Yasemin Cag

Results of a Multinational Study Suggest the Need for Rapid Diagnosis and Early Antiviral Treatment at the Onset of Herpetic Meningoencephalitis

ABSTRACT Data in the literature regarding the factors that predict unfavorable outcomes in adult herpetic meningoencephalitis (HME) cases are scarce. We conducted a multicenter study in order to provide insights into the predictors of HME outcomes, with special emphasis on the use and timing of antiviral treatment. Samples from 501 patients with molecular confirmation from cerebrospinal fluid were included from 35 referral centers in 10 countries. Four hundred thirty-eight patients were found to be eligible for the analysis. Overall, 232 (52.9%) patients experienced unfavorable outcomes, 44 died, and 188 survived, with sequelae. Age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02 to 1.05), Glasgow Coma Scale score (OR, 0.84; 95% CI, 0.77 to 0.93), and symptomatic periods of 2 to 7 days (OR, 1.80; 95% CI, 1.16 to 2.79) and >7 days (OR, 3.75; 95% CI, 1.72 to 8.15) until the commencement of treatment predicted unfavorable outcomes. The outcome in HME patients is related to a combination of therapeutic and host factors. This study suggests that rapid diagnosis and early administration of antiviral treatment in HME patients are keys to a favorable outcome.

Genitourinary brucellosis: results of a multicentric study

This study reviewed the clinical, laboratory, therapeutic and prognostic data on genitourinary involvement of brucellosis in this largest case series reported. This multicentre study pooled adult patients with genitourinary brucellar involvement from 34 centres treated between 2000 and 2013. Diagnosis of the disease was established by conventional methods. Overall 390 patients with genitourinary brucellosis (352 male, 90.2%) were pooled. In male patients, the most frequent involved site was the scrotal area (n=327, 83.8%), as epididymo-orchitis (n=204, 58%), orchitis (n=112, 31.8%) and epididymitis (n=11, 3.1%). In female patients, pyelonephritis (n=33/38, 86.8%) was significantly higher than in male patients (n=11/352, 3.1%; p<0.0001). The mean blood leukocyte count was 7530±3115/mm3. Routine laboratory analysis revealed mild to moderate increases for erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). The mean treatment duration and length of hospital stay were significantly higher when there were additional brucellar foci (p<0.05). Surgical operations including orchiectomy and abscess drainage were performed in nine (2.3%) patients. Therapeutic failure was detected in six (1.5%), relapse occurred in four (1%), and persistent infertility related to brucellosis occurred in one patient. A localized scrotal infection in men or pyelonephritis in women in the absence of leucocytosis and with mild to moderate increases in inflammatory markers should signal the possibility of brucellar genitourinary disease.

Managing atypical and typical herpetic central nervous system infections: results of a multinational study

There have been many studies pertaining to the management of herpetic meningoencephalitis (HME), but the majority of them have focussed on virologically unconfirmed cases or included only small sample sizes. We have conducted a multicentre study aimed at providing management strategies for HME. Overall, 501 adult patients with PCR-proven HME were included retrospectively from 35 referral centres in 10 countries; 496 patients were found to be eligible for the analysis. Cerebrospinal fluid (CSF) analysis using a PCR assay yielded herpes simplex virus (HSV)-1 DNA in 351 patients (70.8%), HSV-2 DNA in 83 patients (16.7%) and undefined HSV DNA type in 62 patients (12.5%). A total of 379 patients (76.4%) had at least one of the specified characteristics of encephalitis, and we placed these patients into the encephalitis presentation group. The remaining 117 patients (23.6%) had none of these findings, and these patients were placed in the nonencephalitis presentation group. Abnormalities suggestive of encephalitis were detected in magnetic resonance imaging (MRI) in 83.9% of the patients and in electroencephalography (EEG) in 91.0% of patients in the encephalitis presentation group. In the nonencephalitis presentation group, MRI and EEG data were suggestive of encephalitis in 33.3 and 61.9% of patients, respectively. However, the concomitant use of MRI and EEG indicated encephalitis in 96.3 and 87.5% of the cases with and without encephalitic clinical presentation, respectively. Considering the subtle nature of HME, CSF HSV PCR, EEG and MRI data should be collected for all patients with a central nervous system infection.

