The opportunistic gram-negative bacterium Pseudomonas aeruginosa is implicated in many chronic infections and is readily isolated from chronic wounds, medical devices, and the lungs of cystic fibrosis patients. P. aeruginosa is believed to persist in the host organism due to its capacity to form biofilms, which protect the aggregated, biopolymer-embedded bacteria from the detrimental actions of antibiotic treatments and host immunity. A key component in the protection against innate immunity is rhamnolipid, which is a quorum sensing (QS)-regulated virulence factor. QS is a cell-to-cell signaling mechanism used to coordinate expression of virulence and protection of aggregated biofilm cells. Rhamnolipids are known for their ability to cause hemolysis and have been shown to cause lysis of several cellular components of the human immune system, for example, macrophages and polymorphonuclear leukocytes (PMNs). In this chapter, the interplay between P. aeruginosa and the PMNs in chronic infections is discussed with focus on the role of rhamnolipids and extracellular DNA.

Pseudomonas aeruginosa biofilms: mechanisms of immune evasion.

(1972). Pseudomonas Aeruginosa Infections. CRC Critical Reviews in Clinical Laboratory Sciences: Vol. 3, No. 3, pp. 291-347.

Pseudomonas Aeruginosa Infections

Blood and urine concentrations of a new aminoglycoside, tobramycin, were compared with those of gentamicin after intravenous and intramuscular administration in healthy adult volunteers. Serum concentrations for the two antibiotics were the same after an intravenous infusion of 100 mg for the first haur (about 4.75 p.g per milliliter), during the steady state attained by infusing 30 mg per hour for the next 2 haurs (about 3.85 p.g per milliliter), and during the elimination phase after the antibiotics were stopped. After a single intramuscular injection of 100 mg, the blood level curves were equal and the peak concentrations at 20 to 45 minutes were the same as those obtained after intravenous infusion of the same dose for 1 hour. Between 80% and 90% of each of the two antibiotics was recovered in the urine within 24 hours. Plasma clearance was not significantly higher than renal clearance, and glomerular filtration seemed to be the main pathway of elimination. The two aminoglycosides had an apparent volume of distribution of about 30% total body weight. Each had a half-life of 2 hours.

Comparative pharmacokinetics of tobramycin and gentamicin.

The in vitro susceptibility to BB-K8, butirosin, gentamicin, sisomicin, and tobramycin of seven groups of clinically significant gram-negative bacilli and Staphylococcus aureus was assessed by using the International Collaborative Study-World Health Organization criteria. The activity of gentamicin, sisomicin, and tobramycin generally paralleled each other. Sisomicin was the most potent compound by weight and usually demonstrated the most rapid rate of killing. BB-K8 and butirosin were less potent, but higher serum levels may be achieved with these agents. BB-K8 generally showed the greatest ratio between achieveable mean peak serum levels and concentrations needed to inhibit [Formula: see text] of each group of organisms tested. Additionally, BB-K8 was active against six of seven highly gentamicin-resistant strains. All of these antibiotics showed diminished activity at pH 6.4 but only gentamicin and sisomicin showed occasionally enhanced activity at pH 8.4.

Activity of Five Aminoglycoside Antibiotics In Vitro Against Gram-Negative Bacilli and Staphylococcus aureus

Gentamicin, sisomicin, tobramycin, and kanamycin were compared in parallel tests in vitro and in vivo against a variety of bacterial strains and species A number of differences were seen in vitro, in particular: (i) the lower activity of kanamycin, (ii) the greater activity of tobramycin against Pseudomonas, (iii) the greater activity of gentamicin and sisomicin against Serratia, and (iv) the generally similar results with tobramycin, gentamicin, and sisomicin against species other than Pseudomonas and Serratia, with the ranking in order of decreasing activity being sisomicin, gentamicin, and tobramycin Analysis of disc test results suggested that the gentamicin disc is not adequate for testing the susceptibility of all bacteria to sisomicin or tobramycin In vivo tests did not confirm all specifics of in vitro tests; results of in vivo tests indicated that sisomicin may be the most active It is suggested that the place of each of the antibiotics in human therapy can best be evaluated by more rigorous in vivo tests and clinical studies rather than extensive in vitro comparisons

Comparative Activity of Sisomicin, Gentamicin, Kanamycin, and Tobramycin

Tobramycin (factor 6 of the nebramycin complex) is a new aminoglycoside antibiotic isolated from Streptomyces tenebrarius which is active against S. aureus, Enterobacteriaceae, and Pseudomonas aeruginosa. Susceptibility to tobramycin of 96 strains of P. aeruginosa, including 45 recent isolates from blood, was studied by using agar and broth dilution methods. The minimum inhibitory concentration (MIC) for 83 of 96 strains was 3.12 μg/ml or lower in Mueller Hinton agar; MIC values were two to eight times lower in Mueller Hinton broth tests. Agar dilution MIC values were generally lower than those obtained in parallel tests with gentamicin. Killing curves obtained from serial sampling of broth cultures showed a 100- to 10,000-fold decline in viability of log-phase organisms within 30 min of exposure to the drug. Two-dimensional agar dilution tests with carbenicillin and tobramycin with 79 strains showed additive or synergistic effects; no antagonism was documented. Seventy-eight of 79 strains were inhibited by a combination of 50 μg of carbenicillin per ml and 1.56 μg of tobramycin per ml, blood levels which seem attainable in man. Tobramycin appears to be a potent, rapidly bactericidal antibiotic against P. aeruginosa and merits clinical evaluation.

D. Armstrong

Papers

Tobramycin (nebramycin factor 6): in vitro activity against Pseudomonas aeruginosa.