Rok Čivljak

Post-Exposure Prophylaxis of HIV Infection in Healthcare Workers: Recommendations for the European Setting

The European Commission funded a project for the standardisation of the management of occupational exposures to HIV/blood-borne infections and antiretroviral post-exposure prophylaxis (PEP) in Europe. Within this project, the following recommendations and rationale were formulated by experts representative of participating countries. Based on assessment of the exposure, material, and source characteristics, PEP should be started as soon as possible with any triple combination of antiretrovirals approved for the treatment of HIV-infected patients; initiation is discouraged after 72 hours Rapid HIV testing of the source could reduce inappropriate PEP. HIV testing should be performed at baseline, 4, 12, and 24 weeks, with additional clinical and laboratory monitoring of adverse reactions and potential toxicity at week 1 and 2. HIV resistance tests in the source and direct virus assays in the exposed HCW are not recommended routinely. These easy-to-use recommendations seek to maximise PEP effect while minimising its toxicity and inappropriate use.

The microbiological diagnosis of tuberculous meningitis: results of Haydarpasa-1 study

We aimed to provide data on the diagnosis of tuberculous meningitis (TBM) in this largest case series ever reported. The Haydarpasa-1 study involved patients with microbiologically confirmed TBM in Albania, Croatia, Denmark, Egypt, France, Hungary, Iraq, Italy, Macedonia, Romania, Serbia, Slovenia, Syria and Turkey between 2000 and 2012. A positive culture, PCR or Ehrlich-Ziehl-Neelsen staining (EZNs) from the cerebrospinal fluid (CSF) was mandatory for inclusion of meningitis patients. A total of 506 TBM patients were included. The sensitivities of the tests were as follows: interferon-γ release assay (Quantiferon TB gold in tube) 90.2%, automated culture systems (ACS) 81.8%, Löwenstein Jensen medium (L-J) 72.7%, adenosine deaminase (ADA) 29.9% and EZNs 27.3%. CSF-ACS was superior to CSF L-J culture and CSF-PCR (p <0.05 for both). Accordingly, CSF L-J culture was superior to CSF-PCR (p <0.05). Combination of L-J and ACS was superior to using these tests alone (p <0.05). There were poor and inverse agreements between EZNs and L-J culture (κ = -0.189); ACS and L-J culture (κ = -0.172) (p <0.05 for both). Fair and inverse agreement was detected for CSF-ADA and CSF-PCR (κ = -0.299, p <0.05). Diagnostic accuracy of TBM was increased when both ACS and L-J cultures were used together. Non-culture tests contributed to TBM diagnosis to a degree. However, due to the delays in the diagnosis with any of the cultures, combined use of non-culture tests appears to contribute early diagnosis. Hence, the diagnostic approach to TBM should be individualized according to the technical capacities of medical institutions particularly in those with poor resources.

Could chloramphenicol be used against ESKAPE pathogens? A review of in vitro data in the literature from the 21st century

The widespread use of antibiotics has been associated with the emergence of antimicrobial resistance among bacteria. ‘ESKAPE’ (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acintobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) pathogens play a major role in the rapidly changing scenario of antimicrobial resistance in the 21st century. Chloramphenicol is a broad spectrum antibiotic that was abandoned in developed countries due to its association with fatal aplastic anemia. However, it is still widely used in the developing world. In light of the emerging problem of multi-drug resistant pathogens, its role should be reassessed. Our paper reviews in vitro data on the activity of chloramphenicol against ESKAPE pathogens. Susceptibility patterns for Gram-positives were good, although less favorable for Gram-negatives. However, in combination with colistin, chloramphenicol was found to have synergistic activity. The risk-benefit related to chloramphenicol toxicity has not been analyzed. Therefore, extra precautions should be taken when prescribing this agent.

Polymicrobial community-acquired pneumonia: An emerging entity

Polymicrobial aetiology in community‐acquired pneumonia (CAP) is more common than previously recognized. This growing new entity can influence inflammation, host immunity and disease outcomes in CAP patients. However, the true incidence is complicated to determine and probably underestimated due mainly to many cases going undetected, particularly in the outpatient setting, as the diagnostic yield is restricted by the sensitivity of currently available microbiologic tests and the ability to get certain types of clinical specimens. The observed rate of polymicrobial cases may also lead to new antibiotic therapy considerations. In this review, we discuss the pathogenesis, microbial interactions in pneumonia, epidemiology, biomarkers and antibiotic therapy for polymicrobial CAP.

