Cefuroxime Axetil Research Articles

Antibiotic use profile at paediatric clinics in two transitional countries

In this study, we evaluated antibiotic utilisation pattern at two paediatric clinics in different European (transitional) countries: Croatia (Rijeka) and Russia (Smolensk). Antibiotic utilisation during the year 2000 was observed using the ATC/defined daily doses (DDD) methodology (ATC code-J01). Drug-usage data was expressed in numbers of DDD/100 bed-days and the DU90% profile. In Rijeka, 35 different systemic antibiotics were used and in Smolensk 22. The overall consumption of antibiotic drugs in Rijeka was more than three times higher than in Smolensk (28.96 vs 8.3 DDD/100 bed-days). The top five antibiotic drugs used in Smolensk were amoxicillin, mydecamicin, ampicilin, doxycylin, gentamicin; and in Rijeka cefuroxime axetil, ceftriaxone, azytromycin, ceftibuten and amoxicillin. Differences in antibiotic prescribing patterns are greater than expected. The pattern of antibiotic utilisation in both countries implies that regional control measures and guidelines for antibiotic use in children should be urgently established.

Evaluation of stability of cefuroxime axetil in solid state

The effect of temperature and relative atmospheric humidity on the stability of the crystalline form of cefuroxime axetil (CFA) in solid state was investigated. CFA is a mixture of diastereomers A and B. Changes in the concentration of the two diastereomers (A and B) of CFA were recorded by means of HPLC with UV detection. The degradation of diastereomers of CFA occurring at 0% relative humidity (RH) of the ambient air is a reversible first order reaction, while that occurring in humid air (RH>50%) is an autocatalytic first order reaction relative to substrate concentration. Although it has been found, that diastereomer B is the more stable isomer, humidity has a stronger effect on this very diastereomer.

Antibiotic prescribing for adults and children in Israeli emergency rooms

The emergency room (ER) is an important focal point for the initiation of antimicrobial therapy but there are few data on antimicrobial prescribing in the ER. The objective of the study was to describe antimicrobial prescribing in Israeli ERs and to compare patterns of prescribing between four different ERs in Northern Israel. The medical records of all patients who attended the ERs during February 2001 were examined. Those patients who were discharged home with a prescription for an antibiotic formed the sample. Paediatric data were only available for two of the four ERs. A total of 970 adults and 470 children attended the four ERs during 1 month and were discharged home with an antibiotic prescription representing 14.6 and 19.9%, respectively, of the total number of patients who visited the ERs. The most common diagnosis leading to an antibiotic prescription was respiratory tract infections (64 in adults and 90% in children). In adults, cefuroxime–axetil and amoxycillin–clavulanate (both second-line antibiotics) were the most frequently prescribed antibiotics, together accounting for 50% of all antibiotic prescriptions, while in children amoxycillin–clavulanate was favoured (58.9%). ‘Viral infections’ accounted for 22.5% of all prescriptions in adults, but only 2.3% in children. Otitis media accounted for almost half of all prescriptions in children. For some diagnoses, such as pneumonia in adults and tonsillitis in children, there was uniformity of prescribing among the different ERs, while for other diagnoses, there were large discrepancies. The ER represents an important source of inappropriate antibiotic prescribing, and measures to curb inappropriate prescribing are urgently needed.

Antibiotic resistance of E. coli in sewage and sludge

The aim of the study is the evaluation of resistance patterns of E. coli in wastewater treatment plants without an evaluation of basic antibiotic resistance mechanisms. Investigations have been done in sewage, sludge and receiving waters from three different sewage treatment plants in southern Austria. A total of 767 E. coli isolates were tested regarding their resistance to 24 different antibiotics. The highest resistance rates were found in E. coli strains of a sewage treatment plant which treats not only municipal sewage but also sewage from a hospital. Among the antimicrobial agents tested, the highest resistance rates in the penicillin group were found for Ampicillin (AM) (up to 18%) and Piperacillin (PIP) (up to 12%); in the cephalosporin group for Cefalothin (CF) (up to 35%) and Cefuroxime-Axetil (CXMAX) (up to 11%); in the group of quinolones for Nalidixic acid (NA) (up to 15%); and for Trimethoprime/Sulfamethoxazole (SXT) (up to 13%) and for Tetracycline (TE) (57%). Median values for E. coli in the inflow (crude sewage) of the plants were between 2.0×10 4 and 6.1×10 4 CFU/ml (Coli ID-agar, BioMerieux 42017) but showed a 200-fold reduction in all three plants in the effluent. Nevertheless, more than 10 2 CFU E. coli/ml reached the receiving water and thus sewage treatment processes contribute to the dissemination of resistant bacteria in the environment.

