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Mechanisms of 5-aminolevulinic acid uptake at the choroid plexus.

5-Aminolevulinic acid (5-ALA) is a precursor of porphyrins and heme that has been implicated in the neuropsychiatric symptoms associated with porphyrias. It is also being used clinically to delineate malignant gliomas. The blood-CSF barrier may be an important interface for 5-ALA transport between blood and brain as in vivo studies have indicated 5-ALA is taken up by the choroid plexuses whereas the normal blood-brain barrier appears to be relatively impermeable. This study examines the mechanisms of 5-[(3)H]ALA uptake into isolated rat lateral ventricle choroid plexuses. Results suggest that there are two uptake mechanisms. The first was a Na(+)-independent uptake system that was pH dependent (being stimulated at low pH). Uptake was inhibited by the dipeptide Gly-Gly and by cefadroxil, an alpha-amino-containing cephalosporin. These properties are the same as the proton-dependent peptide transporters PEPT1 and PEPT2, which have recently been shown to transport 5-ALA in frog oocyte expression experiments. Choroid plexus uptake was not inhibited by captopril, a PEPT1 inhibitor, suggesting PEPT2-mediated uptake. The presence of PEPT2 and absence of PEPT1 in the choroid plexus were confirmed by western blotting. The second potential mechanism was both Na(+) and HCO(3)(-) dependent and appears to be an organic anion transporter, although it is possible that removal of Na(+) and HCO(3)(-) may indirectly affect PEPT2 by affecting intracellular pH. The presence of PEPT2 and a putative Na(+)/HCO(3)(-)-dependent organic anion transporter is important not only for an understanding of 5-ALA movement between blood and brain but also because these transporters may affect the distribution of a number of drugs between blood and CSF.

Aminolevulinic Acid↗

Oral cephalosporins.

The arrival of new cephalosporins faces the clinician with an evergrowing confusion as to the drug of choice. The older agents (cephalexin, cephradine, cefadroxil and cefaclor) and the newer formulations cefatrizine and cefuroxime axetil are intensively used for treatment of mild and moderate infections. The oldest agents have a better pharmacokinetic profile but are less active against Gram-positives and Gram-negatives. Cefaclor, cefatrizine and cefuroxime axetil have improved in vitro activity against H. influenzae and/or against S. aureus and M. catarrhalis. However the mean free serum concentrations after proposed standard daily doses of cefaclor (3 x 250 mg/d), cefatrizine (2 x 500 mg/d) and cefuroxime-axetil (2 x 250 mg/d) are lower than those of the older cephalosporins. In comparison amoxicillin-clavulanate is equally efficacious, has a more reliable pharmacokinetic profile and is less expensive than cefaclor and cefuroxime axetil in a comparable dose (e.g. 3 x 500 mg/d).

Administration, Oral↗

In vitro development of resistance of Streptococcus pneumoniae to beta-lactam antibiotics.

In recent years, increasing numbers of Streptococcus pneumoniae strains displaying relative resistance to penicillin have been reported. Epidemiological studies have shown a correlation between aminopenicillin administration and resistance. We investigated the development of resistance in six strains (four sensitive and two intermediate-resistant to penicillin) by serial daily passages in subinhibitory concentrations of amoxicillin (AMX), amoxicillin + clavulanic acid (AMC), imipenem (IMP), cefixime (CFM), cefatrizine (CTZ), cefadroxil (CDX), and cefuroxime (CXM). MICs were determined by the macrodilution method in brain-heart broth for each daily passage. The number of daily passages needed to increase the MIC by a factor of 8 was achieved with AMX, AMC, and CFM for most of the strains after a mean of 24, 20, and 11 passages, respectively, and for one-third of the strains, with CDX, IMP, and CTZ after 11, 11, and 21 passages, respectively. Decreased susceptibility to breakpoints for intermediate-resistant S. pneumoniae populations was noted for all strains with CFM, AMX, and AMC after a mean of 10, 18, and 21 serial passages, respectively, and for four of five strains with IMP and CTZ after 12 and 13 passages. CTZ-, CDX-, and CXM-passaged variants had increased MIC values only for cephalosporins, while AMX-, AMC-, IMP-, and CFM-passaged variants exhibited increased MICs to all antibiotics tested. These in vitro data appear to be in agreement with epidemiological studies and warrant further exploration with respect to possible clinical implications.

