Antimicrobial Resistance


Mechanisms of Resistance to Aminoglycosides in Gram-negative Nosocomial Bacteria in Russia: Results of Multicenter Study

G.K. Rechedko

Institute of Antimicrobial Chemotherapy, Smolensk State Medical Academy, Smolensk, Russia

The mechanisms of resistance to aminoglycoside antibiotics in Gram-negative nosocomial pathogens isolated in four Russian hospitals were studied. The most common and almost exclusive mechanism of aminoglycoside resistance was production of aminoglycoside-modifying enzymes. Various phenotypes of resistance were found. In Smolensk Regional Hospital the most common phenotype of resistance was gentamicin-tobramycin (54,4%, due to ANT(2'') enzyme) and gentamicin-tobramycin-netilmycin (36,1% – AAC(3)-V or combination of ANT(2'')+AAC(3)-Ia enzymes). The same phenotypes were predominant in Krasnodar Regional Hospital. In Central Clinical Hospital (Moscow) in addition to gentamicin-tobramycin (29,2%) and gentamicin-tobramycin-netilmycin (36,6%) phenotypes the cross-resistance to 2nd and 3rd aminoglycoside generations has been found: gentamicin-amikacin-isepamycin phenotype of resistance [due to combination of APH(3')-VI+AAC(3)-I enzymes] – in 4,9% of strains, gentamicin-tobramycin-amikacin-isepamycin phenotype [due to combination of APH(3')-VI+ANT(2'')] – in 9,8%, gentamicin-tobramycin-netilmycin-amikacin phenotype [due to combination of AAC(6')-I+ANT(2'') enzymes] – in 4,9%. In Main Military Clinical Hospital (Moscow) the following resistance phenotypes were detected: gentamicin-tobramycin [production of ANT(2'') enzyme] – 20,4%, gentamicin-tobramycin-netilmycin [AAC(3)-V or combination of ANT(2'')+AAC(6')-I enzymes] – 24,1%, gentamicin-tobramycin-netilmycin-amikacin-isepamycin [due to combination of APH(3')-VI+AAC(3)-V or APH(3')-VI+ANT(2'')+AAC(6')-I enzymes] – 12,9%, gentamicin-tobramycin-amikacin-isepamycin [due to combination of APH(3')-VI+ANT(2'') enzymes] – 25,9%, amikacin-isepamycin [APH(3')-VI enzyme] – 11,1%.

Key words: aminoglycosides, nosocomial infections, epidemiology, antimicrobial resistance.

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Antimicrobial Drug Use and Changes in Resistance in Streptococcus pneumoniae

Daniel J. Diekema, Angela B. Brueggemann, Gary V. Doern

University of Iowa College of Medicine, Iowa City, Iowa, USA

Translated and reprinted with permission from "Emerging Infectious Diseases" 2000; 6:552-6.

Resistance of Streptococcus pneumoniae to antimicrobial drug is increasing. To investigate the relationship between antimicrobial use and susceptibility of S.pneumoniae isolates at 24 U.S. medical centers, we obtained data on outpatient antimicrobial-drug use for the regions surrounding 23 of these centers. We found an association between decreased penicillin susceptibility and use of b-lactam antimicrobial drugs.

Key words: pneumococci, chemotherapy, antibiotic resistance, pharmacoepidemiology.

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Antimicrobial usage policy



Quality Measures of Antimicrobal Drug Use

Inge C. Gyssens

Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands

Translated and reprinted with permission from "International Journal of Antimicrobial Agents" 2001;17:9-19.


Antimicrobial use is the major determinant in the development of resistance. Many parameters of importance for optimal quality of antimicrobial therapy have already been defined. Maximal efficacy of the treatment should be combined with minimal toxicity at the lowest cost. Quality of antimicrobial drug use is dependent on knowledge of many aspects of infectious diseases. Considering efficacy, many of our indications for antimicrobial use need critical evaluation. Irrational use should be discouraged. Avoidance of the development of resistance is a quality parameter that will need increasing attention. This paper reviews the well.established factors that may influence the appropriateness of pharmacotherapy with antimicrobial drugs. It cites recent evidence supporting principles of prudent prescribing and gives an overview of audits that have addressed these parameters. Measures relating to resistance are discussed. All rights reserved.

