Haemophilus influenzae Infection of Human Respiratory Mucosa in Low Concentrations of Antibiotics

A prospective randomized study was performed in order to compare the efficacy of oral levofloxacin, a new S-isomer of ofloxacin, with intravenous ceftazidime in the empirical treatment of acute exacerbations of bronchiectasis.Consecutive patients with acute exacerbation of bronchiectasis were recruited at a tertiary referral centre and were randomized to receive 10 days' treatment with either oral levofloxacin (300 mg b.i.d.) or ceftazidime (1 g i.v. t.i.d.). Body temperature, cough score, dyspnoea score, sputum purulence and volume and white blood cell and neutrophil count were assessed on day 1 and day 10.Thirty-five patients (mean age 61 yrs, 15 males) completed the study; 17 of these were in the levofloxacin group. There was no significant difference in the distribution of sputum pathogens or clinical parameters between the two groups at entry to and completion of the study. Both groups of patients showed significant improvement in 24-h sputum volume, sputum purulence score, cough score and dyspnoea score (p<0.001) but there was no significant difference between these two groups at entry to or on completion of the study (p>0.05).The results of this study suggest that oral administration of levofloxacin is as effective as parenteral ceftazidime in the empirical treatment of exacerbations in bronchiectasis.

Section: Discussionmentioning

confidence: 99%

A comparative study on the efficacy of levofloxacin and ceftazidime in acute exacerbation of bronchiectasis

Tsang¹,

Chan²,

Ho³

et al. 1999

“…For TEM, the specimens were coded so that the observer was unaware of their treatment. Each cell was scored for four parameters [20]: 1) loss of cilia from ciliated cells, 0 (fully ciliated), 1, 2, 3 (only one or two visible cilia); 2) extrusion of the cells from the epithelial surface, 0 (absent), 1, 2, 3 ,4 (cell completely extruded from epithelial surface but still in contact with other epithelial cells); 3) cytoplasmic blebbing, 0 (absent), 1 (minor) or 2 (major); and 4) mitochondrial damage, manifested as swelling and disruption of mitochondrial cristae, 0 (absent) or 1 (present). As the relative significance of the TEM parameters was unclear, the score attributed to each was adjusted, so that a final maximum possible damage score of 100 was obtained for each of the four parameters.…”

Section: Tem Assessmentmentioning

confidence: 99%

“…The percentages of cells with extrusion from the epithelial surface was calculated by the difference between 100 and the percentage of cells with no extrusion. Likewise, the percentages of cells with loss of cilia, cytoplasmic blebbing and mitochondrial damage were calculated [20].…”

Section: Tem Assessmentmentioning

confidence: 99%

Interaction of Pseudomonas aeruginosa with human respiratory mucosa in vitro

Tsang

Rutman²,

Tanaka³

et al. 1994

100

I In nt te er ra ac ct ti io on n o of f P Ps se eu ud do om mo on na as s a ae er ru ug gi in no os sa a w wi it th h h hu um ma an n r re es sp pi ir ra at to or ry y m mu uc co os sa a i in n v vi it tr ro o Transmission electron microscopy (TEM) showed that uninfected organ cultures had normal ultrastructure. TEM of infected organ cultures at 8 h showed significant epithelial damage: 43.9±10% of cells extruding from the epithelial surface, 17.7±3% of cells with loss of cilia, 32.9±10.2% of cells with mitochondrial damage, and 11.6±3% of cells with cytoplasmic blebbing. P. aeruginosa only infrequently adhered to normal epithelium, but adhered to areas of epithelial damage and to basement membrane. Scanning electron microscopy (SEM) of organ cultures up to 2 h found P. aeruginosa only infrequently associated with mucus. SEM at 4 h revealed P. aeruginosa predominantly associated with mucus and extruded damaged epithelial cells, but also occasionally associated with cilia, and very occasionally with unciliated cells. SEM also revealed loss of epithelial tight junctions in P. aeruginosa infected organ cultures, and P. aeruginosa were frequently seen in the gaps between epithelial cells. An extracellular matrix, possibly of bacterial origin, was seen bridging the space between bacteria and cell surface.We conclude that P. aeruginosa infection of this organ culture caused tissue damage and that P. aeruginosa preferentially adhered to mucus, damaged epithelium and basement membrane.

“…P. aeruginosa exotoxins, such as pyocyanin, 1-hydroxylphenazine and rhamnolipid, can also expose the basement membrane to P. aeruginosa bacilli through slowing of ciliary beating, separation of epithelial tight junctions, and sloughing of damaged respiratory mucosa [7,9]. As many intraluminal bacteria are adherent to respiratory mucus, many workers believe that this could be a reservoir for persistent airway pathogens, such as P. aeruginosa and Haemophilus influenzae [7,14]. However, respiratory mucus is eventually expectorated and cannot subsequently retain these pathogens in the airways.…”

Section: Discussionmentioning

confidence: 99%

Pseudomonas aeruginosaadherence to human basement membrane collagenin vitro

Tsang¹,

Shum²,

Chan³

et al. 2003

The mechanisms for Pseudomonas aeruginosa colonisation in the airways of patients with bronchiectasis and cystic fibrosis are poorly understood. P. aeruginosa could evade mucociliary clearance by adhering to the basement membrane at areas denuded of intact respiratory epithelium.The authors have developed an in vitro model to study P. aeruginosa adherence to human basement membrane type-IV collagen by using scanning electron microscopy. P. aeruginosa adherence density was determined as the number of P. aeruginosa per 20 microscope fields (2,0006) to log inocular size after incubation at 37uC for 45 min.The presence of phytohaemagglutinin (PHA)-E, which binds specifically to D-galactose-b1-4-D-N-acetylglucosamine, significantly reduced P. aeruginosa adherence density compared with control. The presence of heparin and calcium also significantly reduced P. aeruginosa adherence density. P. aeruginosa adherence was not affected by the presence of proline, trans-hydroxyproline, glycine, galactose, N-acetylneuraminic acid, N-acetylglucosamine or Arachis hypogea.Pseudomonas aeruginosa adherence probably acts via recognition of the D-galactoseb1-4-D-N-acetylglucosamine sequence on type-IV collagen and this process could be inhibited by heparin and calcium. As persistent Pseudomonas aeruginosa colonisation is detrimental to patients with cystic fibrosis and bronchiectasis and there is currently no effective treatment for its eradication, these results could lead to novel therapy for persistent Pseudomonas aeruginosa infection. Eur Respir J 2003; 21: 932-938.