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Biomedical subjects

R Pauwels

Publications and source records attributed to R Pauwels.

At least 55 records · Page 3Linked to original sources
PubMed1998

Dual resistance to zidovudine and lamivudine in patients treated with zidovudine-lamivudine combination therapy: association with therapy failure.

Human immunodeficiency virus type 1 (HIV-1) strains dually resistant to zidovudine and lamivudine (3TC) may arise during zidovudine-3TC combination therapy. The objective of this cross-sectional study (n = 43 patients) was to test the association between therapy response (clinical and immunologic) to zidovudine-3TC and the level of phenotypic zidovudine resistance and zidovudine resistance-associated genotype of 3TC-resistant isolates. Other variables included were baseline CD4+ cell count, baseline Centers for Disease Control and Prevention (CDC) classification, virus load, and time receiving zidovudine. Phenotypic resistance was assessed using a recombinant virus assay. Genotypic analysis was based on population sequencing of plasma HIV-1. In a univariate analysis using a logistic regression model, it was found that therapy response was significantly associated with phenotypic and genotypic zidovudine resistance, baseline CD4+ cell count, and virus load. After adjustment for all variables, phenotypic resistance to zidovudine remained the only significantly associated factor, independent of baseline CD4+ cell count, baseline CDC classification, and virus load.

Anti-HIV Agents↗
PubMed1998

Patterns of resistance and cross-resistance to human immunodeficiency virus type 1 reverse transcriptase inhibitors in patients treated with the nonnucleoside reverse transcriptase inhibitor loviride.

Human immunodeficiency virus type 1 (HIV-1) strains resistant to nonnucleoside reverse transcriptase inhibitors (NNRTIs) may easily be selected for in vitro and in vivo under a suboptimal therapy regimen. Although cross-resistance is extensive within this class of compounds, newer NNRTIs were reported to retain activity against laboratory strains containing defined resistance-associated mutations. We have characterized HIV-1 resistance to loviride and the extent of cross-resistance to nevirapine, delavirdine, efavirenz, HBY-097, and tivirapine in a set of 24 clinical samples from patients treated with long-term loviride monotherapy by using a recombinant virus assay. Genotypic changes associated with resistance were analyzed by population sequencing. Overall, phenotypic resistance to loviride ranged from 0.04 to 3.47 log10-fold. Resistance was observed in samples from patients who had discontinued loviride for up to 27 months. Cross-resistance to the other compounds was extensive; however, fold resistance to efavirenz was significantly lower than fold resistance to nevirapine. No genotypic changes were detected in three samples; these were sensitive to all of the NNRTIs tested. The most common genotypic change was the K103N substitution. The range of phenotypic resistance in samples containing the K103N substitution could not be predicted from a genotypic analysis of known NNRTI resistance-associated mutations. The Y181C substitution was detected in one isolate which was resistant to loviride and delavirdine but sensitive to efavirenz, HBY-097, and tivirapine. Our data indicate that the available newer NNRTIs which retain activity against some HIV-1 strains selected by other compounds of this class in vitro may have compromised clinical efficacy in some patients pretreated with NNRTI.

Acetamides↗
PubMed1998

A rapid method for simultaneous detection of phenotypic resistance to inhibitors of protease and reverse transcriptase in recombinant human immunodeficiency virus type 1 isolates from patients treated with antiretroviral drugs.

Combination therapy with protease (PR) and reverse transcriptase (RT) inhibitors can efficiently suppress human immunodeficiency virus (HIV) replication, but the emergence of drug-resistant variants correlates strongly with therapeutic failure. Here we describe a new method for high-throughput analysis of clinical samples that permits the simultaneous detection of HIV type 1 (HIV-1) phenotypic resistance to both RT and PR inhibitors by means of recombinant virus assay technology. HIV-1 RNA is extracted from plasma samples, and a 2.2-kb fragment containing the entire HIV-1 PR- and RT-coding sequence is amplified by nested reverse transcription-PCR. The pool of PR-RT-coding sequences is then cotransfected into CD4+ T lymphocytes (MT4) with the pGEMT3deltaPRT plasmid from which most of the PR (codons 10 to 99) and RT (codons 1 to 482) sequences are deleted. Homologous recombination leads to the generation of chimeric viruses containing PR- and RT-coding sequences derived from HIV-1 RNA in plasma. The susceptibilities of the chimeric viruses to all currently available RT and/or PR inhibitors is determined by an MT4 cell-3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide-based cell viability assay in an automated system that allows high sample throughput. The profile of resistance to all RT and PR inhibitors is displayed graphically in a single PR-RT-Antivirogram. This assay system facilitates the rapid large-scale phenotypic resistance determinations for all RT and PR inhibitors in one standardized assay.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Influence of treatment on the nose and/or the lungs.

