Elisabeta Benea

Meningitis due to an unusual human pathogen: Streptococcus equi subspecies equi.

Streptococcus equi subspecies equi is involved in human infection. We present a case of meningitis in a 75-year-old patient with a favorable outcome after ceftriaxone and dexamethasone therapy. To our knowledge, it is the first case reported in an adult.

In the era of broad spectrum antibiotics, is ampicillin still an option?

Background In the era of broad spectrum antibiotics it is sometimes difficult to choose the best antimicrobial regimens. Because of misuse and abuse of antimicrobial usage, the level of resistance is increasing and sometimes we do not have treatment options. Infectious diseases specialists traditionally have the leadership role in optimal use of antimicrobials. Antimicrobial stewardship represents a worldwide accepted concept in order to preserve currently available antibiotics.

Muco-cutaneous manifestations in HIV infection/AIDS

The HIV/AIDS infection is an important public health problem in Romania. The aim of this study was to evaluate the main muco-cutaneous manifestations and their frequency in patients with HIV infection/AIDS in Romania. The study was performed beginning 1988 among 400 patients with HIV infection/AIDS who attended Scarlat Longhin Clinical Hospital for Dermatology, Victor Babes Clinical Hospital of Infectious Diseases and Matei Bals National Institute for Infectious Diseases Bucharest, Romania. The patients were clinically examined; mycological examination (KOH exam, cultures) was necessary in 216 cases and histological examination was performed in 32 cases. The subjects were classified in all stages of disease. The age of patients included in the study ranged from 6 months to 82 years. Muco-cutaneous manifestations were present in 76% of patients. The main muco-cutaneous manifestations registered were infections - 283 cases (oral and/or genital candidiasis - 179 cases; molluscum contagiosum - 53 cases; warts - 37 cases; tinea - 36 cases; sexually transmitted infections - 107 cases: herpes simplex genitalis - 33 cases, urethritis - 31 cases, condylomata acuminata - 29 cases, syphilis - 17 cases; herpes zoster - 28 cases; scabies - 12 cases; intertrigo - 11 cases; hairy leukoplakia - 4 cases; acute retroviral infection - 2 cases; disseminated cryptococcosis - 2 cases; bacillary angiomatosis, ganglionar tuberculosis - 1 case each), xerosis - 172 cases, papular eruptions - 87 cases, seborrheic dermatitis - 57 cases, atopic dermatitis - 24 cases, drug reactions - 21 cases, cancers - 20 cases (Kaposi sarcoma - 16 cases, basal cell carcinoma - 4 cases), psoriasis - 7 cases. Muco-cutaneous manifestations in HIV infection/AIDS are frequent and polymorphous. They can occur at any point in time, but their frequency and severity are increasing as HIV infection progresses. Dermatological examination is an important step in evaluation of patients HIV-positive.

Difficulties in controlling HIV and TB infections in multi-experienced patients

The treatment of extra pulmonary tuberculosis in HIV infected patients experienced to antiretroviral therapy raises major issues of adherence, drug interactions, side effects and limited antiretroviral alternatives. This is the case of a 24 year old woman from countryside, most probably infected in 1989. She was diagnosed with HIV infection in 2000 after repeated admissions in hospital for pneumonia. She started ART when diagnosed with a favorable evolution: CD4 cell count increased from 200 to 674 cells/cmm, and HIV RNA levels became undetectable. She turned 18 in 2008 and refused to take her treatment for almost two years. She returned to the hospital in April 2010 with a CD4 cell count of 140 cells/cmm. She started again antiretroviral therapy with ABC+3TC+FPV/r. In April 2013 she is admitted with night sweats, chills and fever. At that time her CD4 cell count was 144 cells/cmm and had 461,000 copies/mL RNA-HIV. Her chest XR showed right pleural effusion, widened mediastinum and the CT revealed infiltrative-like lesion at subcarinal and retrocarinal level. Biopsy was performed and she was diagnosed with ganglionary tuberculosis. She started anti-TB treatment HRZE 7/7 and the ART was changed to ABC+RAL+T20. The anti-TB regimen is changed after three months to rifampicin and isoniazid 7/7 because she accused arthralgias, tingling of the extremities, blurred vision and decreased visual acuity. She was diagnosed with hyperuricemia (pyrazinamide) and optic and peripheral neuritis (ethambutol). New visit at the clinic for fatigability, after 7 months of antiretroviral therapy with ABV+RAL+T20. The CD4 cell count was 9 cells/cmm and RNA-HIV was 61,000 copies/mL. She admits taking 1 cp of Raltegravir BID, but denies any other adherence problem. The resistance test showed evidence of resistance to some NRTIs, to all NNRTIs, to RAL and no resistance to PIs. The tropism test showed that maraviroc can be used. We have excluded relapse of tuberculosis and other diseases associated. The ART was changed again to TDF+DRV/r+MRV and the anti-TB treatment is change to isoniazid and moxifloxacin. Adherence can be an important issue when treating patients for long periods of time. Other important issues are the drug-drug interactions (rifampicin – PIs) and the increased side effects which may lead to loss of good friends (Raltegravir). The poor outcome for this patient may be due to poor HIV and tuberculosis control.

