AimTo investigate the relationship between plasma and cyst concentrations of albendazolesulphoxide (ASO) and their effects on parasitological findings and disease recurrence in patients with liver hydatidosis.MethodsThe study was conducted at the University Hospital for Infectious Diseases “Dr. Fran Mihaljević,” Zagreb, Croatia, between August 2006 and January 2011. Consecutive patients (N = 48, age 6-77 years) were treated with albendazole (3 × 5 mg/kg/d) over 28 days before surgical cyst removal (n = 34) or percutaneous evacuation (PAIR) (n = 14). Plasma ASO was determined on days 10 and 28 of treatment and cyst concentrations at surgery/PAIR.ResultsDisease recurred in 3 surgically treated patients. Variability of ASO concentrations was substantial. Plasma concentrations on day 10 were higher than on day 28 (geometric means ratio [GMR] 2.00; 95%CI 1.38-2.91, P < 0.001) and higher than cyst concentrations at the time of treatment (GMR = 1.58, 1.01-2.34, P = 0.045). Higher cyst (but not plasma) concentrations were independently associated with lower odds of protoscolex motility (OR = 0.23, 0.01-0.70, P < 0.001) and higher odds of protoscolex destruction (OR = 1.17, 1.04-1.46, P < 0.001). With adjustment for age and protoscolex motility, higher day 10 plasma concentrations (but not cyst concentrations) were associated with lower odds of disease recurrence (OR = 0.49, 0.09-0.97, P = 0.035). Plasma concentrations did not predict cyst concentrations.ConclusionViability of protoscolices progressively decreased with increasing ASO concentrations in the cyst. Data strongly suggested that higher plasma concentrations reduced the risk of disease recurrence.

Cystic echinococcosis (CE) is a widespread zoonosis caused by the species complex Echinococcus granulosus. Albendazole (ABZ)—the first-line anthelminthic drug for medical treatment of CE—is metabolized in vivo to the active derivative ABZ-sulphoxide (ABZ-SO). Target-site ABZ-SO concentrations in the hydatid cyst mediate the anthelminthic effect in CE. Primary outcome of this systematic review of individual patient data was the intra-cystic ABZ-SO concentration stratified by cyst size, location, calcification status and use of praziquantel. Studies reporting intra-cystic ABZ-SO concentrations in humans were identified by a systematic search. A pooled analysis of individual patient data was performed to assess intra-cystic concentrations. Pharmacokinetic data of 121 individual cysts were analysed. There was no correlation between plasma and intra-cystic ABZ-SO concentrations (rho = −0.03, p = 0.76). Intra-cystic drug concentrations were also not associated with sex and treatment duration. Use of praziquantel in combination with ABZ was associated with higher plasma (median 540 vs. 240 μg/L; p = 0.04) but not intra-cystic ABZ-SO concentrations (median 220 vs. 199 μg/L; p = 0.36). Relative drug concentrations in hepatic cysts were higher than in other cysts (0.8 vs. 0.4; p = 0.05). Intra-cystic concentrations were higher in calcified than non-calcified cysts (median 897 vs. 245 μg/L; p = 0.03). There was a trend towards higher intra-cystic concentrations in smaller sized cysts (β = −17.2 μg/L/cm; 95th CI, −35.9 to 1.6; p = 0.07). This study demonstrates that mean intra-cystic drug concentrations are similar to plasma concentrations on a population level. However, in individual patients plasma concentrations are not directly predictive for intra-cystic concentrations. The use of booster drugs was not associated with higher intra-cystic ABZ-SO concentrations in this analysis.Electronic supplementary materialThe online version of this article (doi:10.1007/s00436-016-5054-x) contains supplementary material, which is available to authorized users.