The association of rhinitis and asthma in the same patient is frequent and requires an appropriate treatment strategy. Several studies have investigated the effect of antirhinitis treatment on concurrent asthma symptoms and pathophysiology. Most of these studies have been performed in patients with seasonal allergic rhinitis and asthma. Treatment with intranasal corticosteroids during the pollen season decreases asthma symptoms and prevents the increase in non-allergic bronchial hyperresponsiveness in patients with a combination of rhinitis and asthma symptoms. This treatment also inhibits the increase in bronchial hyperresponsiveness in patients with rhinitis symptoms alone. The observation that treatment with intranasal corticosteroids reduces non-allergic bronchial hyperresponsiveness in patients with rhinitis is remarkable and will stimulate thought about the mode of action of these drugs. Intranasal sodium cromoglycate has also been studied and, although effective, has been shown to be less effective than intranasal corticosteroids in controlling the accompanying asthma symptoms in patients with seasonal allergic rhinitis and asthma. Treatment with antihistamines also reduced the symptoms of rhinitis and asthma during the pollen season. However, the optimal therapy for patients with a history of seasonal allergic rhinitis and asthma remains to be established. Few data are available on the effect of treatment for perennial allergic rhinitis on perennial asthma. The rather frequent combination of rhinitis and asthma therefore warrants further study.

Adrenal Cortex Hormones↗
PubMed1997

Serum neuron-specific enolase as a tumor marker in the diagnosis and follow-up of small-cell lung cancer.

Serum samples for the determination of neuron-specific enolase (NSE) levels were collected at diagnosis, after induction of chemotherapy and at relapse in order to assess the value of NSE in the diagnosis and management of small-cell lung cancer (SCLC). At diagnosis, 47 of 64 patients with SCLC (73%) had abnormal NSE values (i.e. NSE > 12.5 micrograms/l). Mean NSE values were significantly higher in patients with extensive disease compared to limited disease. Patients with other malignancies or benign lung diseases presented with elevated NSE levels in approximately 15 and 4% of cases. Sensitivity, specificity and predictive value of positive results of NSE at diagnosis were 74, 83 and 71%, respectively, for a cutoff value of 12.5 micrograms/l. In responders mean NSE dropped significantly from 46.1 micrograms/l before chemotherapy to 17.0 micrograms/l after three cycles of chemotherapy. Nonresponders as a group showed a nonsignificant drop. At relapse mean NSE increased from 6.5 micrograms/l at the time of response to 51.9 micrograms/l at the time of progression, but in 5 of the 18 evaluable patients normal levels persisted. Thus, evolution of NSE in patients receiving chemotherapy correlated well with tumor volume in patients who responded, but often failed to predict a therapeutic outcome in patients with apparently chemoresistant tumor (i.e. some nonresponders showed a decrease in NSE levels). A similar lack of correlation between NSE levels and tumor volume was seen at the time of relapse. We conclude that the determination of NSE levels is of doubtful utility in the diagnosis and follow-up of SCLC patients.

Adult↗
PubMed1997

Airway deposition and airway effects of antiasthma drugs delivered from metered-dose inhalers.

Many different metered-dose inhalation devices are becoming available for the treatment of airway diseases. Each of these inhalers differs in its delivery characteristics. An assessment of the efficacy of drug delivery by these inhalers is essential, in view of their therapeutic use. A review of the literature on the relationship between airway deposition and airway effects of drugs delivered from metered-dose inhalers is presented. Nebulizers or spacers are not discussed. The effect of an inhaler depends on the characteristics of the inhaler and the inhalation manoeuvre performed by the patient. This review focuses on the influence of inhaler characteristics on the airway deposition and airway effects. Data from several studies show that there is a significant relationship between the amount of drug deposited in the airways and the airway effects of the drug. Studies on the relationship between airway deposition and airway effect have been troubled by methodological problems, such as the absence of multiple dose comparisons and the difficulty in obtaining steep dose-response curves. The techniques for measuring airway deposition of inhaled drugs, namely the scintigraphic and the pharmacokinetic method, are discussed and compared. The appropriate use of these techniques can help to define and compare the drug delivery characteristics of different devices, thus enabling inhaled therapy to be optimized.

