Poster Session VI

Various
(P 67 - P 81)

P 67

FREQUENCY AND SENSITIVITY PATTERN OF EXTENDED SPECTRUM BETA LACTAMASE PRODUCING ISOLATES IN A TERTIARY CARE HOSPITAL LABORATORY OF PAKISTAN

K. Saleh
Aga Khan University, Pakistan

Objective: To determine frequency, distribution and sensitivity pattern of EBSL producing organism at a tertiary care hospital laboratory in Pakistan.

Methods: All Enterobacteriaceae isolated in a tertiary care hospital laboratory between April and August 2002 were studied. Isolates were speciated according to standard biochemical tests. Susceptibility testing was performed by Kirby-Bauer disk diffusion method. ESBL detection was done through a double disk method using cefotaxime (30 µg) versus cefotaxime plus clavulanate (30+10 µg) according to NCCLS. Statistical analysis was through SPSS version 10. Tests of significance were calculated using chi-square test.

Results: During the 6 months study period 1137/2840 (40%) of the isolates tested were found to be ESBL producing. ESBL positivity was detected in 50% of Enterobacter, 41% of E. coli and 36% of K. pneumoniae tested. ESBL production was noted in 52% of nosocomial isolates tested (415/799). In terms of age distribution, ESBL was more frequent in patients at the extremes of ages (under 5 years and more than 60 years). Furthermore cross-resistance to non-beta lactam antibiotics (fluoroquinolones, aminoglycosides and co-trimoxazole) was also more frequent in ESBL producing organisms (p value < 0.05).

Conclusion: We document a high prevalence of ESBL positivity amongst our isolates. Several laboratories in developing countries do not routinely detect ESBL production. However, our data supports an urgent need for regular screening and surveillance for these organisms. Cross resistance to non-beta-lactams agents is alarming particularly in low-income settings where expensive second line agents are unavailable. Control of increasing antimicrobial resistance should be included in national health policies as a matter of priority.

P 68

INCIDENTAL INTRATHECAL INFUSION OF CEFOTIAM: A CASE REPORT

G. Brössner, K. Engelhardt, R. Beer, B. Pfausler, A. Georgopoulos, E. Schmutzhard
Department of Neurology, University Hospital, Innsbruck,
Department of Internal Medicine I, Division of Infectious Diseases and Chemotherapy, University of Vienna, Austria

We report the case of a 66-year-old man with a carcinoma of unknown primary (CUP), suffering from disseminated bone, pulmonary and extramedullar intradural metastases, who was admitted to the neuro intensive care unit because of massive myocloni, spasticity of all extremities, signs and symptoms of secondary rhabdomyolysis and increasing respiratory failure. This lifethreatening condition most likely was triggered by an incidental intrathecal infusion of Cefotiam (approximately 1.5 g) into an intradurally placed catheter of a pain management system via an external pump. The level of Cefotiam in the cerebrospinal fluid was 198.8 µg/ml (day 2) and 10.1 µg/ml (day 5). Neuroradiological (magnetic resonance images) and neurophysiological work up (somatosensory and motor evoked potentials) did not reveal any severe structural or functional lesions which could have been attributed to the intrathecal Cefotiam application. The therapeutic critical care interventions (mechanical ventilation and hemofiltration) and monitoring of vital parameters had to be continued for 2 weeks. Several weaning attempts – within the first 10 days – had to be stopped due to immediate reappearance of severe myocloni. After a total of three weeks intensive care management and monitoring the patient could be discharged from the NICU, the neurological status having returned to the previous condition. To the best of our knowledge, we present the first case of an incidental intrathecal administration of Cefotiam, showing a distinct neurological syndrome with myocloni and secondary rhabdomyolysis, having been successfully treated by aggressive intensive care measures.

