[Generation of Antibiotic Tolerant Bacterial Persisters in Immunocompromized Patients with Hematologic and Malignant Diseases: A New Problem of Health-Care Associated Infections].

Background: Antibiotic tolerance (AT) represents one of the causes of the phenomenon of antibiotic resistance that allows escape of non-replicating metabolically inert microorganisms (persisters) from any antibiotics attack because molecular targets of antibiotics are lacking thereby creating the potential for chronic infections. Aims: Determine the heterogeneity of the strains of opportunistic pathogens E. coli and P. aeruginosa isolates from children with hematologic malignancies containing bacterial persisters that cause the AT phenomenon. Methods: Children with hematological malignancies were divided into 2 groups according to the intensity of antibiotic treatment of infectious complications. Ciprofloxacin-induced persisters were quantitatively determined in the biological materials obtained from sick children. Results: Within the clinical isolates of E. coli and P. aeruginosa, about a third of the strains belong to high-persisting. The numbers of persistent forms of bacteria did not correlate with a minimal inhibitory concentration values ciprofloxacin (r=0.148, n=25, p>0.05). Interestingly, higher level of formation of persistent E. coli and P. aeruginosa, is associated with higher frequencies of infection attacks, massive antibiotic use and unfavorable course of the disease in children. Conclusions: Therefore, detecting the persistent forms of bacterial pathogens including those associated with the health-care associated infection, specifically, in immunocompromised patients, should be included into the contemporary algorithms of microbiological observation and monitoring of patients and intrahospital environment.

[Factors influencing recovery in patients with hemoblastoses and candidemia].

UNLABELLED: aim: To study the factors influencing the results of treatment for candidemia (CE) in patients with blood system tumors. SUBJECTS AND METHODS: The investigation enrolled patients with hemoblastoses and CE. 30-day all-cause mortality was analyzed. RESULTS: In an 8-year period (2006-2013), CE was diagnosed in 55 patients (median age, 50 years); there was a preponderance of patients with lymphomas (47%) and acute leukemias (27%). The causative agents of CE were C. albicans (38%), C. parapsilosis (17%), C. krusei (11%), C. guilliermondii (11%), C. lusitaniae (6%), C. tropicalis (6%), C. glabrata (3%), C. famata (3%), C. pelliculosa (3%), and C. kefyr (2%). 30-day all-cause mortality was 43.6%. Recovery was statistically significantly more frequently seen following removal of a central venous catheter (67% versus 13%; p=0.004; odds ratio (OR), 14); after use of an antifungal drug on day 1 of isolation of Candida spp. from blood cultures (62% versus 13%; p=0.01; OR, 12); and that of echocandin as a first-line agent (86% versus 42%; p=0.005; OR, 8.4). The poor predictors were septic shock (5% recovery rate versus 86% in the patients without this factor; p<0.0001; OR, 0.01), granulocytopenia (42% versus 88%; p=0.001; OR, 0.1); use of amphotericin B as a first-line drug (26% versus 71%; p=0.002; OR, 0.15); hemoblastosis recurrence or resistance (39% versus 73%; p=0.01; OR, 0.24). Multivariate analysis showed the positive impact of antifungal administration on day 1 of isolation of Candida spp. from blood cultures on treatment results (p=0.03; OR, 27). CONCLUSION: High mortality rates were noted in the patients with hemoblastoses and CE. The recovery rates were statistically significantly higher after use of echinocandin as a first-line agent, after that of an antifungal agent on day 1 of positive blood cultures, after removal of a central venous catheter, and hemoblastosis remission.

[Viral mucosal lesions of the gastrointestinal tract organs in patients with lymphoma].

Infectious complications are one of the main causes of the lower efficiency of chemotherapy in hematologic oncology. The common infectious pathogens are herpes group viruses. The manifestations of herpesvirus infection or reactivation may be extremely diverse; just the same, digestive tract injury is rarely associated with herpesvirus infection in clinical practice. Viral mucosal injury of the intestine and pharynx is described in 2 patients with lymphomas during agranulocytosis. Virus-specific DNA was absent in blood; however, it was detected at high titers (the number of copies of 10(3) 10(5) genome-equivalent/mI) in feces and mucosal biopsy specimens. Addition of antiviral therapy could rapidly abolish infectious complications in both cases. Virological examination of material from the injury focus makes it possible to reveal a pathogenic virus even though the latter is undetectable in blood.

[Pneumocystis pneumonia in patients with Hodgkin lymphoma].

