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D Milatovic

Publications and source records attributed to D Milatovic.

At least 55 records · Page 3Linked to original sources
PubMed1999

Molecular epidemiology of quinolone resistance and comparative in vitro activities of new quinolones against European Staphylococcus aureus isolates.

UNLABELLED: New fluoroquinolones (FQ) may possibly be used as alternative therapeutic options for Staphylococcus aureus infections. Our objectives were: (1) to define the in vitro activities of seven FQs in a collection of 434 methicillin-susceptible and 457 methicillin-resistant S. aureus from 23 European university hospitals; (2) to characterise the prevalence of mutations in the grlA and gyrA genes in all ciprofloxacin-resistant (n=433) isolates of S. aureus; (3) to determine the percentage of ciprofloxacin-resistant S. aureus strains with measurable quinolone efflux. METHODS: (1) The in vitro activities of different FQs were determined by microdilution tests. (2) PCR-amplified DNA was sequenced. (3) Ciprofloxacin minimum inhibitory concentrations (MIC) were determined in the presence and absence of reserpine, which inhibits efflux pumps. RESULTS: (1) Irrespective of the methicillin resistance of the isolates, sitafloxacin and clinafloxacin showed the best in vitro activities. (2) All ciprofloxacin-resistant isolates exhibited GrlA alterations, namely Ser-80-->Phe or Tyr or Glu-84-->Lys or Ala-116-->Glu or Pro or a combination of Ser-80-->Phe and Glu-84-->Val. These alterations in GrlA were combined with alterations in GyrA, namely Ser-84-->Leu or Lys or Glu-88-->Lys or Val. (3) Reserpine reduced ciprofloxacin MIC values in ca. 30% of the clinical isolates tested. CONCLUSIONS: (1) This current European overview of mutations involved in FQ resistance demonstrates that only a limited number of classical mutations in grlA and gyrA contributed to resistance in clinical isolates. (2) An efflux pump is involved in ca. 30% of ciprofloxacin-resistant S. aureus isolates. (3) Sitafloxacin and clinafloxacin are two very promising new FQs with good anti-staphylococcal activity. New FQs, perhaps in combination with efflux pump inhibitors, might play a role in the treatment of S. aureus infections.

Anti-Infective Agents↗
PubMed1999

Association of alterations in ParC and GyrA proteins with resistance of clinical isolates of Enterococcus faecium to nine different fluoroquinolones.

The parC and gyrA genes of 73 ciprofloxacin-resistant and 6 ciprofloxacin-susceptible Enterococcus faecium clinical isolates were partly sequenced. Alterations in ParC and GyrA, possibly in combination with other resistance mechanisms, severely restricted the in vitro activities of the nine quinolones tested. For all isolates, clinafloxacin and sitafloxacin showed the best activities.

Anti-Infective Agents↗
PubMed1999

Comparative in vitro activities of ciprofloxacin, clinafloxacin, gatifloxacin, levofloxacin, moxifloxacin, and trovafloxacin against Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, and Enterobacter aerogenes clinical isolates with alterations in GyrA and ParC proteins.

The in vitro activities of ciprofloxacin, clinafloxacin, gatifloxacin, levofloxacin, moxifloxacin, and trovafloxacin were tested against 72 ciprofloxacin-resistant and 28 ciprofloxacin-susceptible isolates of Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, and Enterobacter aerogenes. Irrespective of the alterations in GyrA and ParC proteins, clinafloxacin exhibited greater activity than all other fluoroquinolones tested against K. pneumoniae and E. aerogenes.

Anti-Infective Agents↗
PubMed1998

Azithromycin versus cefaclor in the treatment of pediatric patients with acute group A beta-hemolytic streptococcal tonsillopharyngitis.

An open, comparative multicenter study was performed to evaluate the efficacy and safety of azithromycin (10 mg/kg) given once daily for three days in comparison with cefaclor (30 mg/kg) divided into three daily doses and given for a period of ten days. One hundred and twenty-two children aged 1-12 years with clinical symptoms of group A beta-hemolytic streptococcal tonsillopharyngitis and a positive throat culture were randomly allocated to the treatment groups. Overall, the clinical success (cure or improvement) of both regimens was identical in the evaluable patients (86.3%, 44 of 51 patients in either treatment group). In contrast, bacterial eradication after completion of treatment was lower with azithromycin than with cefaclor. Possible reasons for this discrepancy between clinical success and eradication rates could be antibiotic resistance, pre-disease carriage or insufficient dosage. Both agents were well tolerated; only mild or moderate side effects most frequently involving the gastrointestinal tract, were recorded in either therapy group.

Anti-Bacterial Agents↗
PubMed1998

[Use of mechanical autotransfusion in maxillofacial surgery in the mouth, jaw and face].