Central nervous system infections in the absence of cerebrospinal fluid pleocytosis

Previous multicenter/multinational studies were evaluated to determine the frequency of the absence of cerebrospinal fluid pleocytosis in patients with central nervous system infections, as well as the clinical impact of this condition. It was found that 18% of neurosyphilis, 7.9% of herpetic meningoencephalitis, 3% of tuberculous meningitis, 1.7% of Brucella meningitis, and 0.2% of pneumococcal meningitis cases did not display cerebrospinal fluid pleocytosis. Most patients were not immunosuppressed. Patients without pleocytosis had a high rate of unfavorable outcomes and thus this condition should not be underestimated.

Tetanus in adults: results of the multicenter ID-IRI study

Tetanus is an acute, severe infection caused by a neurotoxin secreting bacterium. Various prognostic factors affecting mortality in tetanus patients have been described in the literature. In this study, we aimed to analyze the factors affecting mortality in hospitalized tetanus patients in a large case series. This retrospective multicenter study pooled data of tetanus patients from 25 medical centers. The hospitals participating in this study were the collaborating centers of the Infectious Diseases International Research Initiative (ID-IRI). Only adult patients over the age of 15 years with tetanus were included. The diagnosis of tetanus was made by the clinicians at the participant centers. Izmir Bozyaka Education and Research Hospital’s Review Board approved the study. Prognostic factors were analyzed by using the multivariate regression analysis method. In this study, 117 adult patients with tetanus were included. Of these, 79 (67.5%) patients survived and 38 (32.5%) patients died. Most of the deaths were observed in patients >60 years of age (60.5%). Generalized type of tetanus, presence of pain at the wound area, presence of generalized spasms, leukocytosis, high alanine aminotransferase (ALT) and C-reactive protein (CRP) values on admission, and the use of equine immunoglobulins in the treatment were found to be statistically associated with mortality (p < 0.05 for all). Here, we describe the prognostic factors for mortality in tetanus. Immunization seems to be the most critical point, considering the advanced age of our patients. A combination of laboratory and clinical parameters indicates mortality. Moreover, human immunoglobulins should be preferred over equine sera to increase survival.

The First Enterobacter cloacae Co-Producing NDM and OXA-48 Carbapenemases and Interhospital Spread of OXA-48 and NDM-Producing Klebsiella pneumoniae in Turkey

BACKGROUND The aim of this study was to investigate the occurrence of carbapenemase-producing Enterobacteriaceae. METHODS A total of 54 carbapenem nonsusceptible Enterobacteriaceae (CRE) isolates were recovered from clinical samples sent to the Dr. Lutfi Kirdar Kartal Training and Research Hospital from the period 2011 through 2014. Forty-four isolates were Klebsiella pneumoniae (CRKP) and the other 10 were Enterobacter cloacae (CREC).The isolate identifications and antibiotic sensitivity tests were performed using a Vitek2 automatic system. The clonality of isolates was determined using rep-PCR Diversilab. Presence of blaOXA-48, blaNDM, blaVIM, blaIMP, and blaKPC genes were screened using polymerase chain reaction (PCR) with specific primers. RESULTS CRKP were isolated from blood, urine, wounds, catheter tips, and tracheal aspirate samples; a total 44 isolates were evaluated. All isolates were nonsusceptible to ertapenem/imipenem or meropenem. Eighteen percent of the isolates were resistant to colistin. CREC were isolated from blood, urine, cerebrospinal fluid and sputum; a total of 10 isolates were evaluated. They were resistant to all carbapenems and 90% were resistant to cefoperazone/sulbactam and trimethoprim/sulfamethoxazole, and 50 - 70% isolates were resistant to gentamicin, amikacin, and ciprofloxacin. Thirty-three (75%) OXA-48 producing CRKP were identified. Thirteen (29.5%) were positive and two (4.5%) NDM-producing K. pneumoniae were co-producing OXA-48. Of the ten CREC strains tested, eight were positive for blaNDM, one isolate was positive for blaVIM and another for blaIMP genes. rep-PCR typing revealed the presence of a clonal dissemination in CRKP and CREC in the hospital. CONCLUSIONS To our knowledge, this is the first identification of blaNDM in E. cloacae isolates in Turkey. These findings describe an interhospital spread of CRKP-producing OXA-48 and NDM carbapenemases that started in 2011. Continuous monitoring is necessary to better understand their dissemination in the hospital, which probably occurred as a result of transmission from an environmental reservoir. These findings emphasize the need for intensive surveillance and precautions.