Administration, Inhalation↗
PubMed1996

Crystal structures of 8-Cl and 9-Cl TIBO complexed with wild-type HIV-1 RT and 8-Cl TIBO complexed with the Tyr181Cys HIV-1 RT drug-resistant mutant.

Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) is an important target for chemotherapeutic agents used in the treatment of AIDS; the TIBO compounds are potent non-nucleoside inhibitors of HIV-1 RT (NNRTIs). Crystal structures of HIV-1 RT complexed with 8-Cl TIBO (R86183, IC50 = 4.6 nM) and 9-Cl TIBO (R82913, IC50 = 33 nM) have been determined at 3.0 A resolution. Mutant HIV-1 RT, containing Cys in place of Tyr at position 181 (Tyrl81Cys), is highly resistant to many NNRTIs and HIV-1 variants containing this mutation have been selected in both cell culture and clinical trials. We also report the crystal structure of Tyrl81Cys HIV-1 RT in complex with 8-Cl TIBO (IC50 = 130 nM) determined at 3.2 A resolution. Averaging of the electron density maps computed for different HIV-1 RT/NNRTI complexes and from diffraction datasets obtained using a synchrotron source from frozen (-165 degrees C) and cooled (-10 degrees C) crystals of the same complex was employed to improve the quality of electron density maps and to reduce model bias. The overall locations and conformations of the bound inhibitors in the complexes containing wild-type HIV-1 RT and the two TIBO inhibitors are very similar, as are the overall shapes and volumes of the non-nucleoside inhibitor-binding pocket (NNIBP). The major differences between the two wild-type HIV-1 RT/TIBO complexes occur in the vicinity of the TIBO chlorine substituents and involve the polypeptide segments around the beta5-beta6 connecting loop (residues 95 to 105) and the beta13-beta14 hairpin (residues 235 and 236). In all known structures of HIV-1 RT/NNRTI complexes, including these two, the position of the beta12-beta13 hairpin or the "primer grip" is significantly displaced relative to the position in the structure of HIV-1 RT complexed with a double-stranded DNA and in unliganded HIV-1 RT structures. Since the primer grip helps to position the template-primer, this displacement suggests that binding of NNRTIs would affect the relative positions of the primer terminus and the polymerase active site. This could explain biochemical data showing that NNRTI binding to HIV-1 RT reduces efficiency of the chemical step of DNA polymerization, but does not prevent binding of either dNTPs or DNA. When the structure of the Tyr181Cys mutant HIV-1 RT in complex with 8-Cl TIBO is compared with the corresponding structure containing wild-type HIV-1 RT, the overall conformations of Tyr181Cys and wild-type HIV-1 RT and of the 8-Cl TIBO inhibitors are very similar. Some positional changes in the polypeptide backbone of the beta6-beta10-beta9 sheet containing residue 181 are observed when the Tyr181Cys and wild-type complexes are compared, particularlty near residue Val179 of beta9. In the p51 subunit, the Cys181 side-chain is oriented in a similar direction to the Tyr181 side-chain in the wild-type complex. However, the electron density corresponding to the sulfur of the Cys181 side-chain in the p66 subunit is very weak, indicating that the thiol group is disordered, presumably because there is no significant interaction with either 8-Cl TIBO or nearby amino acid residues. In the mutant complex, there are slight rearrangements of the side-chains of other amino acid residues in the NNIBP and of the flexible dimethylallyl group of 8-Cl TIBO; these conformational changes could potentially compensate for the interactions that were lost when the relatively large tyrosine at position 181 was replaced by a less bulky cysteine residue. In the corresponding wild-type complex, Tyr181 iin the p66 subunit has significant interactions with the bound inhibitor and the position of the Tyr181 side-chain is well defined in both subunits. Apparently the Tyr181 --> Cys mutation eliminates favorable contacts of the aromatic ring of the tyrosine and the bou

Antiviral Agents↗
PubMed1996

Antiviral effects of milk proteins: acylation results in polyanionic compounds with potent activity against human immunodeficiency virus types 1 and 2 in vitro.