OBJECTIVE: In maxillofacial surgery considerable blood loss is not uncommon. However, the use of autologous blood collected from the site of surgery is controversial. METHODS: Bacterial contamination of blood collected for autologous retransfusion was studied by standard microbiological methods in 25 patients undergoing elective non-malignant maxillofacial surgery. Swabs were taken from the pharynx and from the collected blood before and after routine treatment. The autologous blood was not used for transfusion. Preoperative antibiotic treatment consisted in amoxicilline plus clavulanic acid. RESULTS: The blood prepared for retransfusion was free of bacteria in only one case, while 24 samples contained up to five different bacterial species including some strains not preexistent in the pharyngeal swabs. CONCLUSION: Blood collected from the site of operation is not suitable for retransfusion in maxillofacial surgery.

Adult↗
PubMed1997

[Antibiotic resistance of enterococci in Germany].

BACKGROUND: The resistance of enterococci against various antimicrobial substances including vancomycin has increased markedly. Since 1989 in the USA in particular high resistance rates against vancomycin have been observed but very few surveillance have been published in Europe. Therefore, we conducted a multicenter study in Germany to obtain information about the incidence and distribution of vancomycin and/or high-level aminoglycoside-resistant enterococci. METHODS: A total of 2046 enterococcal isolates were identified and susceptibility-testing was performed according to international guidelines. RESULTS: A total number of 90.5% of the enterococcal isolates were identified as Enterococcus faecalis and 7.8% was Enterococcus faecium. Resistance against ampicillin was detected in 56.6% of the Enterococcus faecium isolates, however, in only one Enterococcus faecalis isolate. High-level resistance against gentamycin or streptomycin was observed in 7.3% and 24.8% of the isolates, respectively. Twelve isolates showed resistance against vancomycin, however, cross resistance with teicoplanin was found in only two isolates. CONCLUSION: The rate of resistance of enterococci in Germany is still considerably lower than in the United States. Previous vancomycin therapy has been implemented as a risk factor for colonization or infection with vancomycin-resistant enterococci. Continued vigilance, decreased use of vancomycin and strict enforcement of infection control measures are appropriate measures to control the growing problem of resistant enterococci.

Ampicillin Resistance↗
PubMed1997

Increased adherence of Candida albicans to buccal epithelial cells from patients with AIDS.

The adherence of six clinical Candida albicans isolates to buccal epithelial cells obtained from AIDS patients, solid organ transplant recipients and healthy individuals was compared. It was shown that Candida albicans bound in significantly greater numbers to epithelial cells obtained from AIDS patients than to those from healthy individuals or transplant patients, and that the adherence capacity varied among the strains tested.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Phenyl valerate esterases other than neuropathy target esterase and the promotion of organophosphate polyneuropathy.

Certain esterase inhibitors (such as phenylmethanesulfonyl fluoride, PMSF) enhance the clinical and morphological signs of organophosphate-induced delayed polyneuropathy (OPIDP) in hens. This is called promotion of OPIDP. The target of promotion is unknown, but it is likely to be different from neuropathy target esterase (NTE), the target of OPIDP, NTE is a neural phenyl valerate (PV) esterase, operationally defined by selective inhibition with organophosphates. This study was aimed to ascertain whether the target for promotion is a PV esterase other than NTE. Brain and sciatic nerve PV esterases of hens were incubated with diisopropylphosphorofluoridate (DFP; 5 microM) or N,N-diisopropyl phosphorodiamidofluoridate (mipafox; 50 microM) to inhibit NTE and other esterases thought not to be relevant to promotion. Remaining activities, quantitatively similar after either inhibition, were titrated with PMSF (up to 500 microM) and analysis of time course of inhibition showed first-order kinetics. Mipafox (50 microM)-resistant PMSF (500 microM)-sensitive activity (about 80% of mipafox-resistant ones) was tested both in vitro and in vivo with several inhibitors. No correlation was found between inhibition of mipafox-resistant PMSF-sensitive activity and the capability of several inhibitors to promote OPIDP. We conclude that the target of promotion is unlikely to be a PV esterase resistant to mipafox (50 microM).

Animals↗
PubMed1997

Successful treatment of cerebral aspergillosis with a novel triazole (voriconazole) in a patient with acute leukaemia.

Invasive aspergillosis is an increasing problem in patients with acute leukaemia, bone marrow transplantation, immunosuppression after solid organ transplantation, or acquired immunodeficiency syndrome. Despite available antifungal treatment, the mortality approaches 100% in patients with dissemination of the infection into the central nervous system (CNS). Using a novel triazole, voriconazole, we successfully treated an Aspergillus brain abscess in a patient with acute leukaemia. Drug levels above the minimal fungicidal concentration for Aspergillus species were detected in cerebrospinal fluid (CSF) specimens, and the treatment achieved an objective response.