How can we predict bacterial eradication?

Antimicrobial efficacy is measured in vitro by determination of minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of antimicrobials, but these values do not account for fluctuations of drug concentrations within the body or the time course of the drug's in vivo antibacterial activity. However, in vivo bacteriologic efficacy can be predicted by pharmacokinetic/pharmacodynamic (PK/PD) parameters, such as the time for which teh serum drug concentration is above the MIC ( T>MIC), the ratio of peak serum concentration to the MIC, and the ratio of the area under the 24-h serum concentration-time curve to the MIC (AUC/MIC). Different patterns of antibacterial activity correlate with different PK/PD parameters. For example, a T>MIC of 40–50% of the dosing interval is a good predictor of bacteriologic efficacy for penicillins, cephalosphorins, and most macrolides, and an AUC/MIC ratio of at least 25 is required for efficacy with fluoroquinolones and azalides. The PK/PD breakpoint for susceptibility of an organism to a specific dosing regimen of an agent can be determined as the highest MIC met by the relevant PK/PD parameter for bacteriologic efficacy for that agent. These parameters have been validated extensively in animal models, as well as in many human studies where bacteriologic outcome has been determined. The PK/PD breakpoint of an agent is determined primarily by the dosing regimen, and generally applies to all pathogens causing disease at sites where extracellular tissue levels are similar to non-protein-bound serum levels. On this basis, many parenteral β-lactams are active against almost all strains of Streptococcus pneumoniae, including ‘penicillin-non-susceptible’ strains, in all body sites except for the central nervous system. Application of PK/PD breakpoints to standard dosing regimens of oral β-lactams predicts that agents such as cefaclor and defixime will have efficacy only against penicillin-susceptible strains of S. pneumoniae, while cefuroxime axetil, cefpodoxine and cefdinir will be effective against all penicillin-susceptible as well as many penicillin-intermediate strains. However, the most active oral β-lactams, amoxicillin and amoxicillin-clavulanate, have predicted efficacy against all penicillin-susceptible and -intermediate pneumococci, as well as against most penicillin-resistant strains, at amoxicillin doses of 45–90 mg/kg per day in children and 1.75 – 4.0 g/day in adults. These predictions are supported by evidence from animal studies of bacteriologic efficacy. The use of PK/PD parameters to predict bacterial eradication therefore allows an evidence-based approach to the selection of appropriate antimicrobial therapy.

Oral gemifloxacin once daily for 5 days compared with sequential therapy with i.v. ceftriaxone/oral cefuroxime (maximum of 10 days) in the treatment of hospitalized patients with acute exacerbations of chronic bronchitis

In a randomized, open-label, controlled, multicentre study, the clinical and bacteriological efficacy, safety and tolerability of oral gemifloxacin (320 mg once daily, 5 days) was compared with sequential intravenous (i.v.) ceftriaxone (1 g once daily, maximum 3 days) followed by oral cefuroxime axetil (500 mg twice daily, maximum 7 days) in adult hospitalized patients with acute exacerbations of chronic bronchitis (AECB) ( n = 274). The clinical success rates at follow-up (21–28 days post-therapy) in the clinical per-protocol population (the primary endpoint) were 86.8% (105/121) for gemifloxacin vs. 81.3% (91/112) for ceftriaxone/cefuroxime (treatment difference = 5.5, 95% CI −3.9, 14.9). The corresponding clinical results in the clinical intention-to-treat (ITT) population were 82.6% (114/138) vs. 72.1% (98/136), respectively (treatment difference = 10.5, 95% CI 0.7, 20.4). Thus, gemifloxacin had significantly higher clinical success rates than ceftriaxone/cefuroxime. The median time to discharge was 9 days in the gemifloxacin group vs. 11 days in the ceftriaxone/cefuroxime group ( P = 0.04, Wilcoxon test). At follow-up, 120/138 (87.0%) gemifloxacin-treated patients had been discharged from hospital, compared with 111/136 (81.6%) ceftriaxone/cefuroxime-treated patients in the clinical ITT population. Both treatments were generally well tolerated and there was no significant difference between the treatment groups in the incidence or type of adverse events reported. A 5-day course of oral gemifloxacin was shown by this study to be at least equivalent to sequential i.v. ceftriaxone/cefuroxime axetil (for up to 10 days) in patients with AECB who require hospital treatment.

