Iclaprim reduces the incidence and severity of Staphylococcus aureus-induced septic arthritis in a murine model.

Staphylococcus aureus is the most common non-gonococcal aetiology of septic arthritis. The efficacy of iclaprim against S. aureus LS-1, a clinical strain identified from a patient with septic arthritis, was studied in MF1 mice to evaluate the activity of iclaprim, which is in clinical development, in preventing joint infections. Iclaprim (2.5-80 mg kg- 1) administered as a single dose via the tail vein reduced the incidence of S. aureus septic arthritis and mortality in an experimental murine model of septic arthritis.

Telavancin shows superior activity to vancomycin with multidrug-resistant Staphylococcus aureus in a range of in vitro biofilm models.

The activity of telavancin was compared with vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) in planktonic culture and biofilms grown using a range of in vitro models. Antibiotic efficacy was determined using 24 clinical isolates, including healthcare-associated (HA)-MRSA, community-associated (CA)-MRSA and isolates with reduced (intermediate) susceptibility to vancomycin (VISA). Activity against biofilms was compared using three models: 96-peg plates, 96-well flat-bottom plates and a flow-cell system. Cell death was evaluated using a metabolic dye and Live/Dead staining. The planktonic minimum inhibitory concentration (MIC) range for telavancin was lower than that for vancomycin (0.06-0.25 mg/l and 0.5-8 mg/l, respectively). Vancomycin (100 × MIC) killed, on average, 59% of cells in HA-MRSA biofilms grown on 96-peg plates, 44% of cells in CA-MRSA biofilms and 26% of cells in VISA biofilms. Telavancin (100 × MIC) killed, on average, 63%, 49% and 41% of cells, respectively. The antibiotics showed similar efficacy against MRSA biofilms but telavancin was more effective against those formed by VISA isolates. In the flow-cell system, antibiotic cell killing was enhanced with both antibiotics, killing up to 80% of biofilm-associated cells. The variance in cell killing displayed when biofilms were grown using different systems highlights the importance of selecting an appropriate model for antimicrobial efficacy tests. The flow-cell system more closely reflects conditions encountered during infection and is possibly more clinically relevant than a 96-well plate system. Despite differences between the models evaluated, telavancin typically demonstrated improved efficacy over vancomycin, indicating the potential value of the agent in the treatment of biofilm-mediated infections caused by S. aureus, especially multidrug-resistant isolates.

Surface disinfection properties of the combination of an antimicrobial peptide, ranalexin, with an endopeptidase, lysostaphin, against methicillin-resistant Staphylococcus aureus (MRSA).

AIMS: To characterize the antibacterial synergy of the antimicrobial peptide, ranalexin, used in combination with the anti-staphylococcal endopeptidase, lysostaphin, against methicillin-resistant Staphylococcus aureus (MRSA), and to assess the combination's potential as a topical disinfectant or decolonizing agent for MRSA. MRSA causes potentially lethal infections, and pre-operative patients colonized with MRSA are often treated with chlorhexidine digluconate and mupirocin cream to eradicate carriage. However, chlorhexidine is unsuitable for some patients, and mupirocin resistance is increasingly encountered, indicating new agents are required. METHODS AND RESULTS: Using an ex vivo assay, ranalexin and lysostaphin tested in combination reduced viable MRSA on human skin to a greater extent than either compound individually. The combination killed bacteria within 5 min and remained effective and synergistic even in high salt and low pH conditions. CONCLUSIONS: The combination is active against MRSA on human skin and under conditions that may be encountered in sweat. SIGNIFICANCE AND IMPACT OF THE STUDY: Although the exact mechanism of activity remains unresolved, considering its specific spectrum of activity, fast killing kinetics and low likelihood of resistance arising, the combination of ranalexin with lysostaphin warrants consideration as a new agent to eradicate nasal and skin carriage of Staph. aureus, including MRSA.

Usefulness of mec-associated direct repeat unit (dru) typing in the epidemiological analysis of highly clonal methicillin-resistant Staphylococcus aureus in Scotland.

