NPCM in the differential diagnosis of brain and spinal cord lesions in endemic areas of paracoccidioidomycosis.

Cerebral blastomycosis is a rarely reported disease. We report three cases of cerebral blastomycosis previously treated with standard antifungal therapy, which were subsequently successfully treated with voriconazole. The first is a 29-year-old man who initially presented with concomitant cutaneous and osseous blastomycosis; the second is a 50-year-old man who initially presented with prostatic, pulmonary and cutaneous lesions. The third patient was a 63-year-old man who presented with hemiplegia and multiple intra-cerebral blastomycomas. This report represents the first two documented relapses, in Canada, of CNS blastomycosis following treatment with itraconazole and, to our knowledge, among the first three worldwide human cases of cerebral blastomycosis treated successfully with voriconazole.

A multinational, multicentre, open-label clinical trial was conducted to evaluate the safety and efficacy of posaconazole, an extended-spectrum triazole antifungal agent, in subjects with invasive fungal infections who had refractory disease or who were intolerant of standard antifungal therapy. In this subanalysis, we report on those subjects in this trial who had a fungal infection that involved the CNS.Subjects received posaconazole oral suspension 800 mg/day in divided doses for up to 1 year; however, subjects could receive additional therapy as part of a treatment-use extension protocol. A blinded, third-party data review committee determined subject eligibility and outcome.Of the 330 subjects who enrolled in the study, 53 had infections of the CNS, of which 39 were considered evaluable for efficacy. Most had refractory disease (37 of 39) and underlying HIV infection (29 of 39). Twenty-nine subjects had cryptococcal infections, and 10 had infections caused by other fungal pathogens [Aspergillus spp. (four), Pseudallescheria boydii (two), Coccidioides immitis (one), Histoplasma capsulatum (one), Ramichloridium mackenziei (one), and Apophysomyces elegans plus a Basidiomycetes sp. (one)]. Successful outcomes were observed in 14 of 29 (48%) subjects with cryptococcal meningitis and five of 10 (50%) subjects with CNS infections due to other fungal pathogens. Posaconazole was well tolerated.These data suggest that posaconazole, as an oral medication, has clinical activity against fungal infections of the CNS and may provide a valuable alternative to parenteral therapy in patients failing existing antifungal agents.

Objectives: Currently, few options exist to treat central nervous system (CNS) aspergillosis, which is usually fatal. We tested the efficacy of Abelcet and caspofungin, alone and in combination for treatment of this disease. Methods: Male CD-1 mice were immunosuppressed with 200 mg/kg cyclophosphamide 2 days prior to infection and every 5 days thereafter. In the first study, mice were infected intracerebrally with 2.1 x 10 6 conidia/mouse of Aspergillus fumigatus; 10 days of once daily therapy began one day later. Groups of 10 received 0.8, 4, or 8 mg/kg of Abelcet, intravenously (iv), or caspofungin, intraperitoneally, 0.8 mg/kg of conventional amphotericin B (AmB) iv, or no treatment. In a second study, mice were challenged with 6.4 × 10 6 conidia and given no treatment, 8 mg/kg of Abelcet or caspofungin, alone or in combination. On day 14, cfu were determined in survivors by plating of organ homogenates. Results: In the first study, mice given any regimen of Abelcet or caspofungin had a survival rate ≥80% whereas untreated had 90% mortality. All drug regimens prolonged survival (P≤ 0.0008) and reduced cfu (P ≤ 0.0001-0.003) recovered from the brains and kidneys compared with untreated. Abelcet showed an apparent dose-related reduction of cfu in the brains. Abelcet at 4 or 8 mg/kg were equivalent to AmB in reducing cfu from both organs (P > 0.05); AmB was superior to 0.8 mg/kg of Abelcet in the brain only (P< 0.02). Abelcet at 8 mg/kg or AmB at 0.8 mg/kg were superior to all regimens of caspofungin in reducing cfu (P ≤ 0.05-0.001). In the second study, Abelcet alone significantly prolonged survival and reduced cfu in the organs versus the controls. Caspofungin did not significantly prolong survival or reduce cfu in comparison with the controls. In combination, Abelcet and caspofungin were equivalent to Abelcet alone. Conclusions: Abelcet proved to be efficacious, but not curative, in the treatment of CNS aspergillosis and was equivalent overall to conventional AmB. Caspofungin was not as effective against the larger inoculum, but did not enhance or interfere with the efficacy of Abelcet. Since Abelcet displayed dose-responsive efficacy, it is possible higher doses could produce superior results, yet not show toxicity.