Risk factors for infection with colistin-resistant gram-negative microorganisms: a multicenter study.

BACKGROUND Knowing risk factors for colistin resistance is important since colistin is the only remaining choice for the treatment of infections caused by multi-drug resistant microorganisms. OBJECTIVE Evaluate risk factors associated with infection by colistin-resistant microorganisms. DESIGN Retrospective study. SETTINGS Tertiary healthcare centers. PATIENTS AND METHODS An e-mail including the title and purpose of the study was sent to 1500 infectious disease specialists via a scientific and social web portal named “Infeksiyon Dunyasi (Infection World)”. Demographic and clinical data was requested from respondents. MAIN OUTCOME MEASURE(S) Colistin-resistance. RESULTS Eighteen infectious disease specialists from twelve tertiary care centers responded to the invitation. Data was collected on 165 patients, 56 cases (39.9%) and 109 (66.0%) age- and sex-matched controls. The colistin-resistant microorganisms isolated from cases were 29 Acinetobacter baumannii (51.8%), 18 Pseudomonas aeruginosa (32.1%) and 9 Klebsiella spp. Colistin, carbapenem, and quinolone use in the last three months were risk factors for colistin resistance in the univariate analysis. Previous quinolone use in the last three months (P=.003; RR:3.2; 95% CI:1.5–6,7) and previous colistin use in the last three months (P=.001; RR: 3.6; 95% CI: 1.63–7.99) were significant risk factors in the multivariate analysis. CONCLUSION Clinicians should limit the use of quinolones and remain aware of the possibility of resistance developing during colistin use. LIMITATIONS The lack of a heteroresistance analysis on the isolates. No data on use of a loading dose or the use of colistin in combination.

Other Foci of Infections in Community Acquired Central Nervous System Infections

The data related to the distribution of other focal infections in central nervous system (CNS) infection patients is inconsistent in medical literature. Infectious Diseases International Research Initiative (ID-IRI) has been carrying on multicenter and multinational studies since 2008 and provided bulk of information on pneumococcal meningitis, brucellar meningitis, tuberculous meningitis, and herpetic meningoencephalitis as the largest case series in the literature. In this study, the databases of ID-IRI studies were reanalyzed and one fourth of pneumococcal and brucellar meningitis patients, and slightly less than half of tuberculous meningitis patients had another focal involvement out of CNS. Herpetic meningoencephalitis had only 7% coexistent other focal involvement. Consequently, the treating clinician should not undervalue the presence of another site of involvement in a CNS infection patient. Hence, diagnostic and therapeutic interventions for other site of involvement in due course of CNS infectious diseases should seriously be taken into consideration.

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.

Comparison of universal prophylaxis and preemptive approach for CMV associated outcome measures in renal transplant patients; a meta-analysis of available data

Cytomegalovirus (CMV) is a ubiquitous latent human virus that often causes complications in renal transplantation recipients. Universal prophylaxis and preemptive therapy are alternative strategies to prevent CMV associated complications. This meta‐analysis aimed to assess available data comparing the effectiveness of prophylaxis and preemptive therapy for preventing adverse outcomes. We searched the PubMed, Ovid, Web of Science, Cochrane Library, and Open Grey databases using a combination of keywords. Random effects models along with the Paule‐Mandel estimator were used to synthesize pooled effect estimates. Eleven studies were eligible for the final analysis. Universal prophylaxis was better at preventing CMV disease than the preemptive approach (risk difference = −0.0459; confidence intervals = −0.0791, −0.0127; P‐value = 0.0067; number needed to treat [NNT] = 22 [1/0.0459]; high, 79 [1/0.0127] patients; low, 13 [1/0.0791] patients). Subgroup analysis revealed a more consistent effect among studies published after 2010, with negligible between‐study heterogeneity. The NNT for universal prophylaxis to prevent one excess CMV disease concerning preemptive therapy was 16 (1/0.0630) patients (high, 25 [1/0.0394]; low, 12 [1/0.0867] patients) in the subgroup of studies performed after 2010. We detected no significant difference between the two strategies regarding acute rejection and graft loss, with negligible variability due to heterogeneity between studies. Although universal prophylaxis performed better than the preemptive strategy for the prevention of CMV disease, the high NNT value may discourage the use of CMV prophylaxis. Since there were no differences between the strategies concerning acute rejection and graft loss, this study supports the use of the preemptive approach as an alternative to universal prophylaxis.