Diagnosis, treatment, and prevention of Lyme disease in children.

The approaches to diagnosing and treating Lyme disease (LD) have been improved and refined as a result of basic and clinical research, and considerable practical experience. In addition, there have been recent studies that have allowed improvements in the ability to prevent infection with Borrelia burgdorferi. This paper will review the relevant literature and address recent developments in the diagnosis, treatment, and prevention of LD. Issues specifically related to the management of children will be identified. Controversies regarding treatment approaches will be examined in some detail. Understanding the clinical manifestations, or stage, of LD is crucial when approaching both diagnosis and treatment. Early localized disease is best diagnosed by recognizing the characteristic skin lesion, erythema migrans. Early disease will frequently, but not always, be accompanied by a detectable antibody response, particularly IgM antibody to the spirochete. Late disease, chiefly arthritis, is generally associated with high levels of IgG antibody. Western blot technology allows confirmation of enzyme immunoassay results and is especially useful when the latter is in the low or equivocal range. Early localized disease responds well to oral antibacterial therapy. Early disseminated disease, often associated with neurologic findings, may require parenteral therapy. The arthritis associated with LD frequently responds to oral antibacterials, but some refractory cases may require intravenous therapy, and occasionally surgery. Doxycycline is the oral antibacterial of choice, while amoxicillin and cefuroxime axetil are alternatives that may be preferred in young children. Owing to its long half-life and once daily dose administration, intravenous ceftriaxone has become the accepted standard for parenteral therapy. Tick avoidance has long been the mainstay for preventing LD. Antibacterial prophylaxis, using doxycycline, for tick bites has been shown to be an effective approach to prevention, but its relevance to pediatrics is uncertain. Vaccines designed to prevent infection have also been developed.

Diagnosis, Treatment, and Prevention of Lyme Disease in Children

The approaches to diagnosing and treating Lyme disease (LD) have been improved and refined as a result of basic and clinical research, and considerable practical experience. In addition, there have been recent studies that have allowed improvements in the ability to prevent infection with Borrelia burgdorferi. This paper will review the relevant literature and address recent developments in the diagnosis, treatment, and prevention of LD. Issues specifically related to the management of children will be identified. Controversies regarding treatment approaches will be examined in some detail.Understanding the clinical manifestations, or stage, of LD is crucial when approaching both diagnosis and treatment. Early localized disease is best diagnosed by recognizing the characteristic skin lesion, erythema migrans. Early disease will frequently, but not always, be accompanied by a detectable antibody response, particularly IgM antibody to the spirochete. Late disease, chiefly arthritis, is generally associated with high levels of IgG antibody. Western blot technology allows confirmation of enzyme immunoassay results and is especially useful when the latter is in the low or equivocal range.Early localized disease responds well to oral antibacterial therapy. Early disseminated disease, often associated with neurologic findings, may require parenteral therapy. The arthritis associated with LD frequently responds to oral antibacterials, but some refractory cases may require intravenous therapy, and occasionally surgery. Doxycycline is the oral antibacterial of choice, while amoxicillin and cefuroxime axetil are alternatives that may be preferred in young children. Owing to its long half-life and once daily dose administration, intravenous ceftriaxone has become the accepted standard for parenteral therapy.Tick avoidance has long been the mainstay for preventing LD. Antibacterial prophylaxis, using doxycycline, for tick bites has been shown to be an effective approach to prevention, but its relevance to pediatrics is uncertain. Vaccines designed to prevent infection have also been developed.

