Biomedical subjects

C G Gemmell

Publications and source records attributed to C G Gemmell.

At least 19 recordsLinked to original sources

PubMed2003

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.

Anti-Bacterial Agents↗

PubMed2001

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.

Anti-Bacterial Agents↗

PubMed2001

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.

Acetamides↗

PubMed2001

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.

Anti-Bacterial Agents↗

PubMed2001

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.

Animals↗

PubMed2000

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.

Adolescent↗

PubMed2000

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.

Antibodies, Monoclonal↗

PubMed1999

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.

Bacterial Typing Techniques↗

PubMed1999

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.

Adult↗

PubMed1997

Attenuated neutrophil respiratory burst following acute hypoglycaemia in diabetic patients and normal subjects.

The effects of insulin-induced hypoglycaemia on the neutrophil respiratory burst were investigated in six patients with type 1 diabetes and six non-diabetic control subjects. Plasma glucose reached similar nadirs in control subjects (0.9 +/- 0.1 mmol 1(-1); mean +/- SEM) and diabetic patients (1.2 +/- 0.2 mmol 1(-1)) (NS). The resting neutrophil respiratory burst was similar in control subjects (1.26 +/- 0.15 mV) and diabetic patients (1.03 +/- 0.18 mV) (NS). The neutrophil respiratory burst fell following hypoglycaemia in control subjects and diabetic patients to 0.38 +/- 0.05 mV (P < 0.001) and 0.54 +/- 0.09 mV (P < 0.05), respectively. This fall was significantly greater in control subjects (ANOVA; P < 0.001). Resting neutrophil counts were not significantly different in control subjects (3.2 +/- 0.3 x 10(9) 1(-1)) and diabetic patients (6.1 +/- 1.5 x 10(9) 1(-1)). Following hypoglycaemia, neutrophil numbers increased in control subjects and diabetic patients to 11.5 +/- 1.4 x 10(9) 1(-1) (P < 0.01) and 9.7 +/- 1.7 x 10(9) 1(-1) (P < 0.05), respectively. This increase was significantly greater in control subjects (ANOVA; P < 0.001). These results suggest that the neutrophil respiratory burst is suppressed in response to hypoglycaemia and that this phenomenon is more pronounced in non-diabetic subjects.

Acute Disease↗

PubMed1997

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.

Duodenal Ulcer↗

PubMed1997

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.

Aged↗

PubMed1997

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.

Biopsy↗

PubMed1997

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.

Animals↗

PubMed1996

Studies into the role of the SEF14 fimbrial antigen in the pathogenesis of Salmonella enteritidis.

To investigate the role of the SEF14 fimbrial antigen in pathogenesis, a single defined sefA (SEF14-) inactivated mutant of Salmonella enteritidis strain LA5 was constructed and tested in a number of biological assay systems. There was no significant difference between the wild-type strain and the isogenic SEF14- mutant in their abilities to adhere to and invade HEp-2 epithelial cells or their survival in mouse peritoneal macrophages, whereas the SEF14- mutant was ingested more rapidly by isolated human PMN. Both the strains colonized the intestine, invaded and spread systemically in 1 day-old chicks, laying hens and BALB/c mice equally well. A significantly greater number of chicks excreted the wild-type SEF14+ strain during the first week following infection as compared to those infected with the SEF14- mutant. However, similar numbers of chicks excreted the two strains between 2 and 7 weeks after infection. These results indicate that possession of SEF14 fimbriae alone do not appear to play a significant role in the pathogenesis of S. enteritidis although its contribution to virulence may be dependent on the host species infected.

Animals↗

PubMed1996

Effect of omeprazole therapy on the survival of Helicobacter pylori, urease activity, and antral gastric histology in patients with duodenal ulcer.