The incidence of the epidemic methicillin-resistant Staphylococcus aureus (EMRSA) strains EMRSA-15 and EMRSA-16 in Scotland has increased dramatically, now accounting for c. 70% and c. 20% of isolates, respectively. Epidemiological tracking of these EMRSA strains is difficult, as c. 50% of EMRSA-15 and c. 35% of EMRSA-16 isolates are indistinguishable using pulsed-field gel electrophoresis (PFGE) and other typing methods. The usefulness of mec-associated direct repeat unit (dru) sequence analysis as a more sensitive approach to tracking the persistence and spread of these 'clonal' EMRSA strains in Scotland was evaluated. Analysis of 47 EMRSA-15 and 57 EMRSA-16 isolates (including two separately cultured isolates of the Harmony collection type strain) obtained from 22 hospital laboratories over an 8-year period (1997-2005) revealed 13 and 12 different dru types, respectively. Whereas some types appeared to be endemic in multiple hospitals, subtypes that may represent specific strain movement among hospitals in a given geographical region were identified in other instances. These results suggest that mec-associated dru typing may have potential for identifying and tracking specific subtypes of otherwise indistinguishable epidemic MRSA isolates such as those in Scotland.

Antimicrobial susceptibility testing of Actinomyces species with 12 antimicrobial agents.

OBJECTIVE: This study was conducted to assess the susceptibility of human clinical isolates of Actinomyces species to 12 antimicrobial agents. METHODS: Human clinical isolates of Actinomyces spp. were collected from stored collections held at the Microbiology Department, Edinburgh University, Anaerobe Reference Laboratory, Cardiff, Glasgow Dental Hospital and Glasgow Royal Infirmary. Each isolate was identified by restriction analysis of amplified 16S ribosomal DNA. MICs of 12 antibiotics comprising benzyl penicillin, amoxicillin, ceftriaxone, linezolid, tetracycline, deoxycycline, clindamycin, erythromycin, clarithromycin, ciprofloxacin, meropenem and piperacillin/tazobactam for 87 strains of Actinomyces species were obtained by Etest methodology. RESULTS: The Actinomyces species identified for this study comprised: Actinomyces israelii, Actinomyces gerencseriae, Actinomyces turicensis, Actinomyces funkei, Actinomyces graevenitzii and Actinomyces europaeus. All isolates were susceptible to penicillin and amoxicillin. All but one strain of A. turicensis was susceptible to linezolid. A number of A. europaeus and A. graevenitzii isolates were resistant to ceftriaxone and piperacillin/tazobactam. A number of isolates of A. turicensis and A. europaeus also demonstrated resistance to erythromycin. All Actinomyces species tested appeared resistant to ciprofloxacin. CONCLUSIONS: Actinomyces species appear to be susceptible to a wide range of beta-lactam agents and these, when combined with beta-lactamase inhibitors, should be regarded as agents of first choice. Ciprofloxacin performed poorly. Tetracyclines also demonstrated poor performance. This is the first study of antimicrobial susceptibilities for a number of accurately identified clinical isolates of Actinomyces spp. There are a number of species differences in susceptibility profiles to the antimicrobials tested, suggesting that accurate identification and speciation may have an impact on clinical outcome.

Gingivitis and toothbrushes: potential roles in viridans streptococcal bacteraemia.

We report a case of Streptococcus oralis bacteraemia in a paediatric neutropenic patient with acute myeloid leukaemia whose predominant form of oral compromise was severe gingivitis, rather than mucositis. By phenotypic and genotypic analyses, the strain of S. oralis from blood culture was indistinguishable from an isolate from his mouth, suggesting that gingivitis may have provided a portal of entry for viridans streptococci into the bloodstream. To improve the patient's oral and dental hygiene and reduce gingivitis, conventional disposable foam toothettes were substituted with a new soft toothbrush for use as part of the oral care protocol. As there are no guidelines regarding the frequency of replacement of toothbrushes used by immunocompromised patients, the brush was swabbed regularly and culture performed to detect microbial colonization. Viridans streptococci were cultured from the toothbrush after 2 weeks of use. Phenotypic, followed by genotypic analyses, demonstrated that a strain of S. oralis from the toothbrush was indistinguishable from the strain previously isolated from blood culture and mouth. Soft toothbrushes may be useful tools for maintaining oral hygiene in immunocompromised individuals. However the results of this study indicate that regular replacement is warranted, as the toothbrush itself may become colonized with the organisms responsible for bacteraemia.

Bacteriostatic activity of human lactoferrin against Staphylococcus aureus is a function of its iron-binding properties and is not influenced by antibiotic resistance.