Bacterial Typing Techniques↗

In-vitro studies with ciprofloxacin, a new 4-quinolone compound.

Ciprofloxacin is a new antibacterial agent of the 4-quinolone group. With an agar dilution technique we compared its activity on 365 clinical isolates with those of norfloxacin, nalidixic acid, ampicillin, mezlocillin, cefadroxil, cefuroxime, ceftazidime, ceftriazone , cefotaxime, latamoxef (moxalactam), and gentamicin. Ciprofloxacin was overall the most active agent tested against aerobic Gram-negative species, with the MIC90 values for all species being below 1 mg/l (excepting Providencia stuartii with 4 mg/l), and the large majority being below 0.12 mg/l. Many of the strains were selected on the basis of resistance to beta-lactam agents or gentamicin, and ciprofloxacin was also active against these. There was little difference in the activity of ciprofloxacin at inocula of 10(4) or 10(6) cfu. Strains with higher MIC's of the related agents norfloxacin and nalidixic acid were less susceptible to ciprofloxacin . Ciprofloxacin was less active against Gram-positive species (typical MIC90 values were 0.5 or 1 mg/l) and obligate anaerobes (4 mg/l for Bacteroides fragilis). The activity of ciprofloxacin in broth dilution tests was little affected by pH over the range 6.0-8.0, or by human serum or tissue fluid; its activity was reduced by the presence of urine. Binding to human serum protein was 20-28%. Ciprofloxacin was rapidly bacterial in broth at concentrations near to its MICs. By exposure to subinhibitory concentrations of ciprofloxacin it was possible to increase its MIC for bacteria in daily subcultures. The final MIC values after ten days were often about 16-fold greater than those observed initially.

Anti-Bacterial Agents↗

Interleukin-1 production by antibiotic-treated human monocytes.

The effects of penicillin, macrolides (spiramycin and erythromycin), cephalosporins (cefaclor and cefadroxil), tetracycline (doxycycline) and quinolones (pefloxacin, ciprofloxacin and ofloxacin) on extracellular and cell-associated interleukin 1 (IL-1) activity from human adherent mononuclear leucocyte cells were investigated in vitro. When cells were treated with an antibiotic concentration of 10 mg/l, no apparent effect could be detected for penicillin, erythromycin, cephalosporins or quinolones, while a slight increase of extracellular IL-1 activity associated with a decrease of intracellular IL-1 activity was observed with spiramycin and doxycycline. When high antibiotic concentration were used, extracellular IL-1 activity was increased by macrolides and tetracycline, while both cell-associated and class II human monocyte antigen expression were decreased. A toxic effect may have been exerted by these antimicrobial agents, since cell viability was altered when they were used at high concentrations. In contrast, extracellular IL-1 activity was found to be decreased by quinolones and cephalosporins. Intracellular IL-1 activity was also decreased by cephalosporins, while quinolones did not modify either cell-associated IL-1 activity or class II human monocyte antigen expression. The effect induced by quinolones and cephalosporins occurred without modification of cell viability. IL-1 activity was shown to be affected by antibiotics over the same range of concentrations which are known to inhibit mononuclear leucocyte proliferation. Our data may help in defining the mechanism by which the mitogen-induced mononuclear proliferative response is suppressed by antimicrobial agents since this appears to involve the inhibition of IL-1 production or of its release.

Anti-Bacterial Agents↗

Comparative in-vitro activity of a new oral carbacephem, LY163892.

The in-vitro activity of a new oral carbacephem, LY163892, was compared with cefaclor, cephalexin, cephradine, cefadroxil and selected penicillins against 529 bacterial isolates. LY163892 exhibited greater activity in vitro than all four cephalosporins against Haemophilus influenzae, beta-lactamase producing Branhamella catarrhalis, Escherichia coli, Klebsiella spp. and Proteus mirabilis. LY163892 had equivalent potency to cefaclor against non-beta-lactamase producing B. catarrhalis, streptococci and Staphylococcus aureus. Group D beta-haemolytic streptococci, Proteus vulgaris, and methicillin-resistant staphylococci were universally resistant to LY163892 and the four cephalosporins. Broth dilution experiments indicated that LY163892 was bactericidal against a range of Gram-positive and Gram-negative organisms and suggested that the antibiotic had a similar degree of stability to the beta-lactamases of H. influenzae, B. catarrhalis and Staph. aureus as did cefaclor. The susceptibility of 16 strains of H. influenzae to LY163892 and cefaclor were equivalent when estimated using three different commercially available agar media. Addition of carbon dioxide to the incubation atmosphere significantly reduced the potency of both drugs.