Levofloxacin

Levofloxacin (Levaquin) is a fluoroquinolone antibacterial agent with a broad spectrum of activity against Gram-positive and Gram-negative bacteria and atypical respiratory pathogens. It is active against both penicillin-susceptible and penicillin-resistant Streptococcus pneumoniae. The prevalence of S. pneumoniae resistance to levofloxacin is <1% overall in the US.A number of randomised comparative trials in the US have demonstrated the efficacy of levofloxacin in the treatment of infections of the respiratory tract, genitourinary tract, skin and skin structures. Sequential intravenous to oral levofloxacin 750mg once daily for 7-14 days was as effective in the treatment of nosocomial pneumonia as intravenous imipenem/cilastatin 500-1000mg every 6-8 hours followed by oral ciprofloxacin 750mg twice daily in one study. In patients with mild to severe community-acquired pneumonia (CAP), intravenous and/or oral levofloxacin 500mg once daily for 7-14 days achieved clinical and bacteriological response rates similar to those with comparator agents, including amoxicillin/clavulanic acid, clarithromycin, azithromycin, ceftriaxone and/or cefuroxime axetil and gatifloxacin. A recent study indicates that intravenous or oral levofloxacin 750mg once daily for 5 days is as effective as 500mg once daily for 10 days, in the treatment of mild to severe CAP. Exacerbations of chronic bronchitis and acute maxillary sinusitis respond well to treatment with oral levofloxacin 500mg once daily for 7 and 10-14 days, respectively. Oral levofloxacin was as effective as ofloxacin in uncomplicated urinary tract infections and ciprofloxacin or lomefloxacin in complicated urinary tract infections. In men with chronic bacterial prostatitis treated for 28 days, oral levofloxacin 500mg once daily achieved similar clinical and bacteriological response rates to oral ciprofloxacin 500mg twice daily. Uncomplicated skin infections responded well to oral levofloxacin 500mg once daily for 7-10 days, while in complicated skin infections intravenous and/or oral levofloxacin 750mg for 7-14 days was at least as effective as intravenous ticarcillin/clavulanic acid (+/- switch to oral amoxicillin/clavulanic acid) administered for the same duration. Levofloxacin is generally well tolerated, with the most frequently reported adverse events being nausea and diarrhoea; in comparison with some other quinolones it has a low photosensitising potential and clinically significant cardiac and hepatic adverse events are rare. Levofloxacin is a broad-spectrum antibacterial agent with activity against a range of Gram-positive and Gram-negative bacteria and atypical organisms. It provides clinical and bacteriological efficacy in a range of infections, including those caused by both penicillin-susceptible and -resistant strains of S. pneumoniae. Levofloxacin is well tolerated, and is associated with few of the phototoxic, cardiac or hepatic adverse events seen with some other quinolones. It also has a pharmacokinetic profile that is compatible with once-daily administration and allows for sequential intravenous to oral therapy. The recent approvals in the US for use in the treatment of nosocomial pneumonia and chronic bacterial prostatitis, and the introduction of a short-course, high-dose regimen for use in CAP, further extend the role of levofloxacin in treating bacterial infections.

Speed of Recovery from Acute Exacerbations of Chronic Obstructive Pulmonary Disease after Treatment with Antimicrobials