Aim To evaluate the clinical characteristics of adult and adolescent Croatian patients hospitalized for herpes zoster over a period of 21 years in the largest national center for infectious diseases (catchment area approximately 25% of the Croatian population). Methods This retrospective chart review included all patients older than 15 years hospitalized for herpes zoster at the University Hospital for Infectious Diseases “Dr. Fran Mihaljević” between January 1, 1996 and December 31, 2016. Results The study enrolled 1755 patients (uniform annual hospitalizations), 50% of whom suffered from complicated forms of herpes zoster, mostly generalized zoster (22.0%), infected lesions (14.8%), and meningitis/encephalitis (10.4%). A low percentage of patients experienced Ramsey-Hunt syndrome (3.0%), keratitis (1.5%), and visceral dissemination (0.2%). The majority of patients were older than 55 years (80%, median 70 years). Overall, 61.6% of patients suffered from at least one comorbidity (most frequent: diabetes 14.6%, cardiovascular incidents 24.4%, malignancy 13.0%, other infection 12.9%), and 28.2% suffered from ≥2 comorbidities. All-cause in-hospital mortality was 0.9%. The proportion of patients with any complicated form and of patients with meningitis/encephalitis steadily decreased over time, while the proportion of patients with comorbidities increased. This coincided also with steadily increasing age. No association was observed between comorbidities and complicated forms of zoster. Pharmacological immunosuppression was associated with generalized zoster; younger age was associated with meningitis/encephalitis; and older age was associated with generalized zoster and infected lesions. Conclusion The patients most frequently hospitalized for herpes zoster are elderly people burdened with comorbidities, not necessarily patients with complicated forms of the disease.

We describe a case of an abrupt onset of polymicrobial Actinomyces naeslundii/Pseudomonas aeruginosa sepsis in a patient with a previously silent abdominal actinomycosis, developed 2 months after colonoscopy when the diagnosis of a left-sided ulcerative colitis was established. Prolonged high-dose ceftriaxone therapy was clinically effective, albeit accompanied by the development of a reversible pseudocholelithiasis that persisted for 5 months.

Because of mostly asymptomatic cyst growth and often-neglected nonspecific low-grade symptoms, many cases of cystic echinococcosis (CE) caused by Echinococcus granulosus in the pediatric population are diagnosed at school age, in an advanced and even complicated stage. In 2003, after 5 months of intermittent dull upper-right abdominal pain and nausea, a 13-year-old boy was diagnosed with massive liver CE, with ∼20 round-shaped double-walled medium-sized infective cysts, which permeated the whole liver. Because of their wide distribution across the liver tissue and the risky superficial position of some cysts, liver transplantation emerged as the optimal therapeutic option. Despite being described as only an exceptionally used method for CE, we subjected our patient on 4 occasions to a radiofrequency energy thermoablation (RFT) procedure similar to the one used for malignant neoplasms. In total, 9 superficially situated cysts were initially treated with RFT by using a 14-gauge outer needle and a temperature of 70°C for 8 minutes per cyst, and the remaining cysts were treated with the puncture-aspiration-instillation-reaspiration procedure, along with albendazole (15 mg/kg per day) therapy, for a period of 20 months. After 2 years of follow-up, 4 residual small-sized semisolidified cysts were seen in the liver, and the patient showed no signs of relapse. Although not routinely used, RFT, along with puncture-aspiration-instillation-reaspiration and prolonged albendazole therapy, has shown good tolerability and long-term efficacy in the treatment of multiple infective CE, which could suggest the usefulness of the RFT method beyond salvage situations in pediatric patients.

We present a 40-year-old woman with a history of relapsing echinococcosis who had undergone a number of surgical procedures for cyst removal (right pulmectomy, cardiac surgery and 6 subsequent brain surgeries and two gamma knife procedures) and was admitted to University Hospital for Infectious Diseases “Fran Mihaljević”, Zagreb, Croatia in 2014 for pre-operative medical treatment of brain hydatidosis in the right parietal region. We aimed to attain a high cyst albendazole sulphoxide (ASO) concentration in order to achieve a more pronounced protoscolex inactivation and a high serum ASO concentration (reflecting the tissue concentrations) to reduce the risk of disease recurrence. The patient was treated with a higher dose of albendazole (15 mg/kg/day for 4 wk) that we had found effective in patients with liver hydatidosis, and combined with praziquantel over the last 14 d at a dose that is typically used to treat neurocysticercosis with an intention to improve ASO bioavailability. Neither serum nor cerebrospinal fluid concentrations on day 10 apparently differed from those on day 24 indicating a lack of an effect of praziquantel on ASO bioavailability. Intra-cystic ASO concentration was below the lower limit of quantification, but above the limit of detection. After the 7th episode of the disease and combined albendazole-praziquantel and surgery treatment, the patient achieved a 3-year remission. With the apparent lack of a meaningful pharmacokinetic praziquantel-albendazole interaction, this is most likely ascribable to the use of a higher albendazole dose than previously.

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186-187. ISSN 0036-5548