TABLE OF CONTENT

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1. ANTIMICROBIAL ACTIVITY OF DAPTOMYCIN - A NEW ANTIBIOTIC TESTED AGAINST METHICILLIN-RESISTANT STAPHYLOCOCCI AND VANCOMYCIN-RESISTANT ENTEROCOCCI ISOLATED IN DIFFERENT BULGARIAN MEDICAL CENTERS

Tz. Velinov, M. Petrov, V. Dimitrova, S. Velikova, T. Kantardjiev

ABSTRACT
Daptomycin is a cyclic lipopeptide with potent activity and broad spectrum against Gram-positive bacteria currently used for the treatment of complicated skin and skin structure infections and bacteremia, including right sided endocarditis. We evaluated the in vitro activity of this compound against clinical strains of staphylococci and enterococci collected from Bulgarian medical centers in the National Reference Laboratory for „Control and Monitoring of Antimicrobial Resistance“ at the NCIPD.

A total of 100 non-duplicate clinical strains from different medical centers were tested for susceptibility by reference agar microdilution methods according to Clinical and Laboratory Standards Institute guidelines and interpretative criteria.

All S. aureus strains were inhibited at a daptomycin MIC of <1 mg/L. Among tested E. faecium strains the highest daptomycin MIC value was 2 mg/L (MIC50 under 0.5 mg/L), while among E. faecalis and E. avium the highest MIC value was 1 mg/L. Daptomycin showed excellent in vitro activity against staphylococci and enterococci collected in the National Reference Laboratory for „Control and Monitoring of Antimicrobial Resistance“ and appears to be an excellent therapeutic option for serious infections caused by methicillin-resistant staphylococci and vancomycin-resistant enterococci.


2. IMMUNE RECOVERY OF HIV+ PATIENTS WITH DIFFERENT BASELINE CD4 ABSOLUTE COUNTS AFTER 24 MONTHS OF HIGHLY ACTIVE ANTIRETROVIRAL THERAPY

G. Albarki, M. Nikolova, M. Muhtarova, A. Mihova, K. Kostov, D. Beshkov, H. Taskov

ABSTRACT
Human immunodeficiency virus (HIV) infection leads almost inevitably to progressing immune deficiency. Timely administration of highly active antiretroviral therapy (HAART) decreases viral load (VL) and permits the preservation and partial restoration of the CD4 T cell pool. Although CD4 absolute counts (CD4 AC) between 200 and 350 cells/pl are accepted as a paramount criterion for starting HAART, choosing the right time has proved a complicated issue. In order to set variables predictive for an effective response to therapy, we monitored the changes in CD4AC, VL and CD38 quantitative expression (CD38 ABC) on CD8 T cells in the course of 24 months of HAART in treatment-nanve HIV+ patients (average CD4 AC 115 cells/pl, range 2 - 431 cells/pl), sub grouped according to baseline CD4 counts. At the endpoint, patients were retrospectively classified according to the effect of HAART into: responders (sustained immunologic and virologic response), transient responders (transient/absent immunologic and virologic response) and paradox responders (immunologic response combined with ongoing HIV replication). According to our results, the effect of HAART was independent from baseline CD4 counts. Our data provide strong evidence that baseline CD4 cell count alone cannot predict the effect of therapy in patients with advanced HIV infection and CD4 AC < 400 cells/pl. Considering other parameters such as CD38ABC might be helpful.


3. BK-POLYOMAVIRUS (BKV) EXCRETION AND VIREMIA IN WOMEN WITH PRIMARY AND RECURRENT GYNECOLOGICAL MALIGNANCIES

Sv. Slavov, A. Gancheva, A. Petrova, Zl. Kalvatchev

ABSTRACT
Reactivation of latent viral infections is one of the major causes for morbidity and mortality among patients with cancer. Human polyomavirus BK (BKV) causes latent infection and is frequently reactivated in immunocompromised hosts. Apart from patients with leukemic malignancies, the disease pattern among individuals with other types of oncologic diseases is not investigated. We examined 109 women with tumors of the genitalia separated into two groups: with primary neoplasia and a group receiving diverse kinds of therapeutic procedures. Both groups had high and similar values of BKV urine reactivation, over 60%, and a small percentage (>10%) of viremia. We imply that the general immune dysfunction caused by the tumor itself, rather than therapeutic approach is a major factor for BK viral reactivation in this group of patients.