Cryptococcosis is the third most common deep fungal infection in China and has not yet been reported to be associated with HIV infection there. We report the management of non-HIV-related cryptococcosis, including cutaneous cryptococcosis, pulmonary cryptococcosis and cryptococcal infection of central nervous system (CNS). Establishment of the diagnosis of cutaneous cryptococcosis and pulmonary cryptococcosis were mainly based on the histopathologic examination and mycologic culture, with CNS cryptococcal infection based on mycologic examination and latex agglutination test on cerebrospinal fluid. The treatment of cutaneous cryptococcosis included systemic administration of amphotericin B (AMB), 5-flucytosine and triazole agents such as fluconazole and itraconazole combined with topical ketoconazole cream. Treatment of pulmonary cryptococcosis included systemic use of antifungal medication combined with surgical removal of pulmonary lesions. The treatment of CNS cryptococcal infection was challenging. In this study, 53 patients with CNS cryptococcal infection were divided into three groups according to the antifungal regimens applied: eight patients (group I) received intravenous AMB alone or in combination with 5-flucytosine, five patients (group II) received intravenous fluconazole alone or with 5-flucytosine, and 40 patients (group III) received a two-phase therapy, active therapy and consolidation therapy. In active therapy, the patients received intrathecal and intravenous administration of AMB alone or with 5-flucytosine until the mycological culture of cerebrospinal fluid (CSF) became negative. Consolidation therapy followed active therapy by continuous use of oral fluconazole or itraconazole until direct microscopic examination of CSF was negative for three consecutive weeks. In group I, five patients were cured, two improved, one died and one had relapse. In group II, two patients were cured, one improved and two died. In group III, thirty-nine out of forty patients were cured without recurrence. These results indicate that the two-phase protocol was more desirable for the treatment of non-HIV associated cryptococcal infection of CNS.

Aim: To report presentation and outcome of rhino-orbital-cerebral mucormycosis (ROCM) exclusively in patients with diabetes mellitus. Methods: Retrospective, non-comparative, interventional analysis of the medical records of 35 patients with ROCM among 22 316 patients with diabetes seen over the last 12 years. Results: A cohort of 23 men and 12 women with a mean (SD) age of 47.3 (14.4) years (range 18–70 years) was studied. Five patients had type 1 diabetes mellitus, 29 had type 2 diabetes mellitus, and one had secondary diabetes. Nine patients had ROCM as the first clinical manifestation of diabetes. The mean (SD) blood glucose at presentation was 20.6 (8.3) mmol/l (range 10.0 to 53.3 mmol/l) and 17 patients had ketosis/ketoacidosis. Ophthalmic symptoms and signs were pronounced: external ophthalmoplegia (89%), proptosis (83%), visual loss (80%), chemosis (74%), and eye lid gangrene (14%). Non-ophthalmic manifestations included sinusitis (100%), nasal discharge/ulceration (74%), infranuclear VI nerve palsy (46%), palatal necrosis (29%), cerebral lobe involvement (20%), and hemiparesis (17%). Computed tomography/magnetic resonance imaging showed involvement of paranasal sinuses in all patients with ethmoid (86%) and maxillary (80%) sinuses being most frequently involved. Orbital involvement was observed in 80% of patients with cavernous sinus thrombosis in 11%, and internal carotid occlusion and hydrocephalus in 3% each. All were treated with amphotericin B (3–3.5 g) and 26 (74%) patients underwent appropriate surgery. Twenty one patients (68%) survived with a mean (SD) follow up of 39.6 (34.1) months (range 10 months to 11 years). Factors related to poor survival included delay in diagnosis and treatment (p Conclusions: In patients with diabetes and ROCM, ROCM was the presenting manifestation in one fourth of the patients. Ophthalmic and extensive cerebral involvement predominated in the clinical picture. Delay in treatment due to late presentation and associated complications were major determinants of the survival outcome in these patients.

Phaeohyphomycosis refers to infections caused by darkly pigmented fungi. These fungi rarely cause life-threatening disease. We reviewed 101 cases of culture-proven primary central nervous system phaeohyphomycosis reported in the English-language literature from 1966 to 2002. The most frequently isolated species was Cladophialophora bantiana. The next most frequent isolate was Ramichloridium mackenziei, seen exclusively in patients from the Middle East. More than one-half of the cases occurred in patients with no known underlying immunodeficiency. Mortality rates were high regardless of immune status. Therapy is not standardized, although the combination of amphotericin B, flucytosine, and itraconazole may improve survival rates. Newer azoles, such as voriconazole, also have a broad spectrum of activity against these fungi, although clinical experience is limited. Complete excision of brain lesions may provide better results than simple aspiration. An aggressive medical and surgical approach is warranted in treating these infections to optimize outcomes.

To update the case-fatality rate (CFR) associated with invasive aspergillosis according to underlying conditions, site of infection, and antifungal therapy, data were systematically reviewed and pooled from clinical trials, cohort or case-control studies, and case series of >/=10 patients with definite or probable aspergillosis. Subjects were 1941 patients described in studies published after 1995 that provided sufficient outcome data; cases included were identified by MEDLINE and EMBASE searches. The main outcome measure was the CFR. Fifty of 222 studies met the inclusion criteria. The overall CFR was 58%, and the CFR was highest for bone marrow transplant recipients (86.7%) and for patients with central nervous system or disseminated aspergillosis (88.1%). Amphotericin B deoxycholate and lipid formulations of amphotericin B failed to prevent death in one-half to two-thirds of patients. Mortality is high despite improvements in diagnosis and despite the advent of newer formulations of amphotericin B. Underlying patient conditions and the site of infection remain important prognostic factors.