The in vitro antistaphylococcal activity of lactoferrin and the antibiotic resistance of clinical Staphylococcus aureus isolates obtained from three different sites of infection were examined. Antibiotic, but not lactoferrin resistance correlated with selective antibiotic pressure, and nosocomial and most community isolates were antibiotic resistant, whereas only a third of each group was resistant to lactoferrin. The antimicrobial activity of lactoferrin, both in defined medium and in normal human plasma serum, was dependent upon its ferrochelating properties. Therapeutic approaches based on the use of ferrochelating agents such as lactoferrin combined with antimicrobial drugs may help to counteract the reduced efficacy of current antibiotics.

Putative virulence factor expression by clinical and food isolates of Bacillus spp. after growth in reconstituted infant milk formulae.

Forty-seven strains representing 14 different Bacillus species isolated from clinical and food samples were grown in reconstituted infant milk formulae (IMF) and subsequently assessed for adherence to, invasion of, and cytotoxicity toward HEp-2 and Caco-2 cells. Cell-free supernatant fluids from 38 strains (81%) were shown to be cytotoxic, 43 strains (91%) adhered to the test cell lines, and 23 strains (49%) demonstrated various levels of invasion. Of the 21 Bacillus cereus strains examined, 5 (24%) were invasive. A larger percentage of clinically derived Bacillus species (20%) than of similar species tested from the food environment were invasive. Increased invasion occurred after growth of selected Bacillus species in reconstituted IMF containing glucose. While PCR primer studies revealed that many different Bacillus species contained DNA sequences encoding the hemolysin BL (HBL) enterotoxin complex and B. cereus enterotoxin T, not all of these isolates expressed these diarrheagenic genes after growth in reconstituted IMF. Of the 47 Bacillus isolates examined, 3 isolates of B. cereus and 1 isolate of B. subtilis produced the HBL enterotoxin after 18 h of growth in brain heart infusion broth. However, eight isolates belonging to the species B. cereus, B. licheniformis, B. circulans, and B. megaterium were found to produce this enterotoxin after growth in reconstituted IMF when assessed with the B. cereus enterotoxin (diarrheal type) reversed passive latex agglutination (RPLA) kit. It is concluded that several Bacillus species occurring occasionally in clinical specimens and food samples are of potential medical significance due to the expression of putative virulence factors.

Susceptibility of a variety of clinical isolates to linezolid: a European inter-country comparison.

Using standardized in vitro susceptibility tests, 3382 bacteria recently isolated from skin, blood or respiratory tract infections were analysed for their susceptibility to linezolid, a new oxazolidinone, and a number of comparator antibacterial agents. Isolates originated in France, Italy, Germany, Spain, Sweden, The Netherlands and the UK. Laboratories in each country independently conducted broth microdilution susceptibility tests using NCCLS methods and epsilonometry (Etest). Isolates of Gram-positive cocci tested in each laboratory included methicillin-susceptible and -resistant Staphylococcus aureus, methicillin-susceptible and -resistant Staphylococcus epidermidis, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus pneumoniae and Enterococcus spp. Isolates of Moraxella catarrhalis and Haemophilus influenzae were also included. Where appropriate, comparator drugs (oxacillin, vancomycin, gentamicin, co-amoxiclav, ciprofloxacin, erythromycin, penicillin G, clindamycin and ampicillin) were also tested. Linezolid demonstrated excellent activity against all of the Gram-positive cocci with MIC50s ranging from 0.5 to 4 mg/L. The drug demonstrated only modest activity against M. catarrhalis and H. influenzae with MIC50s ranging from 4 to 16 mg/L.

Antimicrobial susceptibility of blood culture isolates of viridans streptococci: relationship to a change in empirical antibiotic therapy in febrile neutropenia.

This study investigated the antibiotic susceptibilities of 67 isolates of viridans streptococci from 61 cases of bacteraemia in immunocompromised paediatric patients with malignancy. The majority of patients (87%) had received prior courses of empirical antibiotic therapy, which consisted of ceftazidime plus amikacin during period 1 and piperacillin/tazobactam plus amikacin during period 2. Susceptibility to vancomycin and quinupristin/dalfopristin was 100%. Susceptibility to beta-lactam antibiotics varied. For period 1, the geometric mean MICs of all beta-lactams tested against blood culture isolates (n = 31) exceeded those against isolates (n = 36) collected from blood after the change in empirical therapy (by 3.3-fold for ceftazidime, 2.8-fold for piperacillin/tazobactam and 1.6-fold for penicillin). The selection of a beta-lactam antibiotic for empirical therapy must be made with care, as repeated courses of certain agents may be more likely to select for viridans streptococci with diminished susceptibility.

Emerging concepts in the management of the malignant haematological disorders.