4. OCCURRENCE OF MULTIRESISTANT ENTEROBACTER CLOACAE STRAIN IN A NEUROSURGERY INTENSIVE CARE UNIT

H. Hitkova, V. Popova, E. Kanjovska, M. Sredkova, R. Vatcheva, K. Lubenova, N. Rangeiov

ABSTRACT
From May to July 2007, multi-resistant E. cloacae were isolated from tracheal aspirates of three patients admitted to the neurosurgery intensive care unit at University Hospital - Pleven. These isolates were resistant to broad-spectrum cephalosporins, gentamicin and tobramycin, and susceptible to cefepime, carbapenems and quinolones. On the basis of that, an outbreak was suspected and an epidemiological study was performed. Susceptibility results showed circulation of hospital acquired strain E. cloacae resistant to extended-spectrum cephalosporins. Further molecular typing is required to determine whether a limited spread of a single strain existed and to recognize the exact types of resistance. Epidemiological data didn,t confirm outbreak and revealed colonization of respiratory tract in patients involved. Multi-resistant E. cloacae were cultured from the aspirating catheter solutions, so that the environmental sources of such isolates were determined and effective control measures were established. Despite of that, occurrence of multi-resistant E. cloacae in an intensive care unit is a great risk for emerging nosocomial infections.


5. COMBINED TREATMENT OF HYDATIDOSIS WITH ALBENDAZOLE AND AN IMMUNO-STIMULATOR ISOPRINOSINE

D. Vutchev, I. Marinova, R. Harizanov, V. Blagoeva, A. Massarlieva, K. Anichina, A. Mavrova

ABSTRACT
Immuno-suppression accompanies hydatidosis in humans. The non-specific immuno-stimulator Isoprinosine and albendazole were administered to three groups of patients: post surgery, post PAIR and as conservative therapy. Evidence accumulated during the 2-5 year follow-up show that Isoprinosine is an effective supplementary treatment in patients with lung and liver hydatidosis.


6. TOWARDS MORE OPTIMAL ANTIMICROBIAL THERAPY OF PYELONEPHRITIS: PERIODIC AUDIT FOLLOWED BY ONE YEAR ANALYSIS

E. Keuleyan, P. Yovchevski, T. Anakieva, V. Mladenova, R. Hristov, N. Lazov

ABSTRACT
An audit of antibiotic prescriptions is a contemporary tool in the assessment of antibiotic policies. The objective of this work is to analyze the antimicrobial treatment of pyelonephritis in 2005 at Nephrology Ward of our hospital following analysis and feedback from 3-month audits undertaken 2003,2004, and 2005. Appropriateness of treatment was assessed with regard to microbiology results, clinical outcome, adherence to hospital antibiotic policy and national guidelines. Among 106 patients with pyelonephritis, the most frequent pathogens in community acquired uncomplicated pyelonephritis (CAUP) were: Escherichia coli - 67.9%, Klebsiella spp -11.5%, Enterococci 5.7%. In complicated pyelonephritis (CP) the etiology included: E. coli - 36.7%, Pseudomonas spp - 27.3%, microbial associations of two uropathogens -31.1%, from: Enterococcus, Enterobacter, Proteus, Klebsiella, Candida spp. Typically, for the treatment of CAUP, I.V. f luoroquinolon (FQ) for 2-10 days (d) was sequenced to P.O. FQ for 0-8 d, - 39.8%; the other choices represented: aminoglycosides - 28.2%; broad-spectrum cephalosporins -19.2%, amoxicillin/clavulanate - 8.9%, others - 3.9%. For empiric therapy of CP and/or hospital-acquired pyelonephritis (HAP), I.V. FQ or aminoglycosides were prescribed (in absence of specific reasons for another medication). Antimicrobial combinations were used in uro-sepsis or in haemodynamic instability - 4.7 %. While in most cases of CAUP favorable results were obtained, the management of CP and HAP was a challenge due to antibiotic resistance to the first and second line antibiotics and underlying disease. Emergence of ESBL among Enterobacteriaceae (7 patients) and polyresistance in P. aeruginosa, incl. penems (4 patients) was of special concern. The successful treatment needed combined effective antimicrobial therapy and management of abnormalities, in conclusion, the antibiotic therapy of pyelonephritis was evaluated as appropriate, due to good clinical and microbiological results, accepted conclusions from the previous audits, and adherence to the hospital guidelines. The problems seen were related to the emerging antimicrobial resistance (use of reserve and expensive antibiotics) and the managing of complicating conditions.


