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Keywords:

  • Pseudomonas aeruginosa;
  • opsonization;
  • immunotheraphy;
  • IV gamma globulin;
  • lipopolysaccharide antibodies

Abstract

We studied the effect of an intravenously administered gamma globulin [Ps-ivlG] enriched fivefold over conventional ivlG for Pseudomonas aeruginosa lipopolysaccharide [PA LPS] antibodies on ten patients with cystic fibrosis [CF] aged 19–32 years during hospitalization for pulmonary deterioration. All were colonized with ≥1 PA phenotype resistant to all antibiotics at the time of admission and they received 500 mg/kg Ps-ivlG intravenously as a single dose in addition to conventional treatment, including antibiotics and chest physiotherapy. No adverse effects occurred. Circulating immune complexes and complement levels remained unchanged from baseline. Serum levels of anti-PA LPS lgG, as measured by ELISA for eight PA LPS immunotypes, increased to 244 ± 65% (mean ± SE) of baseline levels 1 hour post-infusion (P < 0.01), remained significantly elevated during a mean hospital stay of 17 days, and returned to near baseline by follow-up 4 weeks after hospital discharge. Plasma half-life and clearance values were similar to those of other subjects receiving conventional ivlG. Sputum PA density declined from 3.0 to 1.2 × 108 cfu/mL 1 week post-infusion (P ≌ 0.05), and returned to baseline at follow-up. Serum anti-PA opsonic activity increased after infusion (P < 0.01), but returned to baseline by 72 hours. Clinical scores improved from admission to discharge (P < 0.005) without decline at follow-up. Forced vital capacity [FVC] and forced expiratory volume in one second [FEV1] increased from admission to discharge (P < 0.01 and P < 0.05, respectively) without decline at follow-up. Using autologous historical control data, standard hospital therapy without Ps-ivlG resulted in no improvement in FVC or FEV1, and a subsequent decline in these parameters (P < 0.05 for each) during a similar follow-up period. This occurred despite the fact that half the patients did not have antibiotic-resistant PA on the control admission. We conclude that Ps-ivlG is a safe adjunctive therapy for pulmonary exacerbations in moderately ill cystic fibrosis patients colonized with resistant PA, and may be associated with both greater and more prolonged improvement in pulmonary function than standard therapy alone. Pediatr Pulmonol 1990; 9:7–18.