High infection rate of bank voles (Myodes glareolus) with Puumala virus is associated with a winter outbreak of haemorrhagic fever with renal syndrome in Croatia.

An outbreak of haemorrhagic fever with renal syndrome (HFRS) started on Medvednica mountain near Zagreb in January 2012. In order to detect the aetiological agent of the disease in small rodents and to make the link with the human outbreak, rodents were trapped at four different altitudes. Using nested RT-PCR, Puumala virus (PUUV) RNA was detected in 41/53 (77·4%) bank voles (Myodes glareolus) and Dobrava virus (DOBV) RNA was found in 6/61 (9·8%) yellow-necked mice (Apodemus flavicollis). Sequence analysis of a 341-nucleotide region of the PUUV S segment, obtained from all infected bank voles and five HFRS patients, showed 98·8-100% sequence similarity, indicating that the patients were probably exposed to PUUV on Medvednica mountain. A very large bank-vole population combined with an extremely high infection rate of PUUV was responsible for this unusual winter outbreak of HFRS in Croatia.

Influenza and hepatitis B vaccination coverage among healthcare workers in Croatian hospitals: a series of cross-sectional surveys, 2006–2011

BackgroundHealthcare workers (HCWs) are at an increased risk of exposure to and transmission of infectious diseases. Vaccination lowers morbidity and mortality of HCWs and their patients. To assess vaccination coverage for influenza and hepatitis B virus (HBV) among HCWs in Croatian hospitals, we conducted yearly nationwide surveys.MethodsFrom 2006 to 2011, all 66 Croatian public hospitals, representing 43–60% of all the HCWs in Croatia, were included. Statistical analysis was performed using the Kruskal–Wallis analysis of variance, Dunn’s multiple comparison analysis and the chi-square test, as appropriate.ResultsThe median seasonal influenza vaccination coverage rates in pre-pandemic (2006–2008) seasons were 36%, 25% and 29%, respectively. By occupation, influenza vaccination rates among physicians were 33 ± 21%, 33 ± 22% among graduate nurses, 30±34% among other HCWs, 26 ± 21% among housekeeping and the lowest, 23 ± 17%, among practical nurses (p < 0.01). In 2009–2010 season, seasonal influenza vaccination coverage was 30%, while overall vaccination coverage against pandemic influenza was fewer than 5%. Median vaccination coverage in the post-pandemic seasons of 2010–2011 and 2011–2012 decreased to 15% and 14%, respectively (reduction of 24% and 35%, respectively, p < 0.0001). Meanwhile, the median mandatory HBV vaccination coverage was 98%, albeit with considerable differences according to work setting (range 19–100%) and occupation (range 4–100%).ConclusionsWe found substantial year-on-year variations in seasonal influenza vaccination rates, with reduction in post pandemic influenza seasons. HBV vaccination is satisfactory compared to seasonal influenza vaccination coverage, although substantial variations by occupation and work setting were observed. These findings highlight the need for national strategies that optimize vaccination coverage among HCWs in Croatian hospitals. Further studies are needed to establish the potential role of mandatory vaccination for seasonal influenza.

Occupational exposure to blood among hospital workers in montenegro.

Abstract This cross-sectional study was performed in nine Montenegrin hospitals to estimate the burden of occupational exposure to blood among hospital workers in Montenegro in 2010 using a modified Croatian self-reporting questionnaire on exposure to blood-borne infections. Of the 1043 respondents, 517 (49.6 %) reported exposure to blood. Variations between the hospitals were not significant, except for the hospital in Kotor, which stands out with the high percentage of exposed hospital workers (p<0.05). More than 77 % of exposures were not reported through standard hospital protocols at the time of the incident. The most exposed group to blood were nurses (357 of 517; 69.1 %), but the percentage of exposed nurses within the group did not stand out compared to other occupations and was close to that reported by physicians (50.57 % vs. 57.49 %, respectively). The number of hospital workers with appropriate HBV vaccination was surprisingly low (35.7 %) and significantly below the recommended best practice (at least two consecutive doses of HBV vaccine documented for 100 % of employees) (p<0.001). Even with its limitations, our study fills a gap in knowledge about the actual number of sharps incidents and other occupational exposure to blood among hospital workers in Montenegro as well as about the issue of underreporting, which is very common. It also confirms the urgent need for active implementation of special, comprehensive measures to prevent needle-stick and other sharps injuries. Constant staff training, life-long learning, and standardising post-exposure procedures are also recommended.

