Ilker Inanc Balkan

Monotherapy versus combination therapy for sepsis due to multidrug-resistant Acinetobacter baumannii: analysis of a multicentre prospective cohort

BACKGROUND Treatment of multidrug-resistant Acinetobacter baumannii (MDRAB) infection presents a challenge because of the scarcity of available options. Even though combination therapy (CT) is frequently used in clinical practice, data are needed to support its use instead of monotherapy (MT). METHODS A prospective observational study was conducted in 28 Spanish hospitals. Patients with sepsis caused by MDRAB, defined according to strict criteria, and who received active antibiotic treatment (according to in vitro susceptibility testing) for at least 48 h, were included. The main outcome variable was all-cause 30 day mortality after initiation of targeted therapy. Multivariate analysis, including a propensity score (for receiving CT), was performed by Cox regression. RESULTS One hundred and one patients were included in the analysis; 68 (67.3%) received MT and 33 (32.7%) received CT. Pneumonia was the most common infection (50.5%), 68.6% of cases being associated with mechanical ventilation. Colistin (67.6%) and carbapenems (14.7%) were the most common drugs used in MT; colistin plus tigecycline (27.3%) and carbapenem plus tigecycline (12.1%) were the most frequent combinations. Crude 30 day mortality was 23.5% and 24.2% for the MT and CT groups, respectively (RR = 1.03; 95% CI 0.49-2.16; P = 0.94). Multivariate analysis of 30 day survival showed no trend towards reduced 30 day mortality with CT (HR = 1.35; 95% CI 0.53-3.44; P = 0.53). Subgroup analysis showed similar results. CONCLUSIONS Our data do not support an association of CT with reduced mortality in MDRAB infections. More data for specific types of infection and combinations are needed.

Blood stream infections due to OXA-48-like carbapenemase-producing Enterobacteriaceae: treatment and survival

BACKGROUND Blood stream infections (BSIs) due to carbapenem-resistant Enterobacteriaceae (CRE) are associated with high hospital mortality rates and present a tremendous challenge to clinicians. The optimal treatment remains undefined. We aimed to investigate the risk factors for mortality and the correlation between different treatment modalities and outcomes. METHODS The clinical characteristics and treatment outcomes of a cohort of 36 patients with BSIs due to CRE were investigated and a retrospective nested case-control study of surviving and non-surviving patients was conducted. RESULTS Fifty percent of the cases were male and the mean patient age was 54.9 ± 15.8 years. Klebsiella pneumoniae was the etiological agent in 26 cases (72.2%), Escherichia coli in eight (22.2%), and Enterobacter aerogenes in two (5.5%). All strains were phenotypically positive for carbapenemase activity and all except two (one E. coli and one K. pneumoniae) yielded both blaOXA-48 carbapenemases and blaCTX-M-type extended-spectrum beta-lactamases (ESBLs) in PCR products. The 14-day, 28-day, and all-cause in-hospital mortality rates were 41.6%, 50%, and 58.3%, respectively. The median time to death was 8 days (range 2-52 days). No significant differences were observed between survivors and non-survivors in terms of baseline characteristics, comorbid conditions, etiologies, or sources of bacteremia, however hematological malignancies (p=0.015) and prolonged neutropenia (p=0.044) were more common in non-survivors. Microbiological eradication and clinical response within 7 days were two major determinants of 28-day attributable mortality (p=0.001 and p=0.001, adjusted r(2)=0.845). Colistin-based dual combinations, and preferably triple combinations, were associated with significantly better outcomes when compared to non-colistin-based regimens (p<0.001). Time to active treatment had a significant effect on the course of infection (p=0.014). CONCLUSION Earlier active treatment with colistin based regimens and microbiological and clinical response within 7 days are major predictors of survival in cases of BSIs due to CRE. Rectal screening offers the advantage of earlier recognition and prompt empirical treatment.

Colistin nephrotoxicity increases with age.