We performed a multicentre study under a 2-year observational protocol that included data on time to recovery from acute exacerbations of chronic obstructive pulmonary disease (AE-COPD) in patients receiving moxifloxacin and comparator antimicrobials. Outpatients with moderate or severe COPD were recruited from respiratory clinics throughout Spain. Moxifloxacin was available in year 2, and was to be prescribed to 50% of patients in that period in a non-randomised allocation. Time to recovery was compared in successfully treated AE-COPD; cross-sectionally for all AE-COPD over 2 years, first AE-COPD and all AE-COPD in year 2, and longitudinally in patients receiving comparator antimicrobials for AE-COPD in year 1 and moxifloxacin in year 2. 614 AE-COPD were treated in 441 patients over 2 years (mean age 66.7 +/- 8.3 years, 98% males, mean forced expiratory volume in 1 second [FEV(1)] 35.9 +/- 8.8%). Mean time to recovery overall was 4.6 days (SD 3.3) with moxifloxacin 400 mg/day for 5 days, and 5.8 days (SD 4.6) with comparators (p < 0.01), which were most frequently amoxicillin/clavulanic acid 500/125mg/8h, clarithromycin 500mg/12h and cefuroxime axetil 500mg/12h for 7-10 days. Longitudinal analysis showed that 27 patients treated with moxifloxacin in the second year of the study recovered in a mean of 3.7 days (SD 3.1), and the same patients treated with comparator antimicrobials in year one recovered in a mean of 6.8 days (SD 4.6) [p = 0.02]. In contrast, in 66 patients treated with comparator antimicrobials in both years, mean time to recovery was 7.4 days (SD 7.3) in year one and 5.5 days (SD 3.5) in year two (p = 0.24). All subgroup analyses showed a statistically significant reduction of 18-25% in time to recovery with moxifloxacin compared with other antibiotics. Moxifloxacin significantly reduced time to recovery from AE-COPD in patients with moderate to severe disease by approximately 20% (>1 day) compared with other antimicrobials. Faster recovery should result in earlier return to work or normal activities, and to social and economic savings.

GCF concentration and minimal inhibitory concentration of cefuroxime axetil against periodontopathogens

GCF concentration and minimal inhibitory concentration of cefuroxime axetil against periodontopathogens

Clinical microbiological case: severe relapsing septal panniculitis in a healthy man from the south-eastern USA

A 34-year-old, healthy caucasian man presented with relapsing, painful nodular lesions involving both the upper and lower extremities. His symptoms commenced eight weeks after burying two domestic cats that had died suddenly. He complained of profound fatigue, generalized myalgia, and joint pain, although he denied having cough, fever, and night sweats. An 8-cm arciform lesion on the anterior–medial aspect of the right upper arm had bright erythematous borders and a violaceous center. He was afebrile with small, non-tender, generalized lymphadenopathy. Ophthalmologic examination was normal. His white blood cell count was 11 700 cells/μ.L and his platelet count was 388 000/μ.L. Serum aminotransferase and ACE levels, and erythrocyte sedimentation rate were normal. His symptoms worsened after two weeks of oral methylprednisolone and cefuroxime axetil (500 mg twice daily) treatment. Histologic examination of the right arm lesion showed severe panniculitis with prominent necrosis of subcutaneous fat (Figure 1). Stains for acid-fast bacilli (Ziehl–Neelsen), fungi (GMS), and bacteria (Brown–Hopps, Brown–Brenn), and Warthin–Starry stain, were negative. Blood and tissue cultures were sterile. CT scan showed a normal liver, spleen, and intrathoracic and abdominal lymph nodes. A whole-body gallium scan was normal. 1What is your clinical diagnosis?2What are the common diseases associated with this infection?3What cutaneous manifestations are frequently seen in this setting?4What is the optimal treatment?

Open-label, randomized comparison of the efficacy and tolerability of clarithromycin, levofloxacin, and cefuroxime axetil in the treatment of adults with acute bacterial exacerbations of chronic bronchitis