Difficulties in the management of the meningitis with C. neoformans

The management of the meningitis with C. neoformans raises many problems: the choosing of the appropriate antifungal therapy, the prevention and/or the control of the complications, the correct management of the antiretroviral therapy. We report two cases with HIV infection same immunological and clinical stage, the first of them with relatively recent infection, the second with long-term infection (>20 years) and antiretroviral therapy experienced, but discontinued for 4 years, who developed the same opportunistic infection: cryptococcal meningitis. Although immunological status was similar in both patients, cerebrospinal fluid inflammatory response was stronger in patient infected latest; both had increased cerebrospinal fluid pressure, requiring repeated lumbar punctures. The antifungal treatment algorithm was applied according to guidelines, to availability of medications at that time and antifungal susceptibility testing results. Although the combination of fluconazole plus flucytosine is knowed as being clinically inferior to amphotericin B–based therapy, faster rate of cerebrospinal fluid sterilization was seen in patient with greater cerebrospinal fluid inflammatory response rather than in patient receiving antifungal therapy considered as “gold standard”. To avoiding the immune reconstitution syndrome, antiretroviral therapy was initiated in both cases after more than 4 weeks of therapy of opportunistic infection (after 2 weeks of sterilizing cerebrospinal fluid cultures); however, the patient with long-term HIV infection developed immune reconstitution syndrome after 21 days of initiating therapy. Choosing antiretroviral therapy was achieved in both cases according to guidelines, depending on the patient’s medical history (including previous regimens therapy) and drug interactions. Our cases illustrate that the same disease can have different solutions because the patient makes the difference.

A retrospective study concerning specific therapy and evolution of invasive fungal infections diagnosed in the National Institute for Infectious Diseases "Prof. Dr. Matei Bals".

Results 18 patients met the inclusion criteria for the studied period, representing 40% of the patients with potentially invasive fungal infections. The majority of patients were male, and the average age was 44 years. Only 2 of the patients apparently were not immunocompromised, the other 16 presenting HIV infection or fungal infections risk factors. The fungal species identified were Cryptococcus neoformans in 8 cases (40%) and Candida spp in 12 cases (60%), out of which 75% consisted of non-albicans species. The invasive fungi were isolated from blood cultures in 9 cases (52.4%), cerebrospinal fluid in 8 cases (38.1%), tips of central venous catheters in one case and from other pathological products in one case. The average period from admission to identification was 9.6 days. The antifungal susceptibility test indicated that 16 out of the 20 cases (80%) were sensitive to fluconazole and only 20% were dose-dependent sensitivity types. The patients were treated mainly using monotherapy – 1 antifungal in 10 cases (55%). Fluconazole was the most used agent, in 14 cases (77.8%) followed by voriconazole in 7 cases and posaconazole in 4 cases. The average treatment duration was 37.7 days, the shortest being one day, and the longest 120 days. 6 out of 18 patients (33.3%) deceased: one patient presenting severe bacterial infection treated with prolonged antibiotherapy and 5 presenting C. neoformans meningitis associated with HIV infection.