Bacteria↗

Resistance of bacterial pathogens to four aminoglycosides and six other antibacterials and prevalence of aminoglycoside modifying enzymes, in 20 UK centres.

A total of 5116 non-fastidious bacterial strains isolated from either blood or urine culture were collected from 20 geographically distributed centres within the UK. Upon receipt the strains were identified and the minimum inhibitory concentrations of ten antimicrobial agents in hospital usage were determined for each of the strains. All laboratories submitted a similar range of bacterial species and in species normally considered as sensitive the overall rates of resistance to the different antibiotics tested were: amikacin 2.4%, gentamicin 3.7%, netilmicin 2.6%, tobramycin 3.4%, ampicillin 41.7%, cefadroxil 11.6%, cefotaxime 1.4% [corrected], cefuroxime 4.3%, ciprofloxacin 0.6% and trimethoprim 13.0%. For those strains resistant to one or more aminoglycosides the mechanisms of resistance responsible were determined from the aminoglycoside-resistance patterns of the strains to 16 different aminoglycoside antibiotics. The predominant mechanisms of resistance found were APH(2") + AAC(6') production in staphylococci. AAC(2') production in Providencia spp., and AAC(3) production in the other Gram-negative genera.

Aminoglycosides↗

In-vitro activity of cefetamet (Ro 15-8074) compared with other oral agents.

The bacteriostatic and bactericidal activities of cefetamet (Ro 15-8074) were compared with those of cefadroxil, cefaclor, ampicillin, doxycycline, chloramphenicol and erythromycin against a total of 400 bacterial strains isolated from nosocomial respiratory tract and auditory canal infections. The broth macrodilution method was used to determine antimicrobial susceptibility. None of the compounds was effective against Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus strains. Cefetamet was very active against ampicillin-resistant Klebsiella pneumoniae. Proteus mirabilis and Escherichia coli strains with the minimal inhibitory concentrations for 90% of the strains tested ranging from 0.25 to 1 mg/l. Cefetamet at a concentration of 8 mg/l inhibited 90% of Enterobacter aerogenes and 60% of S. epidermidis strains. In biophotometric studies, subinhibitory concentrations of cefetamet greatly lengthened the lag-phase and flattened the log-phase, the extent varying with the concentrations and species tested. It did not cause detectable lysis in the stationary-phase of the cultures. Adding two to 32 times inhibitory concentrations of cefetamet to middle-log cultures, no or moderate lysis occurred., except with Esch. coli. This observation suggests that cefetamet is primarily bacteriostatic for some of the strains tested.

Anti-Bacterial Agents↗

The pharmacokinetics of the oral cephalosporins--a review.

The pharmacokinetics of the older and more recent oral cephalosporins are reviewed. With the exception of cefadroxil the older agents (cephalexin, cephradine and cefaclor) have serum elimination half-lives of less than or equal to 1 h and hence have to be administered three to four times daily. The urinary recovery of these agents is high (greater than 80% of oral dose) with the exception of cefaclor (54%). Cefaclor is also chemically unstable. The newer agents can be divided into those that are prodrugs (cefpodoxime proxetil and cefuroxime axetil) and compounds that are absorbed as such (cefixime, cefprozil and ceftibuten). They all have half-lives greater than 1.25 h and can be given once or twice daily. The penetration of these agents into an inflammatory exudate was studied and found to be cefixime 132%, ceftibuten 113%, cefpodoxime 104%, cefuroxime 92% and cefprozil 79% of the serum concentration. The penetration of cefpodoxime and cefixime into the respiratory tract was also studied; the mean percentage bronchial mucosal penetration was 52% for the former and 38% for cefixime. The urinary recovery of these newer agents (with the exception of ceftibuten) tends to be less than that of the earlier agents. There was a relationship between the serum elimination half-life of these agents and the degree of tissue penetration, those agents with longer half-lives penetrating to a greater extent.

Absorption↗

Surveillance of Streptococcus pneumoniae serotypes in Riyadh and their susceptibility to penicillin and other commonly prescribed antibiotics.