Background: In the absence of a confirmed pathogen, empiric antimicrobial treatment of patients with acute exacerbations of chronic bronchitis and acute bacterial exacerbations of chronic bronchitis (ABECB) is accepted as standard practice and recommended in treatment guidelines. Objective: This study compared the efficacy and tolerability of a 10-day course of 3 antimicrobial regimens commonly used to treat adults with ABECB. Methods: This prospective, open-label, randomized study assessed clarithromycin 500 mg twice daily, levofloxacin 500 mg once daily, and cefuroxime axetil 250 mg twice daily, each administered for 10 days with food, in patients with ABECB. Efficacy was determined on the basis of the clinical response to treatment and need for hospitalization and/or further antimicrobial therapy. Results: A total of 283 patients (150 men, 133 women) with a mean age of 55 years (range, 29 to 86 years) were randomized to receive clarithromycin (n = 97), levofloxacin (n = 94), or cefuroxime axetil (n = 92). Of 262 clinically assessable patients, clinical cure or improvement occurred in 87.9% (80/91) of those treated with clarithromycin, 87.4% (76/87) of those treated with levofloxacin, and 79.8% (67/84) of those treated with cefuroxime axetil. Eight (8.8%) clarithromycin-treated patients, 6 (6.9%) levofloxacin-treated patients, and 12 (14.3%) cefuroxime axetil—treated patients required a change in antimicrobial therapy to achieve clinical cure/improvement; between-group differences were not significant. No patients treated with clarithromycin required hospitalization for further antimicrobial treatment, compared with 3.4% (3/87) of levofloxacin-treated and 3.6% (3/84) of cefuroxime axetil—treated patients ( P = NS). A total of 6.2% (6/97) of clarithromycin-treated patients were prematurely discontinued from treatment due to adverse events, compared with 7.4% (7/94) and 8.7% (8/92) of levofloxacin- and cefuroxime axetil—treated patients, respectively. Conclusion: A high rate of clinical efficacy and tolerability was observed in this population of patients with ABECB treated with clarithromycin 500 mg twice daily, levofloxacin 500 mg once daily, or cefuroxime axetil 250 mg twice daily for 10 days.

Haemophilus influenzae in respiratory tract infections in community-based clinical practice: therapy with gatifloxacin

In this community-based safety surveillance study, the advanced-generation fluoroquinolone gatifloxacin was administered empirically to 15,625 adults with community-acquired respiratory tract infections (RTIs), including 1562 clinically evaluable patients with community-acquired pneumonia (CAP) and 2391 with acute exacerbations of chronic bronchitis (AECB). Haemophilus influenzae was the most common pathogen isolated in AECB (40.1%) and the second most common in CAP (36.8%). In vitro susceptibility to gatifloxacin and other fluoroquinolones, amoxicillin/clavulanate, ceftriaxone, cefuroxime axetil, tetracycline, and azithromycin ranged from 95.8% to 100%. In comparison, a significant percentage of the isolates were not susceptible to clarithromycin (∼41%), ampicillin (22% to 28%), and trimethoprim/sulfamethoxazole (14% to 18%). The susceptibility pattern was generally independent of exposure to another antimicrobial in the previous 30 days. CAP and AECB patients infected with H. influenzae had signs and symptoms similar to those infected with Streptococcus pneumoniae. Among clinically evaluable patients with H. influenzae, gatifloxacin cured 159 of 166 (95.8%) with AECB and 112 of 118 (94.9%) with CAP. The cure rate was independent of the β-lactamase status or serotype of the H. influenzae strain. H. influenzae is not a more benign pathogen in community-acquired RTIs but causes signs and symptoms that are indistinguishable from those caused by other pathogens, notably S. pneumoniae.

Amoxicillin, cefuroxime axetil efficacious in early Lyme disease

Amoxicillin, cefuroxime axetil efficacious in early Lyme disease

비결정성 세푸록심 악세틸 고체분산체의 제조 및 평가

Cefuroxime axetil is a cephalosporin antibiotic having a high activity against a wide spectrum of Grampositive and Gram-negative microorganisms. It is a cephalosporin antibiotic which exist as 2 diastereoisomers: diastereoisomer A and B. It shows polymorphism of three forms: a crystalline form having a melting point of about , a substantially amorphous form having a high melting point of about and a substantially amorphous form having a low melting point of about . The crystalline form of cefuroxime axetil is slightly soluble in water because diastereoisomer A has lower solubility than B in water. Substantially amorphous form of which there are no difference in solubility between diastereoisomer A and B has better solubility than crystalline form, but it forms a thicker gel than crystalline form upon contact with an aqueous medium. Based on this reason, cefuroxime axetil is not readily absorbable in the gastrointestinal tract, rendering its bioavailability on oral administration very low. The object of this study was to develop an improved non-crystalline cefuroxime axetil composition having a high physicochemical stability and bioavailability. A non-crystalline cefuroxime axetil solid dispersant showing no peak on a Differential Scanning Calorimetry (DSC) scan is prepared by dissolving cefuroxime axetil and a surfactant in an organic solvent; suspending a water-insoluble inorganic carrier in the resulting solution; and spray drying the resulting suspension to remove the organic solvent, said solid dispersant having an enhanced dissolution and stability of cefuroxime axetil and being useful for the preparation of a pharmaceutical composition for oral administration. Tablet was formulated with this cefuroxime axetil solid dispersant, disintegrants and other ingredients. It disintegrated and dissolved easily and dynamically in dissolution medium, so showed a good dissolution profile.