P 69

PLASMA CONCENTRATIONS OF TUMOR NECROSIS FACTOR ALPHA, INTERLEUKIN-1A AND ERYTHROPOIETIN AND THEIR RELATIONDSHIP WITH CLINICAL OUCOME IN PATIENT WHO UNDERWENT SURGICAL INTERVENTION

S.O. Kosulnikov, V.I. Lulko
Department of Hospital Surgery, Dnipropetrovsky State Medical Academy, Dniepropetrovsk, Ukraine

The problem of pathogenesis and treatment of sepsis, septic shock, multiorgan insufficiency are discussed. The result of clinical examination and treatment of 31 patients with gastrointestinal stoma are presented. In 27 cases the stoma was removed by an abdominal intervention. The investigation employed enzyme immunoassay. Enteroanastomosis was carried out by double-row suture and drainage of area of the anastomosis from the perineum site by tubes for prevention of the development of peritonitis even in case of insufficiency of the anastomosis was made. Complications developed in 12.3% of patients, letality made up 9.8%. Plasma cytokine concentrations fluctuate in serious illness. We conclude that both plasma TNF-alpha and IL-1alpha concentration often increase in sepsis and following operative trauma. Elevated level of interleukin 1-alpha (IL-1alpha IT and tumor necrosis factor have been increased significantly in patients before death.
The mean erythropoietin production in serum of patients was 31.17 pg/ml compared with a control of 6.07 pg/ml. It’s shown that optimal pathogenetic control of the inflammatory process is possible by means of modulation of cytokine effect and depend from individualize basal plasma levels. The level of TNF-alpha and IL-1alpha may to be used as a marker of prognosis for life in patients with multiorgan insufficiency individualize.

P 70

IDENTIFICATION OF A NEW PORE-FORMING OUTER MEMBRANE PROTEIN IN ACINETOBACTER BAUMANNII.

A. Siroy, E. Dé, D. Seyer, P. Cosette, M. Pestel-Caron, D. Vallenet, C. Lemaître-Guillier, A. Van Dorsselaer, T. Jouenne
Université de Rouen, Mont-St-Aignan, Faculté de Médecine et de Pharmacie, Rouen
Génoscope, Centre National de Séquençage, Evry, Université Louis Pasteur, Strasbourg, France

Acinetobacter baumannii is an ubiquitous gram-negative coccobacillus which is an important cause of nosocomial infections in hospitals. From 1999 to 2001, multiresistant strains were isolated during outbreaks in the emergency unit of the hospital of Rouen (France). At this time, little is known about multidrug resistance of A. baumannii. These resistances might imply some alterations of the cell wall permeability. Consequently, we investigated the outer membrane protein pattern of a standard strain of A. baumannii (ATCC19606) as a prelude to the study of an imipenem resistant clinical isolate. In a first step, extraction of the bacterial cell wall and separation of the inner from the outer membrane were performed by ultracentrifugation on a sucrose gradient. In a second step, we analysed by SDS and 2D-PAGE the proteic content of the outer membrane and identified two major proteins by mass spectrometry and N-terminal sequencing: the HMP porin and a 29 kDa protein which had been already involved in the imipenem resistant of another clinical isolate. Trypsic digests of this 29 kDa protein allowed us to obtain peptidic sequences by MALDI-TOF/TOF. By comparison with databases, no homology was found with known membrane proteins. Purification of this protein, using SDS-PAGE followed by electroelution in a Triton X-100 medium, allowed us to perform functional studies: reconstitution in planar lipid bilayers demonstrated ion-channel forming properties for this 29 kDa protein.

P 71

INVASION OF BACTERIA OF THE RESPIRATORY TRACT IN EPITHELIAL CELLS

C. Kratzer, W. Graninger, A. Georgopoulos
Dept. of Infectious Diseases and Chemotherapy, General Hospital, University of Vienna, Austria

Objective: In the present study, invasiveness of 10 group A beta-hemolytic streptococci (GAS) and 7 nontypeable Haemophili influenzae (NTHI) were analyzed.

Methods: All tested bacteria were clinical isolates from patients with respiratory infections. As epithelial cells, NHBE (human normal bronchial epithelial cells) of Clonetics and HNEpC-p (human nasal epithelial cells) of PromoCell were used. The uptake of bacteria in epithelial cells was evaluated by quantifying the number of viable intracellular bacteria recovered from epithelial cells at the end of a standard antibiotic protection assay called internalizing or invasion assay.