7. CHARACTERIZATION OF CONJUGATIVE PLASMIDS MEDIATING THE DISSEMINATION OF 16S RIBOSOMAL RNA METHYLASES RESPONSIBLE FOR PANAMINOGLYCOSIDE RESISTANCE OF CLINICAL ENTEROBACTERIACEAE IN A BULGARIAN CANCER HOSPITAL

S. Sabtcheva, T. Kantardjiev, M. Kaku

ABSTRACT
During 2004-2005, high-level resistance to aminoglycosides due to 16S ribosomal RNA methylation was identified in 20 strains of the family Enterobacteriaceae, including Klebsiella pneumoniae, Escherichia coli, Citrobacter freundii, Enterobacter cloacae, Serratia marcescens and Klebsiella oxytoca, at the cancer center of Sofia. The ArmA methylase-mediated aminoglycoside resistance was transferable by conjugation and carried by IncLM plasmids ranging in size from ca. 80.6 to 99.3 kilobase pairs. In addition, all ArmA plasmids carried the following genes: blaCTX-M-3 (extended-spectrum beta-lactam resistance), blaTEM-1, (ampicillin resistance), ant3“9 (streptomycin-spectinomycin resistance), aac3-ll (gentamicin-tobramycin-netilmicin-kanamycin resistance), dfrXIl (trimethoprim resistance), sul1 (sulfonamide resistance) and intH, an integrase associated with class 1 integrons. We conclude that ArmA-mediated panaminoglycoside resistance was disseminated across various species in the family Enterobacteriaceae by closely related, broad-host-range IncLM conjugative plasmids, which conferred similar multidrug resistance phenotypes.


8. PLASMID-MEDIATED PER-1 EXTENDED-SPECTRUM BETA-LACTAMASE IN PROVIDENCIA RETTGERI FROM BULGARIA

S. Sabtcheva, T. Kantardjiev, E. Georgieva, S. Panaiotov, M. Kaku

ABSTRACT
A multiresistant Providencia rettgeri strain was isolated from the urine of a 38-year-old female cancer patient during an episode of febrile neutropenia that followed a course of postoperative adjuvant chemotherapy. The strain was resistant to beta-lactams (except cephamycins and carbapenems), aminoglycosides, fluoroquinolones, chloramphenicol, tetracycline, trimethoprim and sulfonamides. Clavuianic acid restored activity of oxyimino-cephalosporins, suggesting the production of an extended-spectrum beta-lactamase (ESBL). PCR and sequencing with primers specific for known ESBL genes identified blaPER-1. The PER-1 determinant was transferable by conjugation and cotransferred with blaTEM-1 (ampicillin resistance), aac(6’)-lb (amikacin-tobramycin-kanamycin resistance), gentamicin, chloramphenicol, trimethoprim and sulfonamide resistance determinants. Plasmid-mediated quinolone resistance determinants (qnr and aac(6’)-lb-cr) were not detected. This is the first description of plasmid-mediated PER-1 enzyme in Enterobacteriaceae in Bulgaria. Since PER-1 -positive Gram-negative pathogens have been increasingly isolated in Turkey and Europe, and given the potential for further dissemination, nationwide early recognition and rapid identification of PER-1 -producing bacteria should be considered to avoid further spread of this resistance determinant.


9. CLINICAL THERAPY AND CHEMOPROPHYLAXIS OF TRICHINOSIS WITH BENZIMIDAZOLES

D. Vutchev, K. Eneva, K. Anichina, V. Blagoeva, A. Mavrova

ABSTRACT
Etiological treatment of trichinosis was possible in the last 2-3 decades due to the synthesis and administration of benzimidazole derivatives. Thiabendazole, mebendazole, flubendazole and albendazole were introduced consecutively in clincal practice. Accumulated evidence proved that medendazole and flubendazole are effective in the intestinal stage of trichinosis. Albendazole is effective during intestinal infection and to some extent during the tissue stage. Thiabendazole is no longer used in clinical practice due to its significant adverse reactions. Early diagnosis of trichinosis and epidemiological surveillance identifies patients at risk. Adequate chemoprophylaxis prevents further expansion of the outbreak.


 

Editor-in-Chief
Prof. B. Petrunov, MD, DSc

Production Manager
Theodor Koshev

Editorial Board
Prof. H. Taskov, MD, DSc
Prof. P. Nenkov, MD, DSc
Assoc. Prof. R. Kurdova, MD, PhD
Assoc. Prof. R. Kotzeva, MD, PhD
Assoc. Prof. N. Gatcheva, MD, PhD
Assoc. Prof. T. Kantardjiev, MD, PhD

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