A number of native and modified milk proteins from bovine or human sources were analyzed for their inhibitory effects on human immunodeficiency virus type 1 (HIV-1) and HIV-2 in vitro in an MT4 cell test system. The proteins investigated were lactoferrin, alpha-lactalbumin, beta-lactoglobulin A, and beta-lactoglobulin B. By acylation of the amino function of the lysine residues in the proteins, using anhydrides of succinic acid or cis-aconitic acid, protein derivatives were obtained that all showed a strong antiviral activity against human immunodeficiency virus type 1 and/or 2. The in vitro IC50 values of the aconitylated proteins were in the concentration range of 0.3 to 3 nM. Succinylation or aconitylation of alpha-lactalbumin and beta-lactoglobulin A/B also produced strong anti-HIV-2 activity with IC50 values on the order 500 to 3000 nM. All compounds showed virtually no cytotoxicity at the concentration used. Peptide-scanning studies indicated that the native lactoferrin as well as the charged modified proteins strongly bind to the V3 loop of the gp120 envelope protein, with Kd values in the same concentration range as the above-mentioned IC50. Therefore, shielding of this domain, resulting in inhibition of virus-cell fusion and entry of the virus into MT4 cells, may be the likely underlying mechanism of antiviral action.

Aconitic Acid↗
PubMed1996

Mechanism of anti-HIV activity of negatively charged albumins: biomolecular interaction with the HIV-1 envelope protein gp120.

A novel class of polyanionic proteins with potent anti-human immunodeficiency virus type 1 activity, the negatively charged albumins (NCAs), have been reported previously. In vitro antiviral assays established that these compounds preferentially inhibit virus-cell fusion and syncytium formation and that virus-cell binding is less affected. Here the interaction of the NCAs with synthetic peptides composed of 15-36 amino acids and corresponding to different parts of the gp120 envelope protein is described. Among the gp120 peptides tested, binding of the NCAs was observed only with the s0-called V3 loop (amino acids 296-330) and the C-terminal part of gp120. A higher number of negatively charged residues in the albumins resulted in higher binding affinities. NCAs in which, in addition to negative charges, up to 7 or 14 lactose or mannose groups were introduced, respectively did not exhibit increasing binding affinity. In contrast, mannosylated albumin containing about 14 mannose groups showed an increased binding compared with native albumin. Binding of the NCAs to the V3 and C-terminal oligopeptide was competitively inhibited by sulfated polysaccharide heparin and dextran sulfate. This finding indicates that the binding between the gp120 peptides and the NCAs is likely caused by electrostatic interactions. However, the fact that the dissociation constants of dextran sulfate and heparin are orders of magnitude larger compared with the NCAs indicates that the spatial structure of the proteins and/or hydrophobic interactions between the NCAs and the envelope protein may also be involved.

Albumins↗
PubMed1996

Betulinic acid derivatives: a new class of specific inhibitors of human immunodeficiency virus type 1 entry.

A novel series of omega-aminoalkanoic acid derivatives of betulinic acid were synthesized and evaluated for their activity against human immunodeficiency virus (HIV). The anti-HIV-1 activity of several members of this new series was found to be in the nanomolar range in CEM 4 and MT-4 cell cultures. The optimization of the omega-aminoalkanoic acid side chain is described. The presence of an amide function within the side chain was found important for optimal activity. RPR 103611 (14g), a statine derivative, was found to be inactive against HIV-1 protease, reverse transcriptase, and integrase as well as on gp120/CD4 binding. "Time of addition" experiments suggested interaction with an early step of HIV-1 replication. As syncytium formation, but not virus-cell binding, seems to be affected, betulinic acid derivatives are assumed to interact with the postbinding virus-cell fusion process.

Antiviral Agents↗
PubMed1996

Betulinic acid derivatives: a new class of human immunodeficiency virus type 1 specific inhibitors with a new mode of action.

A series of omega-undecanoic amides of lup-20(29)-en-28-oic acid derivatives were synthesized and evaluated for activity in CEM 4 and MT-4 cell cultures against human immunodeficiency virus type 1 (HIV-1) strain IIIB/LAI. The potent HIV inhibitors which emerged, compounds 5a, 16a, and 17b, were all derivatives of betulinic acid (3beta-hydroxylup-20(29)-en-28-oic acid). No activity was found against HIV-2 strain ROD. Compound 5a showed no inhibition of HIV-1 reverse transcriptase activity with poly(C).oligo(dG) as template/primer, nor did it inhibit HIV-1 protease. Additional mechanistic studies revealed that this class of compounds interfere with HIV-1 entry in the cells at a postbinding step.