The central nervous system (CNS) distribution and antifungal efficacy of all 4 approved formulations of amphotericin B (AmB) were investigated in a rabbit model of hematogenous Candida albicans meningoencephalitis. Treatment with AmB deoxycholate (1 mg/kg/day) or liposomal AmB (5 mg/kg/day) yielded the highest peak plasma concentration (C(max)), area under concentration versus time curve from zero to 24 h (AUC(0-24)), and time during dosing level tau Ttauminimum inhibitory complex (MIC) values and led to complete eradication of C. albicans from brain tissue (P.05 vs. untreated controls). By comparison, AmB colloidal dispersion and AmB lipid complex (5 mg/kg/day each) were only partially effective (not significant vs. untreated controls). There was a strong correlation of C(max), AUC(0-24), C(max)/MIC, AUC(0-24)/MIC, and TtauMIC with clearance of C. albicans from brain tissue (P/=.0002). Although pharmacodynamic parameters derived from the MIC of free AmB were highly predictive of antifungal efficacy, parameters derived from MICs of individual formulations were not predictive. AmB deoxycholate and liposomal AmB had the greatest antifungal efficacy. This activity was concentration and time dependent.

Cladophialophora bantiana is a phaeoid fungus that only rarely has been isolated from sources other than the human brain. It has a particular tropism for the central nervous system (CNS). We have integrated and updated large-scale data related to several aspects of C. Bantiana and reviewed all the available reports on its cerebral infections, focusing on their geographical distribution, infection routes, immune status of infected individuals, type and location of infections, clinical manifestations and treatment and outcome, briefly looking over the spectrum of other disease entities associated with C. bantiana, that is, extra-cerebral and animal infections and on the environmental sources of this fungus. Among the agents of phaeohyphomycosis, a term used to describe an infection caused by a dark pigmented fungus, C. bantiana has some significant specific features. A total of 120 case reports were identified with a significantly higher percentage of healthy subjects than immune-debilitated patients (58.3% vs. 41.7%). Infections due to C. bantiana occur worldwide. The main clinical manifestations are brain abscess (97.5%), coinfection of brain tissue and meninges (14.2%) and meningitis alone (2.5%). Among immunocompetent patients, cerebral infection occurred in the absence of pulmonary lesions. The mortality rate is 65.0% regardless of the patient's immune status. The therapeutic options used include surgery or antifungals alone, and the combination of both, in most cases the fatal outcome being rapid after admission. Since the fungus is a true pathogen, laboratory workers should be made aware that BioSafety Level-3 precautions might be necessary.

A healthy 32-year-old backpacker experienced a motorcycle accident without helmet on a country road when he was travelling in Jiangxi Province, Eastern China. He fell into a roadside ditch and aspirated some polluted water. The traveller was rescued in a local hospital. The computer tomography of the skull showed multiple fractures (Figure 1A). A month later, his temperature rose to 39.1°C, and headache got worse. He was transferred to the referral hospital and lumber puncture was performed. Analysis of the cerebrospinal fluid (CSF) showed an elevated white cells count and total protein level. Magnetic resonance imaging of the head revealed enhancement and thickening of the choroid plexus in the right lateral ventricle and the leptomeninges.... Language: en

Although blastomycosis of the central nervous system (CNS) occurs in approximately 4% of patients with blastomycosis, recurrent CNS blastomycosis is very rare. We review the clinical features, treatment, and outcome of 4 previously reported cases. We also report a case of recurrent CNS blastomycosis successfully treated with surgery and liposomal amphotericin B after an inadequate response to amphotericin B therapy. This treatment may be an alternate approach for management of similar cases.

of daptomycin by Etest (AB Biodisk) was 0.125 mg/L. Informed consent was obtained from the patient’s next of kin and therapy with daptomycin was started at a daily dose of 8 mg/kg; the other antibiotics were stopped. The high dose of daptomycin was chosen because of the elevated volume of distribution (which is typical of septic patients, together with lower plasma albumin concentrations) and because polysulphone daptomycin clearance is higher than for other types of ultrafiltration. It was not possible to determine plasma concentrations of daptomycin, and we therefore decided to monitor plasma concentrations of creatinine phosphokinase (CPK), aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase to exclude myopathy, a wellrecognized adverse effect of daptomycin. Since CPK can be eliminated by CVVH, we also measured the ultrafiltrate concentrations of CPK. The plasma concentration of CPK always remained ≤200 IU/L (normal: 50–397 IU/L) and the ultrafiltered CPK concentration never exceeded 86 IU/L. The patient’s condition improved and therapy was discontinued after 14 days. Dosing of antibiotics for patients in intensive care can be challenging, particularly when they undergo renal replacement therapy. Ideally, plasma concentrations should be checked regularly, but this may be impractical in real time. Data from in vitro models of CRRT suggest that a substantial amount of daptomycin can be removed. Since we could not monitor antibiotic concentrations in order to avoid subtherapeutic exposure, we decided to use a higher daily dose (8 mg/kg) and no adverse effects were demonstrated. Despite the limitations of this report we suggest that higher doses can be given safely in CRRT, but patients should be closely monitored for evidence of myopathy. Further studies, with plasma monitoring, are required to refine dosage regimens for CRRT.