A comprehensive review of novel cytoreductive agents is presented. Such novel agents may be found among chemical compounds directed against specific molecular targets (cytostatics) or within the biological substances selectively aimed at the malignant clone (immunotherapy). It is stated that the purposes of immunotherapy in general are to generate a T-lymphocytic response against the tumour cells, e.g., graft versus leukaemia (GvL) effect, natural killer T-cell cytolysis, antibody-dependent cytolysis etc.; or to reprogramme the immune system of the tumour-bearing host by DNA and/or RNA manipulation with subsequent interference with the signalling pathway in the tumour cells. Some immunotherapeutic modalities are shortly described: donor T-lymphocyte infusion and GvL effect, polyclonal antibodies, monoclonal antibodies, vaccines, gene replacement therapy, suicide gene therapy, antisense oligonucleotides, alterations of DNA-RNA transcript factors and malignant antigenic drive etc. Most likely, a sequence of different treatment modalities will be used in the future comprising an initial debulking by means of standard chemotherapy and/or irradiation followed by target unspecific immunotherapy (polyclonal immunoglobulins, GvL effect etc.) and finally target specific elimination of residual tumour, probably with repeated use of the minimum effective pharmacologic dose (MEPD) of the agents used. In contrast, the current use of high-dose myeloablative chemotherapy with the use of maximum tolerable dose (MTD) and associated severe organ toxicity, and high rates of secondary malignancies will probably be substituted in the future. An effective supportive treatment will be highly necessary, especially related to prevention and treatment of infections.

Origins of Staphylococcus epidermidis and Streptococcus oralis causing bacteraemia in a bone marrow transplant patient.

Coagulase-negative staphylococcal bacteraemia in immunocompromised patients is often associated with the use of central venous catheters, while the proposed origin of viridans streptococci causing bacteraemia in this patient group is the oral cavity. This report describes an episode of polymicrobial bacteraemia caused by Staphylococcus epidermidis and Streptococcus oralis followed by several further episodes of S. epidermidis bacteraemia in a 15-year-old boy after bone marrow transplantation. Pulsed-field gel electrophoresis (PFGE) of SmaI chromosomal DNA digests was used to compare blood culture and oral isolates of S. epidermidis and Str. oralis. The results indicated that the mouth was the source of both S. epidermidis and Str. oralis causing the first episode of bacteraemia. PFGE further demonstrated that the central venous catheter was the origin of a second strain of S. epidermidis responsible for subsequent episodes of staphylococcal bacteraemia. Both the oral mucosa and central venous lines should be considered as potential sources of organisms, including coagulase-negative staphylococci, associated with bacteraemia in immunocompromised patients.

Relationship between mucosal levels of Helicobacter pylori-specific IgA, interleukin-8 and gastric inflammation.

Mucosal IgA is important in local immune defence. Helicobacter pylori induces a specific IgA response in antral mucosa, but its immunopathology is unknown. Interleukin-8 (IL-8) has been suggested to be important in H. pylori-induced inflammation. Current information on the relationship between H. pylori-induced IgA and mucosal inflammation is limited. To investigate possible associations between mucosal-specific IgA, the toxinogenicity of H. pylori, mucosal levels of IL-8 and gastric inflammation, 52 endoscoped patients were studied. These comprised 28 patients with peptic ulcer and 24 with non-ulcer dyspepsia. Of these patients, 38 had H. pylori infection: 28 with peptic ulcer and 10 with non-ulcer dyspepsia. Antral biopsies were taken for histology, H. pylori culture and measurement of mucosal levels of IL-8 (pg/mg) and specific IgA (A450x1000) by ELISA. Mucosal H. pylori IgA was detectable in 35 out of 38 patients with H. pylori infection, with a median (interquartile) level of 220 (147, 531) units. There was no significant difference in mucosal levels of the IgA antibodies between patients infected with cytotoxin-positive or cagA-positive strains of H. pylori and those with toxin-negative or cagA-negative strains. The IgA levels in those patients with severe neutrophil infiltration were lower than in those with mild or moderate infiltration (P<0.05). There was a weak inverse correlation between antral mucosal IgA and IL-8 in infected patients (r=-0.36; P=0.04). H. pylori infection induced a significant local mucosal IgA response in most infected patients. The level of IgA antibodies does not appear to be correlated with the toxinogenicity of H. pylori. However, patients with severe active inflammation appear to have decreased levels of IgA. An inverse correlation between mucosal IL-8 and IgA may suggest that IL-8-induced inflammation compromises the mucosal IgA defence and renders the mucosa susceptible to further damage.