Antiviral Agents↗
PubMed1996

Development of vaginal microbicides for the prevention of heterosexual transmission of HIV.

Various compounds could be considered to be vaginal microbicides, preventing heterosexual transmission of HIV (i.e. virucidal agents such as nonoxynol 9 and chlorhexidine) and antiviral agents interfering with either virus adsorption/fusion [polyanionic substances such as polysulfates (i.e. PVAS, PAVAS), polysulfonates, polycarboxylates, polyoxometalates and negatively charged albumins], or fusion/uncoating (bicyclams), or reverse transcription [dideoxynucleoside analogues, acyclic nucleoside phosphonates such as PMEA and PMPA, and non-nucleoside reverse transcriptase inhibitors (NNRTIs) such as TIBO, HEPT, and alpha-APA derivatives]. In particular, combination of two or more of these compounds seems to be an attractive approach to interrupt transmission of HIV at different stages of the infectious process.

Administration, Intravaginal↗
PubMed1996

Preparation and characterization of conjugates of (modified) human serum albumin and liposomes: drug carriers with an intrinsic anti-HIV activity.

Human serum albumin (HSA) derivatized with cis-aconitic anhydride (Aco-HSA) that was earlier shown to inhibit replication of human immunodeficiency virus type 1 (HIV-1), was covalently coupled to conventional liposomes, consisting of phosphatidylcholine, cholesterol and maleimido-4-(p-phenylbutyryl)phosphatidylethanolamine, using the heterobifunctional reagent N-succinimidyl-S-acetylthioacetate (SATA). The amount of HSA that could be coupled to the liposomes depended on derivatization of the HSA and ranged from 64.2 +/- microgram HSA/micromol total lipid for native HSA to 29.5 +/- 2.7 microgram HSA/micromol total lipid for HSA in which 53 of the epsilon amino groups of lysine were derivatized with cis-aconitic anhydride (Aco53-HSA). Incorporation of 3.8 mol% of total lipid of a poly(ethylene glycol) derivative of phosphatidylethanolamine (PEG-PE) in the liposomes resulted in a lower coupling efficiency of Aco-HSA. The elimination and distribution of the liposomal conjugates in rats in vivo was largely dependent on the modification of the HSA coupled to the liposomes. With native HSA-liposomes, more than 70% of the conjugate was still found in the blood plasma 30 min after i.v. injection in rats, while at this time Aco-HSA-liposomes were completely cleared from the circulation. The rapid clearance of conventional Aco-HSA-liposomes was due to a rapid uptake into the liver and could be considerably decreased by incorporating PEG-PE in the liposomal bilayer. After 3 h 60% of Aco-HSA-PEG-liposome conjugates were found in the blood. In an in vitro anti-HIV-1 assay, the 50% inhibitory concentrations (IC50) for Aco39-HSA-liposomes and Aco53-HSA-liposomes expressed as protein weight, were 2.87 microgram/ml and 0.154 microgram/ml, respectively. When PEG-PE was incorporated, the Aco53-HSA-liposomes retained anti HIV-1 activity (IC50:3.13 microgram/ml). The possibility to modulate the residence time in the bloodstream of Aco-HSA-liposomes and the potent anti-HIV-1 activity of these conjugates, may allow the development of an intrinsically active drug carrier system. By incorporating anti HIV-1 drugs such as AZT into such liposomes a drug delivery system can be designed that might act simultaneously on the virus/cell binding by virtue of the coupled Aco-HSA and on the RNA/DNA transcription of the HIV-1 replication cycle through the nucleoside analogue.

Aconitic Acid↗
PubMed1996

Synthesis and structure-activity relationships of phenylenebis(methylene)-linked bis-tetraazamacrocycles that inhibit human immunodeficiency virus replication. 2. Effect of heteroaromatic linkers on the activity of bicyclams.