Acute Disease↗
PubMed1996

Modification of acetylcholinesterase during adaptation to chronic, subacute paraoxon application in rat.

These experiments examined the changes in acetylcholinesterase (AChE) during tolerance development in rats exposed to paraoxon, an irreversible inhibitor of AChE. Rats were injected sc for 20 days with 0.09, 0.12, or 0.19 mg/kg of paraoxon. Tolerance to the clinical signs of paraoxon toxicity developed rapidly. The hypothesis was tested that changes in the kinetics of reactivity of AChE with its substrate acetylcholine (ACh) and the inhibitor paraoxon contribute to the observed tolerance. The kinetic constants Vmax and Km were determined by Lineweaver-Burk transformations. The affinity (Kd), phosphorylation (kp) and the bimolecular rate (ki) constants were established from slopes and standard deviations of inhibition curves. Acetylcholinesterase properties of brain and diaphragm from controls and paraoxon-tolerant rats were compared. In controls, Km, determining the affinity of AChE for ACh, was 0.063 x 10(-3) M and 0.072 x 10(-3) M for diaphragm and brain, respectively. In paraoxon-tolerant rats, the affinity of AChE for ACh increased since the Km for diaphragm was reduced to 0.047 x 10(-3) M and the Km for brain to 0.057 x 10(-3) M. This decrease was seen with all paraoxon concentrations and was significantly different from controls after the fifth day of treatment. Small, significant increases of IC50 values for paraoxon were observed in diaphragm (from 27.30 to 45.14 nM) and in brain (from 13.67 to 15.38 nM). In brain, a 20-day treatment with paraoxon caused a fivefold decrease in the dissociation constant (Kd) from 1.56 to 0.268 microM and a threefold decrease in the phosphorylation constant (kp) from 4.72 to 1.52 min-1. The observed changes in diaphragm were smaller and not significant. The increase in affinity to ACh gives an advantage to tolerant rats, because the remaining reduced amount of AChE can hydrolyze ACh more efficiently, regardless of the change in sensitivity to the inhibitor. The observed changes may be the result of structural changes of AChE or the result of altered levels of preexisting isozymes of AChE.

Acetylcholinesterase↗
PubMed1996

In vitro activity of trovafloxacin in combination with ceftazidime, meropenem, and amikacin.

The in vitro activity of trovafloxacin alone and in combination with ceftazidime, meropenem, and amikacin was studied by determining the minimal inhibitory concentrations (MICs) for 111 gram-negative and 71 gram-positive bacteria. In addition, the synergy of these combinations against 46 strains of gram-negative and gram-positive organisms was studied by checkerboard titration and time-kill kinetics. Trovafloxacin exhibited excellent in vitro activity against all strains tested. Synergism was observed in 17% of the gram-negative strains and in 32% of the gram-positive strains. No antagonism was observed with any of the combinations tested.

Amikacin↗
PubMed1995

[Streptococcus B screening with GBS medium in obstetrics].

Pregnant women and newborn infants were screened for group B streptococcal (GBS) colonization by obtaining paired swabs from the cervix and urethra for the former group and from the ear, nose, umbilical cord, gastric juice and membranes for the latter. One swab was cultured on blood agar; the other was inoculated into serum-starch broth (GBS medium), which allows identification of GBS by production of a characteristic orange-colored pigment. From the 2105 paired swabs obtained, a total of 158 were GBS positive by either method; of these, 154 (97.5%) were recovered by the GBS medium and 89 (56.3%) by blood agar plate. No false positive color reactions were observed with GBS medium. 75% of the positive GBS media could be read within 24 h of incubation. The use of GBS medium proved to be an easy and reliable method for screening of maternal and neonatal GBS colonization.

Culture Media↗
PubMed1995

[In vitro activity of sparfloxacin against methicillin-resistant staphylococci].