A total of 358 recent distinct isolates of Streptococcus pneumoniae were recovered from clinical specimens of patients in various hospitals in Riyadh, Saudi Arabia. The commonest serotypes were Groups C, F, B and A. Using specific monosera for typing it was found that serotype 14 was the commonest followed by serotypes 3, 7, 1, 2, 19 and 8 respectively. The minimal inhibitory concentrations (MIC) of penicillin determined by an agar dilution method, showed that 81% were susceptible (MIC less than 0.1 mg/L), 18% were relatively resistant (MIC = 0.1-1 mg/L) and 1% showed increased resistance (MIC greater than or equal to 1.0 mg/L). The use of a 1 microgram oxacillin disc distinguished between susceptible and relatively penicillin resistant pneumococci more reliably than did the use of a penicillin disc (1 or 10 micrograms). Resistance of S. pneumoniae to tetracycline, co-trimoxazole, chloramphenicol, and erythromycin were 70%, 43%, 12% and 4% respectively. All isolates were susceptible to oral cephalosporins (cefadroxil, cephalexin, cefaclor, and cefuroxime axetil) with an MIC range of less than or equal to 0.03-2 mg/L. The selection of antimicrobial therapy and the efficiency of vaccines depend on the knowledge of the local isolates of S. pneumoniae. Clinical isolates should be routinely screened to detect susceptibility to penicillin. The relatively high incidence of resistance to multiple antibiotics indicates the need to perform antibiotic susceptibility testing in order to avoid possible therapeutic failure.

Administration, Oral↗

Beta-lactam susceptibility of Haemophilus influenzae strains showing reduced susceptibility to cefuroxime.

Minimum inhibitory concentrations of 13 beta-lactam antibiotics (ampicillin, amoxycillin, amoxycillin/clavulanate, imipenem, cefazolin, cefadroxil, cefaclor, cefuroxime, cefotaxime, cefepime, cefpirome, cefpodoxime and cefixime), were determined for 76 strains of beta-lactamase negative Haemophilus influenzae, isolated over a five year period (1985-1990) that gave reduced zones to cefuroxime on disc testing when compared to the control strain H. influenzae NCTC 11931. MIC90 values for all antibiotics (except imipenem) were approximately ten times higher than the MIC90 values for a susceptible control group. Increased resistance was not associated with any particular biotype, although three biotype III strains were highly resistant to imipenem. More than 50% of strains with reduced susceptibility to beta-lactam antibiotics were isolated from patients with chronic respiratory disease. Published data on the sputum concentration of each antibiotic were compared to the MIC90 values obtained for the susceptible and resistant strains.

Anti-Bacterial Agents↗

Antibacterial activity of oral antibiotics against community-acquired respiratory pathogens from three European countries.

Antimicrobial resistance is universally recognized as a major problem. A European resistance survey was established to monitor the activity of widely used oral antibiotics against common respiratory tract pathogens. Studies were conducted in Italy, Spain and Austria to monitor resistance patterns among respiratory Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pyogenes, Staphylococcus aureus and Klebsiella pneumoniae to amoxicillin, co-amoxiclav, penicillin, cefaclor, cefadroxil, cefalexin, cefprozil, cefuroxime, cefixime, ceftibuten, cefpodoxime, clarithromycin and azithromycin (the antibiotics tested varying slightly from country to country). Minimum inhibitory concentrations were determined using the NCCLS-recommended broth microdilution method. Among the antibiotics tested, cefpodoxime, an oral cephalosporin, was remarkably active against the major respiratory pathogens in all three countries. Cefpodoxime was more potent than cefaclor, cefixime and ceftibuten against pneumococci, especially against strains with decreased sensitivity to penicillin, and more active than cefaclor and cefuroxime against Gram-negative respiratory pathogens. Pneumococci and staphylococci displayed a very high level of in vitro macrolide resistance. These data indicate that cefpodoxime represents an appropriate choice in the treatment of community-acquired respiratory tract infection in the three countries surveyed.

Administration, Oral↗

Non-hospital antimicrobial usage and resistance in community-acquired Escherichia coli urinary tract infection.