Results: Six of the ten tested GAS throat isolates had the ability to invade HNEpC-p cells, but they didn’t exhibit high invasion efficiency.
Sensitive NTHI showed a total different distribution in invasiveness in comparison to the beta-lactamase-positive isolates. Resistant haemophili achieved an obvious higher bacterial count within the bronchial epithelial cells than the sensitive bacteria.

Conclusion: For group A beta-hemolytic streptococci, no difference in the distribution of intracellular sensitive and macrolide antibiotics-resistant strains was found. For nontypeable Haemophilus influenzae, it could be shown that beta-lactamase-positive NTHI achieved good invasion in bronchial epithelial cells, whereas sensitive strains weren’t invasive at all or exhibited only low invasiveness.

P 72

RECOMBINANT ALLERGENS PROMOTE EXPRESSION OF CD203c

A.W. Hauswirth, P. Valent
University of Vienna, Austria

Traditionally, the diagnosis of type I allergies is based on clinical data, skin tests, and laboratory tests employing allergen extracts. During the past few years several attempts have been made to refine diagnostic assays in clinical allergy by introducing recombinant allergens and novel markers of IgE-dependent cell activation. We have identified the ectoenzyme CD203c as a novel basophil antigen that is upregulated on IgE-receptor cross-linkage. In this study, we applied CD203c and a panel of recombinant allergens to establish a novel basophil-test that allows for a reliable quantification of IgE-dependent responses at the effector cell level. Patients allergic to birch (Bet v 1, n=15; Bet v 2, n=8) and grass (Phl p 1, n=15; Phl p 2, n=10; Phl p 5, n=14) pollen allergens as well as 10 non-allergic donors were examined. Basophils were exposed to various concentrations of recombinant allergens for 15 minutes and then examined for expression of CD203c by flow cytometry. CD203c upregulation was correlated with the increase in CD63.
Exposure to recombinant allergens resulted in a dose-dependent increase in expression of CD203c on peripheral blood basophils in sensitized individuals, whereas no increase was seen in healthy controls. The effects of the recombinant allergens on CD203c expression were also time-dependent. There was a good correlation between allergen-induced upregulation of CD203c and upregulation of CD63 (R=0.76).
Flow cytometric quantitation of CD203c on blood basophils exposed to recombinant allergens is a useful approach to determine the allergic state in sensitized individuals and represents a basis for a sensitive novel allergo-test.

P 73

FUNCTIONAL AND MORPHOLOGIC CHARACTERIZATION OF DAY-10 GRANULOCYTES IN AML PATIENTS PATIENTS RECEIVING HIDAC OR IDAC FOR CONSOLIDATION

M.T. Krauth, S. Florian, A.W. Hauswirth, P. Samorapoompichit, W.R. Sperr, P. Valent
Dept. of Internal Medicine I, Div. of Hematology & Hemostaseology, University of Vienna, Austria

High dose- (HiDAC) and intermediate dose- (IDAC) ARA-C have recently been introduced as effective post remission treatment for pts with acute myeloid leukemia (AML). These regimens have been reported as a safe approach with a relatively low rate of infections and a relatively short time of absolute neutropenia. In this study, we analyzed the numbers, phenotype, and functional properties of neutrophils in AML pts during consolidation with HiDAC (n=6) or IDAC (n=6). We found that the absolute numbers of neutrophils (ANC) remained at relatively high levels until day 10-14. In a majority of the pts, the ANC on day 10/11 were > 500/5l. These cells were found to be mature neutrophils by Wright-Giemsa staining and electron microscopy (EM). They contained secondary granules, phagosomes, and lysosomes similar to neutrophils in healthy controls. In addition, these cells exhibited oxidative burst activity as assessed by the NBT test, and expressed phagocytosis-related and activation-linked cell surface antigens including the C3biR (CD11b), CR1 (CD35), C5aR (CD88), FcgRI (CD64), FcgRII (CD32), FcgRIII (CD16), G-CSF-R (CD114), GM-CSF-Ra (CD116), and sLx (CD15). The biologic significance of neutrophils persisting until day 10 in AML pts was confirmed in functional analyses using fluorescence labeled, heat-killed E. coli bacteria, flow cytometry, and electron microscopy. In these experiments, day 10 neutrophils were found to take up bacteria into phagolysosomes in the same way as neutrophils in healthy controls. In summary, our data show that considerable numbers of functionally active neutrophils survive until day 10 in AML pts treated with HiDAC or IDAC. The consecutive delay in neutropenia may be responsible for the relatively low rate of severe infections in these pts compared to other regimens employing high dose ARA-C in combination with other cytostatic drugs.