The antimicrobial activity of sparfloxacin (CAS 110871-86-8) against 154 clinical isolates of methicillin-resistant staphylococci was investigated and compared with that of 6 other fluoroquinolones. The isolates consisted of 100 methicillin-resistant Staphylococcus aureus (MRSA), 29 Staphylococcus epidermidis (MRSE) and 25 other coagulase-negative staphylococci (CNS). Sparfloxacin was more active than ciprofloxacin and the other fluoroquinolones against all strains tested. The MIC90 of sparfloxacin against the 100 isolates of Staphylococcus aureus was 8 mg/l, while that of ciprofloxacin was > or = 64 mg/l. Moreover, ciprofloxacin-susceptible MRSA isolates were inhibited by sparfloxacin at a concentration of < or = 0.06 mg/l. The other quinolones had an MIC90 ranging from 0.5 mg/l to 4 mg/l against ciprofloxacin-susceptible MRSA. Similar results were obtained for the MRSE and CNS isolates tested. As many as 90% of the ciprofloxacin-susceptible microorganisms were inhibited at a concentration of < or = 0.06 mg/l or 0.125 mg/l of sparfloxacin. The MIC90 of sparfloxacin against ciprofloxacin-resistant CNS and MRSE were 4 mg/l and 8 mg/l, respectively. Sparfloxacin was clearly more active than any of the other quinolones against all species tested, although higher concentrations were needed to inhibit ciprofloxacin-resistant staphylococci.

Anti-Infective Agents↗
PubMed1994

Methicillin-resistant Staphylococcus aureus in Europe.

In order to obtain pan-European data on methicillin-resistant Staphylococcus aureus (MRSA), 43 laboratories from ten European countries each screened 200 consecutive Staphylococcus aureus isolates for methicillin resistance. Only one isolate per patient was permitted. All participants used a uniform oxacillin-supplemented screening plate. MRSA isolates were sent to Munich for reconfirmation and further susceptibility testing. Phage typing of the MRSA strains was performed in Denmark. Of the 7,333 Staphylococcus aureus strains screened, 936 (12.8%) were methicillin resistant. The proportion of MRSA in the various European countries ranged from < 1% in Scandinavia to > 30% in Spain, France and Italy. Rates of resistance to the non-glycopeptide antibiotics were lowest for rifampin and highest for ciprofloxacin. Sixty percent of the methicillin-resistant strains originated from patients in surgical and medical departments, with wounds being the most common isolation source. MRSA was found more frequently in intensive care patients. Only 13% of the strains were non-typable, and 76% of the isolates belonged to phage group III. For each area phage typing detected one or a few dominating (epidemic) types, but 46% of the strains did not belong to these types; the MRSA population is thus a mixture of epidemic and non-epidemic strains. MRSA seems to be a growing problem, especially in southern Europe, where incidence and rates of antibiotic resistance are alarmingly high.

Anti-Bacterial Agents↗
PubMed1994

[Comparative antibacterial activity of cefpodoxime against Haemophilus influenzae, Streptococcus pyogenes, Streptococcus pneumoniae and Moraxella catarrhalis].

The antimicrobial activity of cefpodoxime (Podomexef, CAS 80210-62-4) against 236 clinical isolates of H. influenzae, Moraxella catarrhalis, Streptococcus pyogenes and Streptococcus pneumoniae was investigated and compared with that of another 8 commonly used oral antibiotics. beta-Lactamase negative, beta-lactamase positive and multiresistant strains of H. influenzae were inhibited by cefpodoxime at a concentration of 0.13 mg/l. 10% of Moraxella catarrhalis isolates were moderately susceptible to cefpodoxime, with minimum inhibitory concentration (MIC) of cefpodoxime ranging between 0.13 and 2.0 mg/l. All isolates of Streptococcus pyogenes and Streptococcus pneumoniae were susceptible to < or = 0.25 mg/l cefpodoxime. Cefpodoxime was clearly more active than the older oral cephalosporins against all species tested. The activity was comparable to that of cefixime against all species except Streptococcus pneumoniae, against which cefpodoxime was more active than cefixime.

Bacteria↗
PubMed1993

Reactivation of phosphorodiamidated acetylcholinesterase and neuropathy target esterase by treatment of inhibited enzyme with potassium fluoride.

It has been thought that the phosphorus-enzyme bond in inhibited esterases inhibited by such agents as mipafox (N,N'-di-iso-propylphosphorodiamidate) was refractory to reactivating agents either because an 'aging' reaction occurs soon after inhibition or because the bond was intrinsically very strong. We have found that both acetylcholinesterase (AChE) and neuropathy target esterase (NTE) which had been inhibited with either mipafox or with a di-n-butylphosphorodiamidate could be reactivated by prolonged treatment with aqueous potassium fluoride (KF): the reaction proceeded with first-order kinetics. Furthermore there was no time-dependent loss of reactivatability (aging). Di-isopropylphosphoro-butyrylcholinesterase could be fully reactivated by this treatment but after 18 h to allow aging the monoisopropyl phosphoro-enzyme was totally refractory to KF. We conclude that it is likely that the mipafox-enzyme bond in inhibited NTE and AChE is relatively strong but that aging has not occurred. The local disturbance around the active site of NTE caused by attachment of the phosphorodiamidate molecule appears to be sufficient to initiate delayed neuropathy without necessity for an 'aging' reaction.

Acetylcholinesterase↗