Key words: antibiotics, antibiotic policy, antibiotic resistance, audit.

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Therapy of Exacerbation of Chronic Bronchitis in Ambulatory Practice: the Results of the Pharmacoepidemiological Study

S.N. Kozlov1, S.A. Ratchina1, N.P. Domnikova2, O.I. Karpov3, V.B. Kuzin4, I.V. Leschenko5, R.J. Likhatchova6, S.V. Nedogoda7, L.S. Stratchounski1

1 Institute of Antimicrobial Chemotherapy, Smolensk State Medical Academy, Russia
2 Novosibirsk State Medical Academy, Russia
3 Institute of Pharmacology, S.-Petersburg State Medical University named under I.P. Pavlov, Russia
4 Nizjni Novgorod State Medical Academy, Russia
5 Ekaterinburg Clinical Hospital N 33, Ekaterinburg, Russia
6 Oupatient department N 7, Moscow, Russia
7 Volgograd State Medical Academy, Russia


Case histories of outpatients with acute exacerbation of chronic bronchitis (AECB) were analyzed. Diagnoses were classified according to the ICD-10, antimicrobials – to the ATC classification. Altogether 783 case histories of patients aged from 16 to 92 (average age 51,6+13,7) were included in the study.

The most frequently prescribed group of medications were antimicrobials for systemic use (83,9%), cough and cold preparations (75,5%), bronchodilators (48,7%), antihistamines (23,0%) and vitamins (9,7%). The most common antimicrobial prescribed was co-trimoxazole (31,8%), followed by ciprofloxacin (16,4%), ampicillin (14,5%) and gentamσcin (10,0%). For antimicrobial treatment monotherapy was used in 84,8% of cases, combination of 2–3 antibiotics – in 15,2% of patients. Average duration of antimicrobial therapy was 8,2+3,4 days. The most common bronchodilators prescribed were preparations of theophylline (76,1%), M-anticholinergic agents (15,4%) and complex ephedrine-containing medications (14,9%).

This study has shown unacceptably high rate of inappropriate approach to the therapy of AECB: irrational choice of antibacterials, use of archaic and potentially toxic drugs, wide use of medications with non-proven clinical efficacy.

Key words: exacerbation of chronic bronchitis, antimicrobial therapy, pharmacoepidemiology.

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Laboratory Diagnostics



Rapid Phenotypic Methods for the Detection of Diphtheria Toxin Amongst Clinical Isolates of Corynebacteria

K.H. Engler1, D. Norn2, R.S. Kozlov3, I. Selga4, T.G. Glushkevich5, M. Tam2, R.C. George1, A. Efstratiou1

1 PHLS Central Public Health Laboratory, London, UK;
2 Programme for Appropriate Technology in Health (PATH), Seattle, USA;
3 Institute of Antimicrobial Chemotherapy, Smolensk, Russia;
4 National Environmental Health Centre, Ministry of Welfare, Riga, Latvia;
5 Ukrainian Centre of National Sanitary and Epidemiological Surveillance, Kiev, Ukraine


Two rapid, phenotypic methods were developed for the detection of diphtheria toxin amongst clinical isolates of corynebacteria, an enzyme immunoassay (EIA) and an immunochromatographic strip (ICS) test. Both assays use equine polyclonal antitoxin as the capture antibody. The detecting antibody is a monoclonal antibody, specific for fragment A of the diphtheria toxin molecule, labelled with alkaline phosphatase for use in the EIA and colloidal gold for the ICS. The assays are rapid, sensitive and specific: a final result is available within 3h of colony selection and toxigenicity can be detected from isolates grown on a diverse range of culture media, including selective agars. The limits of detection of the EIA are 0,1 ng/ml and of the ICS test 0,5 ng/ml diphtheria toxin.