Abstract Background: Colistin (COL) has become the backbone of the treatment of infections due to extensively drug-resistant (XDR) Gram-negative bacteria. The most common restriction to its use is acute kidney injury (AKI). Methods: We conducted a retrospective cohort study to evaluate risk factors for new-onset AKI in patients receiving COL. The cohort consisted of 198 adults admitted to 9 referral hospitals between January 2010 and October 2012 and treated with intravenous COL for ≥ 72 h. Patients with no pre-existing kidney dysfunction were compared in terms of risk factors and outcomes of AKI graded according to the RIFLE criteria. Logistic regression analysis was used to identify associated risk factors. Results: A total of 198 patients met the inclusion criteria, of whom 167 had no pre-existing kidney dysfunction; the mean patient age was 58.77 (± 18.98) y. Bloodstream infections (34.8%) and ventilator-associated pneumonia (32.3%) were the 2 most common indications for COL use. New-onset AKI developed in 46.1% of the patients, graded as risk (10%), injury (15%), and failure (21%). Patients with high Charlson co-morbidity index (CCI) scores (p = 0.001) and comparatively low initial glomerular filtration rate (GFR) estimations (p < 0.001) were more likely to develop AKI, but older age (p = 0.001; odds ratio 5.199, 95% confidence interval 2.684–10.072) was the major predictor in the multivariate analysis. In-hospital recovery from AKI occurred in 58.1%, within a median of 7 days. Conclusions: COL-induced nephrotoxicity occurred significantly more often in patients older than 60 y of age and was related to low initial GFR estimations and high CCI scores, which were basically determined by age.

Mortality indicators in pneumococcal meningitis: therapeutic implications

BACKGROUND The aim of this study was to delineate mortality indicators in pneumococcal meningitis with special emphasis on therapeutic implications. METHODS This retrospective, multicenter cohort study involved a 15-year period (1998-2012). Culture-positive cases (n=306) were included solely from 38 centers. RESULTS Fifty-eight patients received ceftriaxone plus vancomycin empirically. The rest were given a third-generation cephalosporin alone. Overall, 246 (79.1%) isolates were found to be penicillin-susceptible, 38 (12.2%) strains were penicillin-resistant, and 22 (7.1%) were oxacillin-resistant (without further minimum inhibitory concentration testing for penicillin). Being a critical case (odds ratio (OR) 7.089, 95% confidence interval (CI) 3.230-15.557) and age over 50 years (OR 3.908, 95% CI 1.820-8.390) were independent predictors of mortality, while infection with a penicillin-susceptible isolate (OR 0.441, 95% CI 0.195-0.996) was found to be protective. Empirical vancomycin use did not provide significant benefit (OR 2.159, 95% CI 0.949-4.912). CONCLUSIONS Ceftriaxone alone is not adequate in the management of pneumococcal meningitis due to penicillin-resistant pneumococci, which is a major concern worldwide. Although vancomycin showed a trend towards improving the prognosis of pneumococcal meningitis, significant correlation in statistical terms could not be established in this study. Thus, further studies are needed for the optimization of pneumococcal meningitis treatment.

The Syrian conflict and infectious diseases

ABSTRACT The conflict in Syria is a big humanitarian emergency. More than 200,000 Syrians have been killed, with more than half of the population either having been displaced or having immigrated. Healthcare has been interrupted due to the destruction of facilities, a lack of medical staff, and a critical shortage of life-saving medications. It produced suitable conditions leading to the re-emergence of tuberculosis, cutaneous leishmaniasis, polio, and measles. Lebanon and Jordan reported increased rates of tuberculosis among Syrian refugees. Cutaneous leishmaniasis outbreaks were noted not only in Syria but also in Turkey, Jordan, and Lebanon. After a polio-free 15 years, Syria reported a polio outbreak. Ongoing measles outbreaks in the region was accelerated by the conflict. Iraq declared a cholera outbreak among the Syrian refugees. The healthcare facilities of the countries hosting immigrants, mainly Turkey, Lebanon, Jordan, Iraq, and Egypt, are overburdened. The majority of the immigrants live in crowded and unsanitary conditions. Infectious diseases are big challenges for Syria and for the countries hosting immigrants. More structured support from international organizations is needed for the prevention, control, diagnosis, and treatment of infectious diseases.

Comparison of community‐onset healthcare‐associated and hospital‐acquired urinary infections caused by extended‐spectrum beta‐lactamase‐producing Escherichia coli and antimicrobial activities

We aimed to compare community‐onset healthcare‐associated (CO‐HCA) and hospital‐acquired (HA) urinary tract infections (UTIs) caused by extended‐spectrum beta‐lactamase (ESBL)‐producing Escherichia coli in terms of epidemiology, clinical outcomes and antimicrobial activities.