P 74

TREATING AN INFECTED ROTATING-HINGE ARTHROPLASTY BY A SALVAGE TOTAL KNEE REVISION PROCEDURE – A CASE REPORT

E. Georgopoulou, D. Kafidas, I.C. Vossinakis, L.S. Badras
Orthopaedic Department, General Hospital of Volos, Greece

Aim: To present a complex case of infection complicating total knee replacement.

Case Report: A 75-year-old, obese woman with severe bilateral knee osteoarthritis was subjected in December 1999 to a total knee arthroplasty on her left knee.
A constrained prothesis was used due to severe deformity. This rotating-hinge device required an extensile bone resection.
Wound dehiscence occurred, requiring reclosure.
On the 9th postoperative month she presented an established infection along with a draining sinus. Culture swabs from the discharge grew enterococcus sensitive to amoxicilline/clavulanic acid. Clinical signs and infection markers responded well to a 3-month IV antimicrobial treatment, which continued orally for another 4 months.
In April 2001 recurrence occurred. 5 months later the prothesis was removed and an external fixator applied. A new strain of multiresistant enterococcus was isolated from tissue specimens, requiring IV teicoplanine for another 3 months. Wound healing progressed uneventfully and the fixator was substituted by a functional knee brace.
In June 2002 revision surgery was performed, using the same type of prothesis.
No further complications occurred so far.
Management of infection following joint replacement surgery can be quite challenging.

P 75

PROCALCITONIN AS A MARKER IN BACTERIAL INFECTIOUS DISEASE DIAGNOSIS

S. Iacob, I. Rebedea, A. Cristescu, M. Ioan, M. Pana
Matei Bals Institute of Infectious Diseases, Bucharest, Romania
Cantacuzino Institute

Objective: To assess the value of procalcitonin (PCT) detection in rapid diagnosis of different types of infections.

Methods: Retrospective study of patients with systemic inflammatory response syndrome (SIRS) of bacterial etiology, admitted in Matei Bals Infectious Diseases Institute (Bucharest), from a period of 2 years (2000-2002).
The diagnoses were based on clinical examination and paraclinical parameters (haematologic, biochemic, and radiologic examination). Bacterial etiology was confirmed in all patients (positive culture of specific samples). The serum level of PCT was measured using BRAHMS PCT-Q test in the first 10 days of illness, before antibiotherapy.

Results: 153 patients from a total group of 230 patients with documented SIRS were confirmed with bacterial infections (97 patients with localized infections, 45 patients with systemic infections).The range of PCT plasma concentrations in respect to different bacterial infections was analyzed (tabel).

Conclusion: In the recent years serum PCT measurement was recommended as a possible marker of generalized and severe infections. In our study serum PCT determination was also helpful in localized bacterial infections (62% positivity) predominantly in severe cases (83% positivity). All the patients with clinical forms of tuberculosis had negative PCT.

  Diagnosis
No. of
patients
No. of patients
with positive PCT
range of serum PCT
(ng/ml)
  Localized infections
  1. Bacterial pneumonia
      Severe forms of pneumonia
27
9
21
9
0.5-10 or >10
0.5-10 or >10
  2. Bacterial meningitis
      Severe forms of meningitis
27
6
21
3
2-10 or >10
> 10
  3. Bacterial pyelonephritis
20
12
> 10
  4. Streptococcus pharyngitis
20
8
> 0.5
  5. Staphylococcus cellulitis
3
2
> 0.5
  6. Pulmonary tuberculosis
5
0
< 0.5
  7. Tuberculous meningitis
6
0
< 0.5
  Systemic infections
  8. Bacterial endocarditis
      Severe forms of endocarditis
30
6
11
2
0.5-10 or 10
> 10
  9. Sepsis
      Severe forms of sepsis
15
12
9
6
0.5-10 or >10
0.5-10 or >10