Diagnosis and management of acute otitis media in the urgent care setting

The prevalence of otitis media is increasing, which affects health care resource utilization across all segments, including the urgent care setting. One of the greatest challenges in the management of acute otitis media (AOM) is the effective treatment of cases caused by pathogens that are resistant to commonly used antibiotics. Whereas the production of β-lactamases among strains of Haemophilus influenzae and Moraxella catarrhalis is an important consideration for antimicrobial therapy, the high prevalence of resistance to penicillin and other classes of antibiotics among strains of Streptococcus pneumoniae represents a greater clinical concern. The Centers for Disease Control and Prevention (CDC) recently convened the Drug Resistant S. pneumoniae Therapeutic Working Group to develop evidence-based recommendations for the treatment of AOM in an era of prevalent resistance. The recommendations from this group included amoxicillin as the preferred first-line drug because of the demonstrated activity against penicillin-intermediate and -resistant strains of S. pneumoniae, using higher dosages of up to 90 mg/kg per day in certain settings. For patients in whom initial treatment is unsuccessful after 3 days, the recommended agents included high-dose amoxicillin-clavulanate (for activity against β-lactamase-producing pathogens), clindamycin, cefuroxime axetil, or 1 to 3 doses of intramuscular ceftriaxone. The principles set forth in these guidelines can assist the therapeutic decisionmaking process for practitioners in the urgent care setting. [McCracken GH Jr. Diagnosis and management of acute otitis media in the urgent care setting. Ann Emerg Med. April 2002;39:413-421.]

Intestinal transport of cefuroxime axetil in rats: absorption and hydrolysis processes

Studies were performed using three cefuroxime axetil solutions (11.8, 118 and 200 μM) in three selected intestinal segments and one cefuroxime axetil solution (118 μM) in colon of anaesthetized rats. First-order absorption rate pseudoconstants, k ap and effective permeability coefficients, P eff, were calculated in each set. Absorption of cefuroxime axetil can apparently be described as a carrier-mediated transport, which obeys Michaelis–Menten and first order kinetics in the proximal segment of the small intestine and a passive diffusion mechanism in the mean and distal segments. The absorption kinetic parameters for cefuroxime axetil were obtained: V m=0.613 (0.440) μM min −1; K m=31.49(28.31) μM and k a=0.011(0.003) min −1. Parameters characterizing degradation of the prodrug were obtained in each intestinal segment: proximal segment k dp=0.0049(0.0003) min −1, mean segment, k dm=0.0131(0.0007) min −1 and distal segment k dd=0.019(0.0009) min −1. Therefore, in situ intestinal absorption of cefuroxime axetil in the proximal segment of the rat in the presence of variable concentrations of cefadroxil has been investigated in order to examine the inhibitory effect of cefadroxil on cefuroxime axetil transport. The data suggest that cefadroxil and cefuroxime axetil share the same intestinal carrier.