Characteristics of Kaposi sarcoma in HIV-infected patients

Objective: to describe clinical and laboratory characteristics; to assess predictors for death in HIV-infected patients with Kaposi sarcoma (KS). We performed a retrospective study of HIV-infected patients diagnosed with KS in one infectious diseases hospital in Romania, between January 2008-November 2013. KS diagnosis was established on physical examination, skin biopsy, and for visceral involvement upper gastrointestinal endoscopy, bronchoscopy and computed tomography. KS was staged according to the AIDS Clinical Trials Group (ACTG) [1] and the Mitsuyasu classification system [2]. We identified 27 HIV-infected patients with KS. The median age was 42 years (IQR 34-52) and 18 (67%) were male. The median CD4 count at HIV diagnosis was 195 cells/cmm (IQR 55-313), while at KS diagnosis the median CD4 count was 101 cells/cmm (IQR 41-270). Eighteen (67%) patients had a CD4 count <200 cells/cmm. The median HIV viral load at the time of KS diagnosis was 120,000 copies/mL (IQR 316-328,522). HIV infection was diagnosed before KS in 19 patients (70%), with a median time between HIV and KS diagnosis of 7 months (IQR 0-58). The most frequent KS localization was the lower limb in 16 (59%) patients and 7 (26%) patients had disseminated KS. Oral, gastrointestinal and pulmonary involvements were seen in 10 (37%), 4 (15%) and 3 (11%) patients respectively. Concomitant opportunistic infections were diagnosed in 20 (74%), while other malignancies in 3 (12%) patients. According to the ACTG classification 16 (59%) patients had poor risk KS. Fifteen (56%), 6 (22%), 1 (4%) and 5 (18%) were in stage 1, 2, 3 and 4, respectively according to the Mitsuyasu classification. Six (22%) patients received specific KS treatment: three local radiotherapy and three systemic therapy (two with interferon; one with liposomal doxorubicin). The overall mortality was 41% with a median duration between KS diagnosis and death of 6 months (IQR 2-15). Gastrointestinal involvement (p=0.019), poor-risk KS in ACTG classification (p<0.001) and stage IV Mitsuyasu (p=0.006) were associated with death in univariate analysis. The mortality rate in this study was high, due to poor immunological status, extended KS and high incidence of opportunistic infections, but also due to the lack of specific systemic treatment.

Opportunistic infections and immune reconstitution inflammatory syndrome (IRIS) in HIV infected patient – late presenter in cART era: case report

HIV-infected individuals are at high risk of developing numerous opportunistic infections. The severity of these infections may increase proportional to the immunosuppression degree. We must pay special attention to immune reconstitution inflammatory syndrome (IRIS) in order to prevent worsening symptoms and death. HIV coinfection is associated with high mortality rate despite effective antiretroviral therapy. We present the case of a 42 male patient who was diagnosed with AIDS and pulmonary tuberculosis in 2011 in our clinic. Our theme includes clinical, biological, immunological, virological evolution and therapeutics of this patient. He was a late-presenter patient with advanced immunodepression at baseline: low CD4 count, increased viral load in blood and cerebrospinal fluid. After a month of tuberculosis treatment, antiretroviral therapy was instituted according to guidelines. During one year the patient subsequently developed IRIS and, one by one, several opportunistic infections, including CNS involvement. Thus he presented: Cryptococcus neoformans meningoencephalitis resistant to fluconazole with multiple relapses, TB meningoencephalitis, severe form of CMV disease with encephalitis, demyelinating lesions, necrotic ulcerative stomatitis and esophagitis with HSV, systemic candidiasis, severe bacterial infections with multidrug-resistant germs. Diagnoses were based on the usual investigations, including molecular biology techniques (RT-PCR: Mycobacterium tuberculosis, JC virus, Cryptococcus neoformans), viral resistance testing, PLEX-ID, MRI. Viral PLEX-ID identified the presence of Epstein Barr virus in CSF at a high level. Opportunistic infections occurred imposed specific therapy and reconsideration of antiretroviral therapy with CNS penetration ARV (score Letendre). The patient was adherent to ARV therapy. The evolution was initially favorable under specific therapy with clinical, immunological and virological improvement. Unfortunately, about 10 months after diagnosis, the patient developed CNS lymphoma possibly in relationship with increased levels of Epstein Barr virus in CSF, having fatal outcome. The evolution of this case pointed out once again that in a patient with AIDS at the time of initiating ART, it should be considered the possibility of IRIS and future opportunistic infections, associated with a poor prognosis. Therefore it is important to detect persons with HIV infection in the early stages of the disease in order to obtain a favorable evolution.