P 76

INHIBITION OF PRO- AND EUKARYOTIC TOPOISOMERASE II DNA-CLEAVAGE MEDIATED BY MOXIFLOXACIN

B. Körber, P. Heisig
Pharmaceutical Biology and Microbiology, University of Hamburg, Germany

Introduction: The bactericidal effect of fluoroquinolones results in lethal double stranded DNA-breaks caused by stabilising bacterial type II topoisomerase-DNA-cleavage-complexes. Due to the enhanced clinical application of fluoroquinolone drugs and the similarities in mechanism and structure of pro- and eukaryotic topoisomerases II we studied the selectivities of two modern fluoroquinolones for these enzymes by analyzing their abilities to stabilize pro- and eukaryotic cleavage complexes. Ciprofloxacin served as a reference.

Methods: Fluoroquinolone mediated inhibition of prokaryotic E. coli gyrase and eukaryotic human topoisomerase II cleavage reaction was carried out by using a new cleavage assay protocol. DNA-cleavage was determined as the minimum amount of moxifloxacin (MXF), gatifloxacin (GTX) and – as a reference – ciprofloxacin (CPX) to induce visible cleavage (i.e. 10% = CC10) of substrate DNA.

Results: The CC10 values of gyrase were 0.01 µg/ml, 0.05 µg/ml, and 0.005 µg/ml for MXF, GTX, and CIP, respectively. The CC10 values of human topo II were 6 µg/ml, 2 µg/ml, and 10 µg/ml for MXF, GTX, and CIP, respectively.

Conclusion: Cleavage data indicate that the fluoroquinolones tested showed drug-specific selectivity for bacterial gyrase: MXF is 600fold and GTX 40fold more effective in stabilizing cleavage complexes with E. coli gyrase than with human topo II, compared to CIP (2000fold).

P 77

AMPLIFYING ANTIMICROBIAL ACTION OF ANTIBIOTICS WITH THE USE OF PROTEOLYTIC INHIBITOR AMBEN

A.S. Fedchuk, Y.A. Boschenko, V.A. Pushkina, V.P. Lozitsky, N.N. Man’kovskaya
I.I. Mechnikov Ukrainian Research Anti-Plague Institute, Odessa, Ukraine

Background: Tularemia could be used as the infectious agent during bioterroristic attack. Cholera is treated traditionally also as the dangerous emerging disease. The scope of the present work is the study of the para-aminomethyl benzoic acid (Amben) influence on the sensitivity of Francisella tularensis and Vibrio cholerae to different antibiotics.

Methods: We have studied the antimicrobial action of 14 representatives of 10 antibiotics’ classes combined with Amben. Antimicrobial susceptibility test was performed by the disk diffusion method. Ft-agar contained 1% of Amben. Strains of Vibrio cholerae: cholerae: strain 569 (VCC 569), El-Tor strain 754 (VCEl 754), Non-01 strain 146/11 (VCNon-01 146/11) and virulent strain 29 of Francisella tularensis were used.

Results: We have discovered that all studied infectious agents are resistant to Amben action taken apart from antibiotics. Amben increased antimicrobial activity of gentamicin and syzomycin against of all studied strains of Vibrio cholerae. It has enhanced anti-cholera action of: i) cefotaxim, ofloxacin and lomefloxacin to VCC 569 and VCNon-01146/11; ii) kanamycin - to VCC 569 and VCEl 754; iii) norfloxacin - to VCEl 754 and VCNon 01 146/11.
Amben increased antimicrobial action of some researched antibiotics against one strain of Vibrio cholerae. Amben enhanced also anti-tularemia activity of tetracyclin.

Conclusion: Analysis of the results has shown that proteolysis inhibitor Amben increase antimicrobial efficacy of different classes of antibiotics against various strains of Francisella tularensis and Vibrio cholerae. Our research has shown also that Amben could be added in certain dosage to the antibiotics while treating the infections studied.