Where is typing going?

The basic premise in any bacterial typing scheme is that epidemiologically related isolates are derived from the clonal expansion of a single precursor. In simple terms this means that a certain characteristic is more useful than others on the basis that it is conserved within a strain but diverse with a species. Such a definition is appropriate when considering the spread of a species within a ward hospital or even a community. However, as we have developed more and more refined molecular techniques for analysis of the bacterial genome, such a definition has become stressed when considering the evolution that is occurring especially amongst drug-resistant bacteria whose genetic make-up is changing due to the selective pressure induced by drug usage in the hospital or community. Increased sophistication does not necessarily bring improved typing of bacterial strains which might only be variants of the same clonal type. Molecular epidemiology is perhaps too exacting to be practical in certain circumstances and one should be cautious in its interpretation and extrapolation. It is open to debate whether we shall see in the next century unanimity in the choice of pheno- or genotypic tests to be used for typing of bacterial strains.

Relationship between mucosal levels of interleukin 8 and toxinogenicity of Helicobacter pylori.

AIM OF STUDY: To investigate if an association exists between in-vivo mucosal levels of IL-8 and bacterial expression of cytotoxin and cagA gene of H. pylori. METHODS: Seventy-two dyspeptic patients referred for endoscopy were studied, including 36 patients with peptic ulcer (PU) and 36 with non-ulcer dyspepsia (NUD). Biopsies were taken for histology, H. pylori culture and measurement of IL-8 by ELISA. To test the ability of H. pylori to produce cytotoxin (VacA), broth culture supernatants were assayed on Vero cells and vacuolation measured. PCR was used to detect the cagA gene of H. pylori. RESULTS: H. pylori was isolated in 52 of 72 patients studied. Among the 52 strains, 25 (49%) were VacA+ve/cagA+ve; 12 (23%) were VacA-ve/cagA-ve; the remaining 15 strains (28%) were either VacA+ve/cagA-ve or VacA-ve/cagA+ve. IL-8 levels (median (interquartile) pg/mg) in patients infected with VacA+ve (1.5 (0.64, 2.84)) or cagA+ve strains (1.25 (0.72, 2.34) were significantly higher than in those with VacA-ve (0.76 (0.4, 1.0)) or cagA-ve strains (0.5 (0.4, 1.5); p<0.05). The neutrophil infiltration score was also higher in patients infected with VacA+ve or cagA+ve strains than in those infected with VacA-ve or cagA-ve strains (p<0.05). CONCLUSION: VacA+ve/cagA+ve strains were associated with an enhanced production of mucosal IL-8 in vivo and correlated with a stronger infiltration of neutrophils. Enhanced mucosal production of IL-8 and its role in neutrophil chemotaxis and activation could be important in H. pylori-induced gastroduodenal inflammation and in the development of peptic ulcer disease.

Role of certain virulence factors in a murine model of Staphylococcus aureus arthritis.

The susceptibility of male Swiss white mice (MF1) to Staphylococcus aureus-induced arthritis was investigated with wild-type strain allelic replacement mutants. Comparison was made with a known mouse arthritogenic strain. The development and severity of arthritis were dependent both on the numbers of live bacteria injected intravenously and also on the mutant used; the ID50 ranged from (5 X 10(6))-(1 x 10(8)) cfu. The results indicate that expression of the genes associated with virulence, including those for protein A and alpha-haemolysin, play a major role in the pathogenesis of staphylococcal septic arthritis. When either virulence component was carried by the S. aureus variant, a greater degree of inflammation, pannus formation and cartilage destruction was detected histologically. Loss of one or more virulence factors lowered the septic arthritis severity score based on clinical and histological parameters.

Relationship between the mucosal production of reactive oxygen radicals and density of Helicobacter pylori in patients with duodenal ulcer.