OBJECTIVES: To investigate the correlation between non-hospital antimicrobial consumption and resistance. METHODS: Information on the non-hospital sales of antimicrobials from 14 European countries in 1997 and 2000 was compared with the antimicrobial resistance profiles of Escherichia coli isolated from women with community-acquired urinary tract infection in the same countries in 1999/2000. RESULTS: There was no statistically significant correlation between the consumption of and resistance to co-amoxiclav, cefadroxil, fosfomycin, mecillinam, sulfamethoxazole, trimethoprim or trimethoprim-sulfamethoxazole. On the other hand, there were statistically significant correlations between consumption of broad-spectrum penicillins and quinolones in 1997 and 2000 and resistance to ciprofloxacin (P range 0.0005-0.0045) and nalidixic acid (P range 0.0013-0.0049). Total antimicrobial consumption in 1997 was significantly correlated to ciprofloxacin (P=0.0009) and nalidixic acid (P=0.0018) resistance, and there were significant relationships between quinolone consumption in both years and resistance to gentamicin (P range 0.0029-0.0043) and nitrofurantoin (P range 0.0003-0.0007). E. coli with multiple antimicrobial resistance were significantly more common in countries with high total antimicrobial consumption. CONCLUSIONS: Owing to the frequent presence of many possible confounding factors, antimicrobial resistance to one drug does not always correlate well to the consumption of the same drug or closely related drugs. This study showed that the degree of antimicrobial consumption was significantly correlated to the incidence of multidrug-resistant E. coli.

Adolescent↗

European Surveillance of Antimicrobial Consumption (ESAC): outpatient cephalosporin use in Europe.

BACKGROUND: Data on outpatient cephalosporin use in Europe were collected from 25 countries within the ESAC project, funded by DG SANCO of the European Commission, using the WHO ATC/DDD methodology. METHODS: For the period 1997-2003, data on outpatient use of systemic cephalosporins aggregated at the level of the active substance were collected and expressed in DDD (WHO, version 2004) per 1000 inhabitants per day (DID). Use was analysed in detail, using the new ATC codes J01DB, J01DC, J01DD and J01DE, introduced in the 2005 issue of the WHO ATC index and assigned to the four cephalosporin generations. RESULTS: Total outpatient cephalosporin use in 2003 varied by a factor of 270 between the country with the highest (6.18 DID in Greece) and lowest (0.02 DID in Denmark) use. First-, second- and third-generation cephalosporins were used most in 6, 16 and 3 countries, respectively. We observed fourth-generation use (mainly cefepime) in ambulatory care in 11 countries. From 1997 to 2003 cephalosporin use decreased in 13 countries, in France by more than 1 DID. A relative increase of second-generation (mainly cefuroxime) or third-generation use (mainly cefpodoxime or cefixime) by more than 10% in 12 countries coincided with an equally large decrease of first-generation use in eight countries (mainly cefadroxil, cefalexin or cefatrizine). In six countries, first-generation use increased, second-generation use decreased or both occurred. CONCLUSION: The new ATC codes allow a more detailed description of outpatient cephalosporin use. The variation in antibiotic use in Europe is most extreme for this class of antibiotics, suggesting that in many countries in Europe these antibiotics are prescribed inappropriately.

Anti-Bacterial Agents↗

In vitro activity of a new broad spectrum, beta-lactamase-stable oral cephalosporin, cefixime.

Cefixime is a new orally absorbed iminomethoxy, aminothiazolyl cephalosporin. It inhibits the majority, 90%, of Streptococcus pneumoniae, Streptococcus pyogenes, Branhamella catarrhalis, Haemophilus influenzae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and Neisseria gonorrhoeae at concentrations less than or equal to 0.25 micrograms/ml. It inhibits 90% of the other members of the Enterobacteriaceae at concentrations less than 1 microgram/ml, with the exception of some strains of Enterobacter spp., Citrobacter freundii and Morganella morganii, Cefixime does not inhibit enterococci, Listeria, Pseudomonas aeruginosa, Acinetobacter, Bacteroides spp. or staphylococci. In general, cefixime has in vitro activity superior to cephalexin, cephradine, cefadroxil and cefaclor against all bacteria with the exception of staphylococci. Cefixime is not destroyed by most of the common plasmid and chromosomal beta-lactamases and its activity is not reduced by serum, blood or urine. Cefixime overall has excellent in vitro activity against the commonly encountered respiratory and urinary tract pathogens.

Bacteria↗

Overview of the safety profile of clarithromycin suspension in pediatric patients.