P 78

INVESTIGATION ON IN VITRO ANTIMICROBIAL ACTIVITY OF TWO BASIC SALTS OF ZINC AND COPPER AND THEIR EFFECTS ON VIABILITY AND PROLIFERATION OF VIRUS-TRANSFORMED CELLS

R. Alexandrova, T. Popova, Y. Martinova, M. Gabrashanska, S. Tepavitcharova
Institute of Experimental Pathology and Parasitology, BAS, 25 Acad. G. Bonchev Str, Sofia 1113, Bulgaria; Faculty of Veterinary Medicine, Forest Technical University, IEMA, IGIC, BAS, Bulgaria

The aim of the present study was to investigate the in vitro antimicrobial properties
of two basic salts of zinc and copper [Zn5-xCux(OH)8Cl2.H2O and CuCO3Cu(OH)2.nH2O] and their effects on viability and proliferation of virus-transformed cells. The antimicrobial potential was studied on 48 gram-positive and gram-negative bacterial strains by the routine agar-diffusion method of Bauer-Kirby and the method of minimum inhibitory concentrations (MIC). Both salts exhibited antimicrobial activity in vitro although the established MICs were higher than these of gentamicin. The cytotoxic and antiproliferative effects of the compounds on LSR-SF-SR (established from a transplantable sarcoma in rat induced by Rous sarcoma virus strain Schmidt-Ruppin) and LSCC-SF-MC29 (obtained from a transplantable chicken hepatoma induced by myelocytomatosis virus Mc29) cell lines were evaluated. The influence on cell viability was investigated by neutral red uptake cytotoxicity test. The antiproliferative properties were studied using colony-forming assay and autoradiography. CuCO3Cu(OH)2.nH2O possessed more pronounced cytotoxic and antiproliferative potential than Zn5-xCux(OH)8Cl2.H2O. This salt inhibited the colony-forming ability of both cell lines at concentrations > 0.1 mg/ml. When applied in dose 0.1 mg/ml the compound decreased the number of LSR-SF-SR and LSCC-SF-Mc29 labeled cells with 35% and 43%, respectively.

P 79

ACTIVITY OF DISSOLVED MITOMYCIN C AFTER DIFFERENT METHODS OF LONG-TIME STORAGE

M. Georgopoulos, C. Vass, Z. Vatanparast, C. Pahr, A. Georgopoulos
Ophthalmology, University of Vienna, Austria

Purpose: The cytostatic substance Mitomycin C (MMC) is used in trabeculectomy to enhance the success rate in problematic cases and is usually dissolved immediately before application, but only about 1% of the substance is needed for treatment. We evaluated different methods of long-time storage of MMC over a period of 6 months.

Methods: MMC (Kyowa) in concentrations of 0.05, 0.1, 0.2, and 0.4 mg/ml is prepared at the local pharmaceutical department and stored at room temperature (20-24°C), at 4°C (refrigerator), at -20°C (freezer compartment) and at -196°C (liquid N2). The activity of MMC is evaluated with bioassays after 30 minutes, 1, 3, 7, 14, 30, 90 and 180 days for the different concentrations and storage methods.

Results: There was no difference in the long-term stability of the investigated MMC concentrations. 90% of the initial activity was preserved after storage for 1 week at room temperature, 1 month at -20°C or 3 months at 4°C. At 6 months the activities were 16%, 48%, and 78% of the initial values.

Conclusion: MMC can be stored in solution for use in trabeculectomy in the refrigerator for up to 3 months without significant loss of activity. Storage at room temperature is not recommended. Costs of trabeculectomy can be reduced by storage of reconstituted solutions rather than dissolving MMC before each glaucoma-surgery.

P 80

LINEZOLID IN COMBINATION WITH VANCOMYCIN AND TEICOPLANIN AGAINST MRSA BY SPECTROPHOTOMETRIC OPTICAL DENSITY MEASUREMENTS

N. Geisler, R. Gattringer, W. Graninger, A. Georgopoulos
Department of Internal Medicine I, Division of Infectious Diseases and Chemotherapy, University of Vienna, Vienna, Austria

Objective: The Checkerboard method to assess antimicrobial combinations is based on linear dose-response curves and therefore on the FIC (fractional inhibitory concentration) of the tested antimicrobial agents. Using a spectrophotometric method for synergy experiments is a more appropriate way, because it considers not only non-linear dose response curves, but also shows a more kinetic view of the tested antimicrobial combination.