Current therapeutical management, new antibiotics and treatment of Pseudomonas aeruginosa in bacterial ENT-infections

In bacterial infections of the sinuses and the middle ear Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus are most frequently isolated, whereas in tonsillopharyngitis Streptococcus pyogenes is the most important pathogen. S. aureus is found in up to 40 % in acute and chronic sinusitis and causes severe complications in otitis media, therefore antibiotics used as empirical initial treatment should also be effective against this pathogen. To decrease duration of illness and to avoid serious complications antibiotic treatment of bacterial ENT-infections is necessary. The new ketolides and the third and fourth generation quinolones are very effective and the second generation cephalosporins like cefuroxime axetil have proven excellent clinical and bacteriological efficacy in numerous clinical trials combined with an excellent resistance pattern over the years. Efficacy of short course therapy (5 days) in sinusitis and tonsillopharyngitis has been proven in clinical trials and is cost saving. In more severe infections treated in hospital sequential i. v./oral therapy offers pharmaco-economical benefits. Both regimen demonstrate cost savings while maintaining high clinical efficacy. In more severe infections like otitis externa diffusa, otitis externa maligna, otitis media chronica and perichondritis Pseudomonas aeruginosa is a dangerous pathogen that has to be covered by initial antibiotic treatment. Ciprofloxacin and Ceftazidime are widely used and effective. Ciprofloxacin resistance has increased, while Ceftazidime susceptibility is unchanged (> 90 %). A dose reduction study with ceftazidime in severe ENT-infections showed equivocal efficacy between 3 x 1 g and 3 x 2 g daily that offers a cost benefit of 50 %.

Levofloxacin: an updated review of its use in the treatment of bacterial infections.

Levofloxacin is the L-form of the fluoroquinolone antibacterial agent, ofloxacin. In in vitro studies, levofloxacin demonstrated a broad range of activity against Gram-positive and -negative organisms and anaerobes. The drug is more active against Gram-positive organisms than ciprofloxacin, but less active than newer fluoroquinolones such as gatifloxacin. Its activity against Streptococcus pneumoniae is unaffected by the presence of penicillin resistance. In several randomised controlled trails, 5 to 14 days' treatment with intravenous and/or oral levofloxacin proved an effective therapy for upper and lower respiratory tract infections. In patients with mild to severe community-acquired pneumonia (CAP), intravenous and/or oral levofloxacin 500mg once or twice daily was as effective as intravenous and/or oral gatifloxacin, clarithromycin, azithromycin or amoxicillin/clavulanic acid. Overall, clinical response rates with levofloxacin ranged from 86 to 95% versus 88 to 96% with comparator agents; bacteriological response rates were 88 to 95% and 86 to 98%, respectively. Sequential (intravenous +/- oral switch) therapy with levofloxacin 750mg once daily was as effective as intravenous imipenem/cilastatin (+/- oral switch to ciprofloxacin) in patients with severe nosocomial pneumonia. Generally, oral levofloxacin 250 or 500mg once daily was at least as effective as oral cefaclor, cefuroxime axetil, clarithromycin or moxifloxacin in patients with acute exacerbations of chronic bronchitis as assessed by either clinical or bacteriological response rates. This approach also provided similar efficacy to amoxicillin/ clavulanic acid or clarithromycin in patients with acute sinusitis. Sequential therapy with levofloxacin 500mg twice daily for 7 to 14 days' was as effective as intravenous imipenem/cilastatin in patients with suspected bacteraemia. Oral levofloxacin 500mg once daily for 7 to 10 days was also an effective treatment in patients with uncomplicated skin and skin structure infections, and in those with complicated urinary tract infections. A higher dosage of sequential levofloxacin 750mg once daily proved as effective as intravenous ticarcillin/clavulanic acid (+/- oral switch to amoxicillin/clavulanic acid) in the treatment of complicated skin and skin structure infections. Pharmacoeconomic studies suggest that levofloxacin may be cost-saving in comparison to conventional therapies. Levofloxacin continues to demonstrate good clinical efficacy in the treatment of a range of infections, including those in which S. pneumoniae is a potential pathogen. Importantly, it has efficacy in CAP similar to that of gatifloxacin and at least as good as that of the third generation cephalosporins. Extensive clinical data confirm the good tolerability profile of this agent without the phototoxicity, hepatic and cardiac events evident with some of the other newer fluoroquinolone agents. Levofloxacin therefore offers a unique combination of documented efficacy and tolerability, and provides an important option for the treatment of bacterial infections.