Hydrocephalus and vasculitis delay therapeutic responses in tuberculous meninigitis: Results of Haydarpasa-III study

AIMS There is no report on the factors affecting the resolution of symptoms related to meningitis during treatment of tuberculous meningitis (TBM). Thus, we examined the factors associated with early therapeutic responses. MATERIALS AND METHODS This multicenter study included 507 patients with microbiologically confirmed TBM. However, 94 patients eligible for the analysis were included in this study from 24 centers. Six out of 94 patients died and the statistical analysis was performed with 88 survivors. Early and late responder groups were compared in the statistical analysis. P < 0.05 were considered to show a significant difference. RESULTS In the multivariate analysis, the presence of vasculitis (P = 0.029, OR = 10.491 [95% CI, 1.27-86.83]) was found to be significantly associated with a delayed fever response whereas hydrocephalus was associated with altered mental status for >9 days duration (P = 0.005, OR = 5.740 [95% CI, 1.68-19.57]). According to linear regression analysis, fever was significantly persisting (>7 days) in the presence of vasculitis (17.5 vs. 7, P< 0.001) and hydrocephalus (11 vs. 7, P = 0.029). Hydrocephalus was significantly associated with persisting headache (21 vs. 12, P = 0.025), delayed recovery of consciousness (19.5 vs. 7, P = 0.001), and a delay in complete recovery (21 vs. 14, P = 0.007) in the linear regression analysis. Following institution of treatment, the complaints seemed to disappear in up to 2 weeks among TBM survivors. CONCLUSIONS In the absence of hydrocephalus or vasculitis, one week of anti-tuberculosis treatment seems to be adequate for the resolution of TBM symptoms. Hydrocephalus and vasculitis delay the resolution of TBM symptoms in response to antimycobacterial treatment.

Relapsing Bacteraemia due to Corynebacterium striatum in a Patient with Peripheral Arterial Disease.

We describe the first reported case of Corynebacterium striatum (C. striatum) relapsing bacteraemia in a patient with peripheral arterial disease and proven Corynebacterium species colonization of a chronic foot ulcer, focusing on the difficulties in the management of the patient. We conclude that the optimal duration of the antibiotic treatment for relapsing C. striatum bacteraemia from a chronic ulcer should be 6 weeks together with surgical treatment.

Acute promyelocytic leukemia after whole brain irradiation of primary brain lymphomainan HIV-infected patient

The occurrence of acute promyelocytic leukemia (APL) in HIV-infected patients has been reported in only five cases. Due to a very small number of reported HIV/APL patients who have been treated with different therapies with the variable outcome, the prognosis of APL in the setting of the HIV-infection is unclear. Here, we report a case of an HIV-patient who developed APL and upon treatment entered a complete remission. A 25-years old male patient was diagnosed with HIV-infection in 1996, but remained untreated. In 2004, the patient was diagnosed with primary central nervous system lymphoma. We treated the patient with antiretroviral therapy and whole-brain irradiation, resulting in complete remission of the lymphoma. In 2006, prompted by a sudden neutropenia, we carried out a set of diagnostic procedures, revealing APL. Induction therapy consisted of standard treatment with all-trans-retinoic-acid (ATRA) and idarubicin. Subsequent cytological and molecular analysis of bone marrow demonstrated complete hematological and molecular remission. Due to the poor general condition, consolidation treatment with ATRA was given in March and April 2007. The last follow-up 14 months later, showed sustained molecular APL remission. In conclusion, we demonstrated that a complete molecular APL remission in an HIV-patient was achieved by using reduced-intensity treatment.