Methods: In these studies we used the BIOSCREEN C Analyzer to measure the effects of antimicrobial combinations on the growth rate constant of 5 strains of MRSA. Growth rate constants were calculated from plots of the logarithm of the optical density (OD) versus time. The growth rate constant is defined by OD(t) = OD(0)egt. The effects of antimicrobial combinations were assessed using increasing concentrations of one drug plus a fixed concentration of the other drug which leads to a 50% reduction in the value of g compared with the control value of g (in the absence of antimicrobial agents). The results were plotted in diagrams by using a logarithmic scale of drug concentration on the x-axis and the percent reduction of growth rate constant on the y-axis. We tested Linezolid in combination with Teicoplanin and Vancomycin, once increasing concentrations of Linezolid combined with a fixed concentration of either Teicoplanin or Vancomycin and then the converse experiment, with varied concentrations of Teicoplanin/Vancomycin and a fixed concentration of Linezolid.

Results: Increasing concentrations of Teicoplanin and an intermediate concentration of Linezolid showed synergy, but Linezolid combined with the IC50 of Teicoplanin produced an autonomous or slight additive response. Vancomycin produced an antagonistic response when combined with Linezolid. The results were better with the fixed concentration of Vancomycin, but showed a large variability.

Conclusion: The combination of Linezolid with Teicoplanin and its once a day or even three times a week administration might be an interesting alternative treatment of chronic osteomyelitis or endocarditis. Another advantage would be the possibility of outpatient therapy to save costs and prevent the spread of resistant strains throughout the hospital during a long stay.

P 81

IN VITRO ACTIVITY OF GATIFLOXACIN AND SEVEN OTHER ANTIBIOTICS AGAINST RESPIRATORY AND URINARY TRACT PATHOGENS FROM THE COMMUNITY - FIRST RESULTS OF THE BASIC-STUDY

H. Grimm
On Behalf of an European Multicenter Study Group, Institute of Medical Microbiology, Weingarten, Germany

Objectives: To obtain present figures on resistance against gatifloxacin and other antibiotics.

Methods: A total of 23 centers in Austria, Belgium, France, Germany, Italy, Portugal, Spain and Switzerland are involved in the BASIC study (Bacterial Annual Susceptibility Information Collection). The MICs of gatifloxacin (Gati), ciprofloxacin (Cipro), clarithromycin (Clari), benzylpenicillin G (Pen), amoxicillin (Amox), amoxicillin/clavulanic acid (Coamox), cefuroxime (Cur) and cefixime (Cix) were determined using the microdilution method. Each center is requested to investigate about 30 strains each of the following species: S. pneumoniae (Spn), S. pyogenes (Spy), S. aureus (Sau), E. faecalis (Efa), M. catarrhalis (Mca), H. influenzae (Hin), E. coli (Eco), K. pneumoniae (Kpn), P. mirabilis (Pmi) and P. aeruginosa (Pae).

Results: In 2001 and 2002 altogether 5,462 strains are enrolled. Despite of any exceptions per regions some important MIC90% / percentage susceptible were as follows:
*) NCCLS breakpoints not available

 
n
Gati
Cipro
Clari
Coamox
Cur-axetil
  Spn
558
0.5 / 98.9
2 / - *)
Ž64 / 67.7
1 / 98.0
4 / 79.4
  Hin
580
0.03 / 100
0.03 / 99.8
16 / 86.0
1 / 95.3
2 / 94.8
  Mca
361
0.06 / 100
0.06 / 99.7
0.5 / 99.2
0.25 / 98.9
2 / 97.8
  Sau
589
2 / 92.0
16 / 80.5
64 / 68.1
16 / 86.1
64 / 86.8
  Eco
670
2 / 91.3
1 / 90.0
64 / - *)
16 / 75.2
8 / 95.2
  Pmi
563
4 / 88.6
2 / 89.0
64 / - *)
16 / 87.6
32 / 85.6
  Pae
569
16 / 72.1
16 / 76.3
64 / - *)
16 / - *)
64 / - *)

Conclusion: From the oral antibiotics tested gatifloxacin has the highest activity and broadest spectrum against all relevant respiratory and urinary tract pathogens. Gatifloxacin is a promising alternative for therapy of respiratory and urinary tract bacterial infections.

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