AIM: To assess the results of diagnosing and treating Pneumocystis pneumonia (PP) in patients with Hodgkin lymphoma (HL) over 15 years. SUBJECTS AND METHODS: In 1999 to 2013, PP occurred in 22 (3%) of 741 HL patients receiving programmed polychemotherapy (PCT). The male/female ratio was 1:1.1; median age was 32 (18-65) years. Advanced stages (IIB-IV) of the disease were seen in 82% of the patients. The diagnosis of PP was established when Pneumocystis (more than 5 cysts in the specimen) was detected in the lavage fluid by indirect immunofluorescence assay. RESULTS: PP developed after 4 or more cycles of PCT. Along with Pneumocystis, all the cases were found to have additional pathogens: herpes virus in 72% and bacteria and fungi in 33%. All the patients received combined antimicrobial therapy using high doses of intravenous trimethoprim-sulfamethoxazole. Ten (45%) patients required mechanical ventilation (MV). The total mortality in PP was 32% (7 patients died); moreover, none of the patients without MV died whereas the mortality among those who had MV was 70% (7 of the 10 patients died). High death rates (80%) were noted among the patients with recurrent and resistant HL. CONCLUSION: PP should be prevented with trimethoprim-sulfamethoxazole in patients with LH during PCT. If respiratory failure and X-ray signs of interstitial pneumonia appear, there is a need for fibrobronchoscopy with bronchoalveolar lavage and comprehensive microbiological testing of lavage fluid.

[Cryptococcosis in hematology practice].

AIM: To study the clinical manifestations of cryptococcosis, its diagnostic features, and treatment results in patients with hemoblastoses. SUBJECTS AND METHODS: The study included adult patients with cryptococcosis treated at the Hematology Research Center (HRC) in 2005 to 2011. The diagnosis of cryptococcosis was established on the basis of isolation of Cryptococcus neoformans from a blood culture or determination of positive cryptococcal antigen in the cerebrospinal fluid (CSF) of patients with infection symptoms. RESULTS: During 7 years, 19 patients aged 19 to 68 years (median 47 years) were diagnosed as having cryptococcosis. In the pattern of cryptococcosis, there was a preponderance of patients with lymphoma (31%) and those with acute lymphoblastic leukemia (26%) at the stages of hemoblastosis remission induction (32%) and consolidation (26%). The diagnosis was made in 9 (47%) patients at the Intensive Care Department, HRC. The major risk factors of cryptococcosis were previous cytostatic drug exposure (68%), use of immunosuppressive and glucocorticoid drugs (63%), and granulocytopenia (42%). Seventeen (78%) patients were diagnosed with cryptococcal meningitis or meningoencephalitis; 1 patient had cryptococcal sepsis and 1 patient had possible cryptococcal pneumonia. All the patients were given antifungal agents. Amphotericin B, fluconazole, and a combination of antimycotics were used as first-line drugs in 16 (84%), 1 (5.5%), and 2 (10.5%), respectively. When their health became better, the patients were treated with voriconazole or fluconazole. Within 30 days after the diagnosis of cryptococcosis, 5 (26%) patients died; of them 2 had tumor progression concurrent with infection. CONCLUSION: In cryptococcosis, the central nervous system is predominantly involved in the infectious process. The determination of cryptococcal antigen in CSF is a necessary diagnostic component in meningitis and meningoencephalitis in patients with blood system tumors, lymphatic ones in particular. When cryptococcosis is timely diagnosed and treated, its mortality, when the tumor is controlled, is lower than that in other invasive mycoses.

[Results of treatment for candidemia in patients with blood system tumors].

AIM: To study the etiology, clinical manifestations, risk factors, and results of treatment for candidemia (CE) in patients with blood system tumors. SUBJECTS AND METHODS: The investigation included the patients with CE and hemoblastoses treated at the Hematology Research Center, Ministry of Health of the Russian Federation, in 2006 to 2012. The diagnosis of CE was established according to the single isolation of Candida spp. from blood cultures and the presence of infection symptoms. RESULTS: Over 7 years, CE was diagnosed in 57 patients aged 17 to 77 years (median age 48 years). Among the patients with CE, there was a preponderance of those with lymphomas (54%) and acute leukemias (30%). The pathogens of CE were C. albicans (33%), C. guilliermondii (26%), C. parapsilosis (12%), C. krusei (8%), C. lusitaniae (5%), C. famata (4%), C. tropicalis (4%), C. glabrata (4%), and C. pelliculosa (4%). The major risk factors were polychemotherapy (85%), granulocytopenia (63%), mucosal Candida spp. colonization (82%), the presence of central venous catheter (CVC) (97%), antibiotics (100%), and glucocorticosteroids (70%). The infection occurred with the intake of an antifungal agent in 33% of the patients; 60% had concomitant infections of other etiology. Antifungal agents were given to 52 (91%) patients. Within 30 days after CE diagnosis, 20 (35%) patients died; of them 12 (60%) patients showed tumor progression concurrent with the infection. The cure rate for CE was significantly higher in the use of echinocandin as a first-line drug (92%), in complete or partial remission in hemoblastosis (90%), CVC removal (76%) and in the administration of an antifungal drug on day 1 of detection of positive blood cultures (75%). The cure rate was significantly lower when septic shock developed and a patient was transferred to an intensive care unit (15%), when amphotericin B was used as a first-line drug (45%), when granulocytopenia occurred (53%), or glucocorticoids were given (55%). CONCLUSION: Candida non-albicans constitute a high proportion among the pathogens of CE. A number of risk factors influencing survival rates in CE have been identified. It is crucial to use echinocandin as a first-line agent as soon as possible after isolation of Candida spp. from blood cultures.