BACKGROUND: Helicobacter pylori is associated with chronic active gastritis and peptic ulceration (PU). Omeprazole is a proton pump inhibitor that is effective in healing PU and reducing gastritis. Previously it has been found that omeprazole has some bacteriostatic activity against H. pylori both in vitro and in vivo and in inhibiting urease activity in vitro. Our aim was to evaluate the effect of omeprazole on H. pylori colonization of the gastric mucosa, urease activity in vivo, and the presence of associated gastritis in patients with duodenal ulcer (DU). MATERIALS AND METHODS: We studied 12 patients (7 men and 5 women, ages 22-68 yr) with Du larger than 5 mm in diameter with a positive CLOtest (Delta West Ltd., Australia). Omeprazole, 20 mg bid, was given for 8 weeks to each patient, patients were endoscoped at the end of this period to check for healing of DU, and repeat biopsies were obtained from the gastric antrum for histological analysis, CLOtest, and culture. RESULTS: DU healed completely in all patients. Likewise in all patients there was significant reduction in the urease activity, from 22.1 +/- 4.17 to 1.58 +/- 0.92 units/ml (p < .001; 95% confidence interval of the difference between means, 32.7-14.1), and reduced H. pylori density, from 1,403.46 +/- 128.23 to 422.5 +/- 172.39 colony-forming units (CFU) per milligram of tissue biopsy (p < .001; 95% confidence interval of the difference between means, 1,486.1-590.5). The numbers of H. pylori were reduced on the gastric mucosa after omeprazole therapy and disappeared in six patients, a result that correlated with a negative CLOtest reading after 24 hours. CONCLUSION: Omeprazole, 20 mg bid, is capable of reducing H. pylori numbers and urease activity in vivo. There was no significant reduction in the severity of antral gastritis in DU patients studied.

Adult↗

PubMed1996

Association of cytotoxin production and neutrophil activation by strains of Helicobacter pylori isolated from patients with peptic ulceration and chronic gastritis.

BACKGROUND: Helicobacter pylori is associated with neutrophil infiltration within the gastroduodenal mucosa. Neutrophil activation provides a major source of oxygen free radicals, which have been implicated in the pathogenesis of peptic ulceration. AIM: To investigate if cytotoxin producing strains of H pylori are associated with the generation of oxidative burst in polymorphonuclear neutrophils (PMNs). PATIENTS: 76 patients undergoing endoscopy of whom 45 had peptic ulcer and 31 chronic gastritis only were studied. METHODS: Strains of H pylori were cultured in Brucella broth. After 48 hours, bacteria were harvested by centrifugation and a bacterial suspension prepared as a stimulus for PMN oxidative burst using chemiluminescence. PMNs were prepared from health blood donors. To test the ability of strains to produce cytotoxin, culture supernatants of each were concentrated by polyethylene glycol and tested on cultured Vero cells for intracellular vacuolation. RESULTS: 30 of 45 (66.7%) peptic ulcer patients induced cell vacuolation versus nine of 31 (29%) strains from patients with chronic gastritis only (p < 0.01). Cytotoxin positive strains of H pylori regardless of the presence or absence of peptic ulcer displayed an increased induction of respiratory burst in PMNs compared with toxin negative strains from patients with chronic gastritis only (p < 0.05). Among the toxin negative strains, those from patients with peptic ulcer did not show a significant increase of the oxidative burst than those from patients without peptic ulcer (NS). CONCLUSION: Toxinogenicity of strains of H pylori seems to be correlated with neutrophil respiratory burst and peptic ulceration. The ability of some strains of H pylori to produce cytotoxin and to induce the oxidative burst in neutrophils may be important in the pathogenesis of peptic ulcer disease.

Adult↗

PubMed1996

Antibiotics and the host-parasite relationship (a short review).

The last twenty years have witnessed an increasing interest in the concomitant action that an antibiotic may have on cells other than its primary target, the bacterial or fungal cell. It is now recognized that some may exert direct immunomodulatory effects (positive and negative) on cells of the host's immune response (polymorphonuclear neutrophils, macrophages and T lymphocytes). Others may concentrate within phagocytic cells, remain bioactive therein and be transported involuntarily to sites of infection. In addition, there is evidence that a number of antibiotics, primarily those which act by inhibition of bacterial protein synthesis, interfere with the expression of structural virulence factors rendering the producer bacteria more or less susceptible to phagocytic ingestion and killing. It remains likely that some of all of these activities may occur in vivo during therapy.

Anti-Bacterial Agents↗