Recombinant human deoxyribonuclease (rhDNase) is a mucolytic agent used to relieve peripheral airway obstruction in patients with cystic fibrosis. We report dramatic sustained improvement following the intratracheal administration of rhDNase to a 3-yr-old boy with acute life-threatening asthma in whom 48 h of aggressive therapy had failed.

The prevalence of Csh-like fibrillar surface proteins among oral streptococci was investigated by ELISA and by immunoelectron microscopy using antiserum raised to recombinant fragments of CshA of Streptococcus gordonii DL1. The majority of S. gordonii, Streptococcus sanguis and Streptococcus oralis strains tested elaborated short (ca. 50-80 nm long) surface fibrils and reacted with antiserum to the amino acid repeat region of CshA, demonstrating the widespread nature of Csh-like proteins among these species. In contrast, reactivity with antiserum raised to the adhesion-mediating non-repetitive region of CshA was more restricted. On the basis of the ELISA results, several isolates were selected for immunogold analysis using CshA antisera. Immunogold-negative staining showed a surface distribution of 10 nm gold particles consistent with antibody binding to short fibrils. Long fibrils (>150 nm long), where present, were not significantly labelled with gold. The results suggest that some of the short peritrichous fibrils on many mitis group streptococci comprise Csh-like fibrillar protein. Further, the data are consistent with our hypothesis that the antigenically conserved amino acid repeat region of Csh-like proteins forms a scaffold for cell-distal presentation of the amino-terminal non-repetitive region that, at least in S. gordonii DL1, functions as an adhesin.

When tested in three experimental staphylococcal infections—acute peritonitis in mice, mouse leg edema produced by a localized infection, and dermal rabbit ear infections—lysostaphin demonstrated in vivo chemotherapeutic activity. Doses of less than 0.007 mg/kg (intraperitoneally) and 0.5 mg/kg (subcutaneously) of lysostaphin prevented death in 50% of the mice with acute staphylococcal peritonitis. A single intramuscular dose (0.15 mg/mouse) of lysostaphin suppressed the swelling produced by the injection of staphylococci into mouse legs to 50% of that produced in untreated animals. Lysostaphin (0.05% by weight) incorporated into gels and applied topically eradicated staphylococci from experimental skin lesions on the ears of rabbits. Lysostaphin was absorbed and transported by the body fluids from the point of injection to the site of the infection producing a desirable antistaphylococcal effect.

By use of a renal staphylococcal infection model in mice, single intravenous doses of lysostaphin ranging from 1.56 to 50 mg/kg were effective in: (i) controlling the staphylococcal population of kidneys, (ii) reducing the mortality rate, and (iii) clearing high numbers of kidneys of infection. Semisynthetic penicillins and other antistaphylococcal antibiotics given in the same manner did not have significant activity. Only by the administration of a long-acting, depot form of penicillin (Bicillin) could results comparable to those seen with lysostaphin be obtained. The results of this study suggest that lysostaphin may be useful in staphylococcal septicemias in preventing the establishment of new foci of infection.

BRUCE CROPP. Comparative in vitro activities of lysostaphin and other antistaphylococcal antibiotics on clinical isolates of Staphylococcus aureus. Appl. Microbiol. 13:212-215. 1965.-The in vitro activity of lysostaphin against clinical isolates of Staphylococcus aureus was determined by conventional tube-dilution methods. For comparison, minimal inhibitory concentration (MIC) values were also determined for penicillin G, ampicillin, methicillin, ristocetin, vancomycin, and erythromycin. Phage type and penicillinase and coagulase production were determined for each isolate. The MIC values for lysostaphin ranged from <0.047 to 12.5 ,g/ml; 96% of the penicillinasepositive strains were inhibited by 1.56 ,Ag/ml of lysostaphin, whereas 3.12 ,ug/ml of vancomycin and methicillin were required to attain the same degree of inhibition.