Toxin detection using the EIA was compared to the Elek test and PCR detection of fragment A of the diphtheria toxin (tox) gene, using 245 isolates of corynebacteria. The results for the EIA were in complete concordance with the Elek test: 87 toxigenic and 158 non-toxigenic isolates. Ten of the phenotypically non-toxigenic strains were found to contain fragment A of the tox gene but did not express the toxin protein. These isolates were found to be non-toxigenic in the Vero cell tissue culture cytotoxicity assay and were therefore, non-toxi-genic for diagnostic purposes. The use of the ICS test, in comparison with the Elek test, for detection of toxigenicity was evaluated in field trials in countries of the former USSR, using 488 isolates of various Corynebacterium spp. The results for the ICS test were in complete concordance with the Elek test (243 toxigenic and 245 non-toxigenic isolates). The ICS test was also evaluated for direct detection of toxigenicity from throat swabs. One hundred and twelve throat swabs from suspected diphtheria cases and carriers were examined by conventional culture and direct ICS. The results showed 98% concordance (110/112) and the sensitivity and specificity of the ICS was 95 and 99%, respectively.

Key words: diphtheria, diphtheria toxin, Corynebacterium spp., laboratory diagnostics.

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Guidelines for clinicians



Practice Guidelines for the Management of Infectious Diarrhea

According to the guidelines of Infectious Diseases Society of America
(R.L. Guerrant, T.V. Gilder, T.S. Steiner, N.M. Thielman, L. Slutsker, R.V. Tauxe, T. Hennessy, P.M. Griffin, H. DuPont, R. Bradley Sack, P. Tarr, M. Neill, I. Nachamkin, L. Barth Reller, M.T. Osterholm, M.L. Bennish, L.K. Pickering. Practice guidelines for the management of infectious diarrhea. Clin Infect Dis 2001; 32:331-50.)

Yu.V. Lobzin, S.B. Yakushin, S.M. Zakharenko

Academy of Military Medicine, S.-Petersburg, Russia

There is increasing recognition of a widening array of enteric patogens associated with illnesses of the gastrointestinal tract. Along with well-known microorganisms – Salmonella, Shigella and rotaviruses, agents such as enterohemorrhagic E.coli, Cyclospora, Cryptosporidium, Giardia, Campylobacter jejuni, Clostridium difficile, caliciviruses and other enteric virus patogens are increasing cause of acute diarrheal illnesses. Critical to development a cost-effective approach to the evaluation and management of infectious diarrhea is the selective use of available diagnostic methods, therapies, and preventive measures. This article reviews the recommendations that address following: oral rehydration, clinical and epidemiological evaluation, perfomance of selective fecal studies, administration of selective antimicrobial therapy, contradicted antidiarrheals, and available immunizations. This document indicates, which patients to test, what tests are more effective, what medical treatment to use, and what steps to take to ensure that appropriate public health actions are implemented.

Key words: infectious diarrhea, enteric infections, stool culture, antimicrobial chemotherapy.

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Guidelines for microbiologists



Detection of Extended Spectrum b-lactamases by Phenotypic Methods in Gram-negative Bacteria

Production of extended-spectrum b-lactamases (ESBL) is the one of most widespread and clinically significant mechanism of resistance to modern b-lactams in members of the family Enterobacteriaceae. But the effectiveness of routine methods of antimicrobial susceptibility testing for detection of ESBL production remains extremely low. In connection with this the recommendations for use of special phenotypic methods with their advantages and limitations for detection of ESBL are described.

This guidelines are designed for microbiologists, epidemiologists, and laboratory assistants.

Key words: b-lactamases, ESBL, Gram-negative bacteria, microbiological diagnostics, antimicrobial resistance.

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Working experience



Microbiological Diagnosis of Opportunistic Vaginal Infections

A.S. Ankirskaya, V.V. Muravyeva

Research Center of Obstetrics, Gynecology and Perinatology of Russian Academy of Medical Sciences, Moscow, Russia

Criteria for the evaluation of vaginal biocenosis developed in the Research Center of Obstetrics, Gynecology and Perinatology of the Russian Academy of Medical Sciences (Moscow, Russia) are presented. According to these criteria the microbiological diagnostic of opportunistic vaginal infections includes: 1) exclusion of the STDs, 2) Gram stain of vaginal smear (vaginal epithelium, leucocytes and microorganisms are evaluated), 3) culture of vaginal discharge. Criteria for normal biocenosis, bacterial vaginosis, vaginal candidosis, non-specific vaginitis, vaginal atrophy are given.

Key words: gynecology, vaginosis, vaginitis, vaginal candidosis, microbiological diagnostic.

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