Epidemiology of HBV subgenotypes D

The natural history of hepatitis B virus infection is not uniform and affected from several factors including, HBV genotype. Genotype D is a widely distributed genotype. Among genotype D, several subgenotypes differentiate epidemiologically and probably clinically. D1 is predominant in Middle East and North Africa, and characterized by early HBeAg seroconversion and low viral load. D2 is seen in Albania, Turkey, Brazil, western India, Lebanon, and Serbia. D3 was reported from Serbia, western India, and Indonesia. It is a predominant subgenotype in injection drug use-related acute HBV infections in Europe and Canada. D4 is relatively rare and reported from Haiti, Russia and Baltic region, Brazil, Kenya, Morocco and Rwanda. Subgenotype D5 seems to be common in Eastern India. D6 has been reported as a rare subgenotype from Indonesia, Kenya, Russia and Baltic region. D7 is the main genotype in Morocco and Tunisia. D8 and D9 are recently described subgenotypes and reported from Niger and India, respectively. Subgenotypes of genotype D may have clinical and/or viral differences. More subgenotype studies are required to conclude on subgenotype and its clinical/viral characteristics.

The Changing Epidemiology of Bloodstream Infections and Resistance in Hematopoietic Stem Cell Transplantation Recipients

Objective: Patients receiving hematopoietic stem cell transplantation (HSCT) are exposed to highly immunosuppressive conditions and bloodstream infections (BSIs) are one of the most common major complications within this period. Our aim, in this study, was to evaluate the epidemiology of BSIs in these patients retrospectively. Materials and Methods: The epidemiological properties of 312 patients with HSCT were retrospectively evaluated. Results: A total of 312 patients, followed between 2000 and 2011, who underwent autologous (62%) and allogeneic (38%) HSCT were included in the study. The most common underlying malignancies were multiple myeloma (28%) and Hodgkin lymphoma (21.5%). A total of 142 (45%) patients developed at least 1 episode of BSI and 193 separate pathogens were isolated from the blood cultures. There was a trend of increase in the numbers of BSIs in 2005-2008 and a relative increase in the proportion of gram-positive infections in recent years (2009-2011), and central venous catheter-related BSI was found to be most common source. Coagulase-negative staphylococci (49.2%) and Acinetobacter baumannii (8.8%) were the most common pathogens. Extended-spectrum beta-lactamase-producing strains were 23% and 22% among Escherichia coli and Klebsiella spp. isolates, respectively. Quinolone resistance was detected in 10% of Enterobacteriaceae. Resistance to carbapenems was not detected in Enterobacteriaceae, while it was seen at 11.1% and 23.5% in Pseudomonas and Acinetobacter strains, respectively. Conclusion: A shift was detected from gram-negative bacteria to gram-positive in the etiology over the years and central lines were the most common sources of BSIs.

The course of spinal tuberculosis (Pott disease): results of the multinational, multicentre Backbone-2 study

We aimed to describe clinical, laboratory, diagnostic and therapeutic features of spinal tuberculosis (ST), also known as Pott disease. A total of 314 patients with ST from 35 centres in Turkey, Egypt, Albania and Greece were included. Median duration from initial symptoms to the time of diagnosis was 78 days. The most common complications presented before diagnosis were abscesses (69%), neurologic deficits (40%), spinal instability (21%) and spinal deformity (16%). Lumbar (56%), thoracic (49%) and thoracolumbar (13%) vertebrae were the most commonly involved sites of infection. Although 51% of the patients had multiple levels of vertebral involvement, 8% had noncontiguous involvement of multiple vertebral bodies. The causative agent was identified in 41% of cases. Histopathologic examination was performed in 200 patients (64%), and 74% were consistent with tuberculosis. Medical treatment alone was implemented in 103 patients (33%), while 211 patients (67%) underwent diagnostic and/or therapeutic surgical intervention. Ten percent of the patients required more than one surgical intervention. Mortality occurred in 7 patients (2%), and 77 (25%) developed sequelae. The distribution of the posttreatment sequelae were as follows: 11% kyphosis, 6% Gibbus deformity, 5% scoliosis, 5% paraparesis, 5% paraplegia and 4% loss of sensation. Older age, presence of neurologic deficit and spinal deformity were predictors of unfavourable outcome. ST results in significant morbidity as a result of its insidious course and delayed diagnosis because of diagnostic and therapeutic challenges. ST should be considered in the differential diagnosis of patients with vertebral osteomyelitis, especially in tuberculosis-endemic regions. Early establishment of definitive aetiologic diagnosis and appropriate treatment are of paramount importance to prevent development of sequelae.

Acute generalized exanthematous pustulosis after ceftriaxone use resembling sepsis

Acute generalized exanthematous pustulosis is an uncommon disorder, characterized by the acute onset of multiple pruritic, small, nonfollicular, sterile, superficial pustules over erythematous and edematous skin. It is frequently caused by medications, mainly antibiotics, and particularly beta-lactams. It is a rare condition that is not well known in infectious disease practice. We report a case of ceftriaxone-induced acute generalized exanthematous pustulosis that presented with the appearance of sepsis. After discontinuation of ceftriaxone, the findings were improved.