OBJECTIVE: To investigate the associations between the mucosal production of reactive oxygen radicals (RORs) in the gastric antrum and duodenum, Helicobacter pylori density and duodenal ulcer (DU). PATIENTS: Forty-seven endoscoped patients, comprising 22 with DU and 25 non-ulcer subjects, were included in the study. METHODS: Antral and duodenal biopsies were taken for histology, Helicobacter pylori culture and measurement of chemiluminescence. Biopsies were homogenized and cultured on Columbia blood agar plate. Colonies of H. pylori were counted and bacterial density expressed as colony-forming units (cfu)/mg of biopsy. Chemiluminescence was measured by luminometry and the results expressed as millivolt (mV)/min/mg of biopsy, after subtraction of background count. RESULTS: Thirty-one of 47 (66%) patients had antral H. pylori and 6/47 (12.8%) had proven duodenal colonization. Increased chemiluminescence (median (interquartile)) was found in H. pylori-infected patients compared to those without H. pylori in antral (90.0 (26.0, 249.0) vs. 7.0 (0.0, 10.0), P<0.001) and duodenal mucosa (22.0 (10.0, 100.0) vs. -2.5 (-10.0, 0.0) P<0.001). A positive correlation was found between antral H. pylori density and chemiluminescence response in both the antrum (r=0.77) and duodenum (r=0.52). DU patients showed an increased chemiluminescence compared to those non-ulcer subjects with or without H. pylori infection in antrum (163.5 (44.5, 297.8) vs. 33.0 (8.7, 168.0) (P=0.046) vs. 2.7 (0.1, 10.0), P<0.01) and duodenum (45.0 (17.5, 100.0) vs. 15.0 (-1.25, 22.5) vs. -2.5 (-10, 0.0), P<0.01). CONCLUSION: Increased production of RORs in the antrum and duodenum was found to be related to antral H. pylori density and associated with duodenal ulceration. The association between antral H. pylori and ROR release in the duodenum may be important in the pathogenesis of duodenal ulceration.

Persistence of Staphylococcus aureus as detected by polymerase chain reaction in the synovial fluid of a patient with septic arthritis.

Septic arthritis commonly occurs in the rheumatoid arthritis population. The diagnosis is frequently delayed and the associated mortality is high. In this brief report, we present a patient with rheumatoid arthritis and prosthetic knee joints who developed septic arthritis and had persisting evidence of Staphylococcus aureus DNA in synovial fluid, from his knees, which was detected by polymerase chain reaction (PCR) and a gene probe. This was detected until 10 weeks of therapy despite adequate antibiotic treatment and a sterile synovial fluid. In the future, it may be found that PCR of the synovial fluid will be a valuable investigation for the diagnosis and management of septic arthritis.

Association of antral mucosal levels of interleukin 8 and reactive oxygen radicals in patients infected with Helicobacter pylori.

1. Helicobacter pylori infection is characterized by an infiltration of neutrophils in the gastric mucosa. Neutrophil activation is an important source of reactive oxygen radicals, which cause tissue damage. Studies have shown that in Helicobacter pylori-infected patients there is increased mucosal production of interleukin 8. However, the role of interleukin 8 in the Helicobacter pylori-related inflammatory process and its relationship with reactive oxygen radicals remains to be clarified. The aims of this study were to investigate if there is any association between antral mucosal levels of interleukin 8 and reactive oxygen radicals and their relationship to gastric antral inflammation. 2. Fifty-two patients referred for endoscopy were recruited into the study. Gastric antral biopsies were taken for histology, culture and measurement of interleukin 8 and chemiluminescence (measuring reactive oxygen radicals). Interleukin 8 was measured by ELISA and the result expressed as pg/mg biopsy. Luminol-enhanced chemiluminescence was measured as mV min-1 mg-1 biopsy. Antral inflammation was assessed by a pathologist in a blinded fashion. 3. Antral mucosal levels of interleukin 8 and reactive oxygen radicals were significantly higher in Helicobacter pylori-colonized mucosa than in Helicobacter pylori-negative mucosa. After the eradication of Helicobacter pylori in patients with duodenal ulcer the median values (ranges) of interleukin 8 and reactive oxygen radicals fell from 1.21 (0.10-2.40) to 0.65 (0.00-1.60) and from 110.0 (10.0-959.0) to 14.5 (0.0-85.0) respectively. There was a positive correlation between interleukin 8 concentration and chemiluminescence response in the antral mucosa (r = 0.72). A higher interleukin 8 concentration was associated with greater neutrophil infiltration (r = 0.72) and mononuclear cell infiltration (r = 0.55); the magnitude of the chemiluminescence response was also positively associated with neutrophil (r = 0.77) and mononuclear cell infiltration (r = 0.59). 4. Interleukin 8 concentration is associated with an infiltration of neutrophils and mononuclear cells and is correlated with the production of reactive oxygen radicals in antral gastric mucosa infected with Helicobacter pylori. These findings suggest that interleukin 8 may be important in attracting and activating phagocytes to release reactive oxygen radicals, thereby causing mucosal damage.