Results of preclinical studies conducted to characterize the safety of clarithromycin oral suspension in juvenile mice, rats and dogs as compared with that in adult animals indicate that there is no enhanced risk in younger animals. Adverse events in these preclinical studies mainly involved decreased body and increased liver and kidney weights. The safety profile of clarithromycin suspension also has been evaluated in Phase II (pharmacokinetic) and III (clinical) United States and international clinical trials conducted in pediatric patients. The most frequently reported adverse events occurring among the 1676 patients studied who received clarithromycin suspension in Phase III trials included diarrhea (7%), vomiting (6%), abdominal pain (2%), headache (2%) and nausea (1%). Adverse events were not serious and were usually rapidly reversible. Adverse event rates did not vary with sex or race. Overall adverse event rates were generally similar to those of comparator beta-lactam suspensions (i.e. amoxicillin, amoxicillin/clavulanate, penicillin VK, cefaclor, cefadroxil). With regard to specific gastrointestinal events, however, clarithromycin was better tolerated than amoxicillin/clavulanate whereas penicillin VK showed a lower incidence of gastrointestinal events. Overall clarithromycin oral suspension appears to be safe and well-tolerated, making it suitable for use in the pediatric population.

Animals↗

Minimum inhibitory concentrations for 25 selected antimicrobial agents against Dichelobacter nodosus and Fusobacterium strains isolated from footrot in sheep of Portugal and Spain.

The agar dilution method was used to determine the inhibitory activity of 25 antimicrobial agents against 69 strains of Dichelobacter nodosus and 108 strains of the genus Fusobacterium, all of which were isolated from 90 clinical cases of ovine footrot between October 1998 and November 2000. In the case of the micro-organisms belonging to the genus Fusobacterium, the six beta-lactams studied (benzyl penicillin, ampicillin, cloxacillin, cefadroxil, cefuroxime and cephalexine) proved to be, in general, the most effective antimicrobial agents. Chloramphenicol, clindamycin and doxycycline were also quite active against Fusobacterium spp. With regard to the 69 strains of D. nodosus tested, the levels of resistance remain low.

Animals↗

Medication use for pediatric upper respiratory tract infections.

The present study monitored medication prescribing patterns to patients treated for upper respiratory tract infections (URTIs) in the pediatric outpatient department (OPD) at Central Referral Hospital (CRH), Gangtok, Sikkim. A total of 562 URTI prescriptions of children, aged 0-12 years attending pediatric OPD at CRH, Sikkim were collected by a random once-weekly survey between May 2002 and April 2003. Males numbered 284 (50.5%), and females 278 (49.5%). Most of the patients in our study were aged 2-5 years (preschool children) (44.8%). The average number of medications prescribed per encounter was 2.37; 59.2% (789) of medicines were fixed-dose combination (FDC) products and two-thirds of FDCs were respiratory medicines (521). The most commonly prescribed medicines were respiratory medicines (47% of the total medicines prescribed). Others were antimicrobials (30.7%) and analgesic-antipyretics (18.8%). Among respiratory medicines, cough and cold preparations (prescribed in 13 different FDC products in 25 brand names) were prescribed most frequently (62%) followed by nasal preparations (21%) and beta(2) adrenergic agonist inhalers (9.2%). Ninety-eight percent of nasal preparations were isotonic saline drops (129). Antihistaminics (41.8%), non-opioid antitussives (13.5%), alpha agonist oral decongestants (42.3%), expectorants (32.2%), mucolytics (18.7%), paracetamol (14.7%), and beta(2) agonists (17.2%) were common ingredients of respiratory medicine combinations. Antihistamines (2.5%) and beta(2) agonists (9.2%) were used alone. The most commonly prescribed antimicrobial was amoxicillin with clavulanate (28.4%) followed by cefadroxil (20%), cotrimoxazole (9.5%) and amoxicillin alone (9.3%). Average number of antimicrobials prescribed was 0.7 (409/562). The most commonly prescribed analgesic-antipyretic was paracetamol (81.3%) followed by combination of ibuprofen and paracetamol (12.4%) and nimesulide (5.6%). Medication selection was rational in few cases. Various anomalies were observed in various aspects of drug use in children for URTI's. The main aim of the initiative is the need for more rational medicine use in URTIs in children for improvement of clinical effectiveness, cost effectiveness and reduction of potential useless risk of side effects.

Analgesics↗