Epstein-Barr virus in the cerebrospinal fluid of HIV-positive patients. Observational cross-sectional study

Different viruses are detected in the cerebrospinal fluid (CSF) of HIV-positive patients, with controversial implications in central nervous system (CNS) impairment. Objectives: to evaluate the presence, frequency and associations of Epstein-Barr virus (EB) in the CSF in HIV-positive patients. We retrospectively analyzed CSF samples from HIV-positive adult patients (≥18 years old), with or without CNS impairment, collected between Oct 2011 and Oct 2012 in a Romanian tertiary infectious diseases hospital. We performed a multiplex PCR coupled with electrospray ionization – time-of-flight mass spectrometry (Abbott Molecular) which can simultaneously detect: herpesviruses (1-5 and 8), polyomaviruses, enteroviruses, adenoviruses and parvoviruses. The patients were characterized based on the immunological and virological HIV status, neurological findings (including neuroimagery and CSF exam) and comorbidities. A number of 55 patients were analyzed, with a mean age of 33.4 years (31.5 median) and a male:female ratio of 1.9:1. The CD4 count had a mean of 32 (75 median and IQR=225). The most frequently detected virus was EB in 20/55 cases. The EB-positive subgroup had a similar mean age of 33.5 years (median of 31.0) but a different male:female ratio, of 1.2:1. The CD4 count had a mean of 105.7 (59.5 median and IQR=156). The following analyses refer to the EB-positive group: 17/20 patients had neurologic impairment. Imagery was performed in 15 cases and was normal in 5. CSF cellularity had a median of 2/cmm, IQR=10, CSF-glucose a median of 48.0 mg/dL, IQR=34 and CSF-protein a median of 55.5mg/dL, IQR=49.5. In 8/20 cases EB was found as singular agent in the CSF and in 12/20 it was associated with other microorganisms: other herpesviruses (3 cases), JC virus (4 cases), Mycobacterium tuberculosis (2 cases), Cryptococcus neoformans (2 cases) and Toxoplasma gondii (one case). The CSF-HIV viral load was available in 12/20 cases, being detectable in 10 cases. Regarding the neurological events (totalizing the neurological signs/symptoms, CSF exam and imagery), EB was probably causal in 4/20 cases, possibly causal in another 4/20 cases and was a bystander in 12/20 (3 cases with no impairment and 9 cases in which the impairments were strongly attributable to another germ). EB is the most frequent agent found in the CSF (40% of HIV-positive cases), mainly in women. It can be mono-detected but it especially appears in multiple associations. In more than half of the cases EB acts as an innocent bystander.

Syphilitic encephalitis - a rare disease and a possible differential diagnosis of herpetic encephalitis.

Case report We present the case of a 41 year-old male, diagnosed with syphilitic encephalitis, in whom cerebral magnetic resonance imaging demonstrated preponderant involvement of bilateral temporal lobes, for this point of view raising differential diagnostic concerns with Herpes virus encephalitis. We also identified multiple encephalitis foci: hippocampus, lentiform nucleus, left thalamus, left midbrain, and bilateral occipital. The detection of herpes simplex virus DNA by PCR in CSF obtained at admission was negative. Furthermore, the subacute onset as a maniacal syndrome delayed the diagnostic, the patient being initially treated as psychiatric disorder in a Psychiatric Unit.