A series of bicyclam analogs connected through a heteroaromatic linker have been synthesized and evaluated for their inhibitory effects on HIV-1 (IIIB) and HIV-2 (ROD) replication in MT-4 cells. The activity of pyridine- and pyrazine-linked bicyclams was found to be highly dependent upon the substitution of the heteroaromatic linker connecting the cyclam rings. For example, 2,6- and 3,5-pyridine-linked bicyclams were potent inhibitors of HIV-1 and HIV-2 replication, whereas the 2,5- and 2,4-substituted pyridine-linked compounds exhibited substantially reduced activity and, in addition, were found to be highly toxic to MT-4 cells. We have subsequently discovered that these effects are not unique; amino-substituted linkers also have the potential to deactivate phenylenebis(methylene)-linked bicyclams. A model is proposed to explain the deactivating effects of the pyridine group in certain substitution patterns based on the ability of the pyridine nitrogen to participate in pendant conformations (complexation) with the adjacent azamacrocyclic ring, which may involve hydrogen bonding or coordination to a transition metal. The introduction of a sterically hindering group such as phenyl at the 6-position of the 2,4-substituted pyridine-linked bicyclam appears to prevent pendant conformations, providing an analog with comparable anti-HIV-1 and anti-HIV-2 activities to the parent m-phenylenebis(methylene)-linked bicyclam. The results of this study have been used to develop a quantitative structure-activity relationship model with improved predictive capability in order to aid the design of antiviral bis-azamacrocyclic analogs.

Antiviral Agents↗
PubMed1996

New arylpyrido-diazepine and -thiodiazepine derivatives are potent and highly selective HIV-1 inhibitors targeted at the reverse transcriptase.

A series of pyridobenzothiodiazepindioxides such as the 11-ethyl-6,8,9-trimethyl-6,11-dihydro-pyrido[2,3-f] [2,1,5]benzothiodiazepine-5,5-dioxide and arylpiridodiazepines such as the 6,7-dihydro-7-methyl-12-ethyl-pyrido[2,3-b] pyrido(2',3'-4,5]furo[2,3-f][1,4]diazepin-6(12H)-thio and the 6,7-dihydro-7-methyl-12-ethyl-pyrido[2,3-b]pyrido- [2,3-4,5]thieno[2,3-f][1,4] diazepin-6(12H)-thione were found to inhibit human immunodeficiency virus type 1 [HIV-1(IIIB)] replication at a concentration of 0.003-0.04 microM without being cytotoxic at a 3,000- to 15,000-fold higher concentration. These compounds proved effective against a variety of HIV-1 strains, including those that are resistant to 3'-azido-3' deoxythymidine (AZT), but not against HIV-2, simian immunodeficiency virus or herpes simplex virus. An HIV-1 strain containing the 188 Tyr-->His mutation in the reverse transcriptase displayed severely reduced sensitivity to the compounds. The specificity of these compounds is due to an interaction with the reverse transcription process. The 6,7-dihydro-7-methyl-12-ethyl-pyrido[2,3-b]pyrido [2,3-4,5]thieno[2,3-f][1,4]diazepin-6(12H)-thione (MEN 10979) enhanced the anti-HIV-1 activity of AZT and dideoxyinosine (ddI) in a synergistic manner. The new arylpyrido-diazepine and -thiodiazepine derivatives appear to be drug candidates for the treatment of HIV-1 infection.

Antiviral Agents↗
PubMed1996

Comparative safety and efficacy of sparfloxacin in the treatment of acute exacerbations of chronic obstructive pulmonary disease: a double-blind, randomised, parallel, multicentre study.

In a double-blind, placebo-controlled trial, patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) were randomly allocated to oral treatment with sparfloxacin (200 mg loading dose followed by 100 mg once daily) or amoxycillin/clavulanic acid (500 mg/125 mg tds) for a total treatment duration of 7 to 14 days. Patients were evaluable if they had a FEV1/FVC ratio of less than 70% at stable state and presented with a suspected infectious exacerbation defined as increases in dyspnoea, sputum volume and sputum purulence. The primary efficacy variable was the overall success (defined as disappearance or improvement of dyspnoea and reductions in sputum volume and purulence) at end of treatment and follow-up. Overall efficacy was assessed in both the intent-to-treat (728 patients) and the evaluable (351 patients) populations. At the end of treatment and follow-up, success rates were identical for the sparfloxacin (87.3% and 78.7%) and amoxycillin-clavulanic acid (88.8% and 79.8%) treatment groups. Similar figures were found for the intent-to-treat population. The analysis of drug safety was similar for both treatment groups. The most frequently encountered pathogens were Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Sparfloxacin appeared superior for bacteriological eradication of Haemophilus influenzae, and Moraxella catarrhalis. Sparfloxacin in a single daily dose appears at least as effective as amoxycillin/clavulanic acid in the treatment of patients with acute exacerbations of COPD.

Acute Disease↗