Nedocromil in the outpatient management of asthma.

OBJECTIVE: To more closely approximate the use of a nonsteroidal inhaled anti-inflammatory medication for asthma, nedocromil sodium, under actual ambulatory practice conditions. DESIGN: Large, open-label trial. PATIENTS: One thousand two hundred one patients from 286 primary care and specialty centers. INTERVENTION: Four weeks of treatment with nedocromil sodium (4 mg delivered from the valve and 3.5 mg delivered from the mouthpiece of a metered inhalor [2 puffs, four times daily]). MAIN OUTCOME MEASURES: Asthma symptom scores, peak expiratory flow rate, a lifestyle assessment measures questionnaire, and mean number of days missed per month from work or school. RESULTS: Statistically significant improvements were seen after 1 and 4 weeks of treatment for cough, daytime and nighttime asthma, morning tightness, peak expiratory flow rate, and all four measured lifestyle assessment factors (P < .001). An additional clinically relevant outcome measure, mean number of days missed per month from work or school, was reduced by 75% (P < .001). No serious adverse reactions were reported. CONCLUSION: This study reproduces the high level of efficacy and safety of nedocromil that was previously reported in placebo-controlled clinical studies.

Invasive disease due to Streptococcus pneumoniae in an area with a high rate of relative penicillin resistance.

During 1984 we conducted a population-based survey of culture-confirmed invasive disease due to Streptococcus pneumoniae among persons who lived in the Oklahoma City, Oklahoma, metropolitan area (population, 846,000) through the 20 clinical laboratories in the area. There were 139 residents identified with invasive pneumococcal disease (11 with meningitis and 128 with other bacteremic infections), for an infection rate of 16.4 per 100,000 population (meningitis, 1.3 cases per 100,000; other bacteremias, 15.1 cases per 100,000). Cases peaked in January-May and December (75% of cases). Rates were highest among infants less than 12 months old (97 cases per 100,000) and persons greater than or equal to 80 years old (87 cases per 100,000). Seventeen (12.2%) of the pneumococcal isolates were relatively penicillin resistant. These isolates were most prevalent among elderly persons greater than or equal to 70 years old (six [17.6%] of 34) and young children 0-4 years old (7 [15.9%] of 44) compared with persons 5-69 years old (four [6.6%] of 61).

Soft-tissue infections caused by Mycobacterium fortuitum complex following penetrating injury.

Soft-tissue infections caused by rapidly growing mycobacteria may follow penetrating trauma. We present four immunologically normal patients in whom soft-tissue infections with Mycobacterium fortuitum developed after they stepped on nails. Their presentations were clinically indistinguishable from puncture wound infections caused by Pseudomonas aeruginosa and Staphylococcus aureus. The acid-fast organisms grew on standard bacteriologic media within three to five days. Speciation and antimicrobial susceptibility testing was performed. The primary mode of therapy was surgical; adjunctive antimicrobial therapy is recommended only for extensive or chronic infections and in immunocompromised hosts. All four of our patients had good outcomes after therapy.

The extended microbiology of group A streptococcal pharyngitis. Observations during a double-blind controlled study of cephalexin twice versus four-times daily.

In a double-blind controlled study we compared the effectiveness of cephalexin b.i.d. versus q.i.d. in the treatment of group A streptococcal pharyngitis in 65 children. Clinical improvement was noted in 64 patients (98%) and bacteriologic cure in 60 (92%). Despite good compliance, three bacteriologic failures were noted in the q.i.d., and two in the b.i.d. treatment groups. Two of these five were carriers. Significant antibody responses were observed in 61% of the patients by at least one of three tests (ASO, anti-DNase B, Streptozyme). We also investigated the extended microbiology of streptococcal pharyngitis by looking for the presence of viruses, chlamydia and beta-lactamase producing organisms in the pharynx. Respiratory viruses were isolated concomitantly with Streptococcus pyogenes in six patients. Beta-lactamase producing bacteria were present in the pharynx of 98% of the patients at the initiation of treatment and comprised 1-98% of the total bacterial flora. The beta-lactamase producing flora did not significantly change with cephalexin therapy.

In vitro activity of antibiotics commonly used in the treatment of otitis media against Streptococcus pneumoniae isolates with different susceptibilities to penicillin.

Susceptibilities of 82 clinical isolates of Streptococcus pneumoniae, including 25 from the middle-ear fluid, were evaluated against antibiotics commonly used in the treatment of acute otitis media. Potentially significant resistance occurred in 6% of the isolates to erythromycin and an erythromycin-sulfisoxazole combination. The combination of trimethoprim and sulfamethoxazole was synergistic for 95% of the isolates. Only 2.5% of all of the isolates were resistant to both erythromycin-sulfisoxazole and trimethoprim-sulfamethoxazole. The presently used drug regimens should be effective against the majority of S. pneumoniae isolates in otitis media.

Activities of various beta-lactams and aminoglycosides, alone and in combination, against isolates of Pseudomonas aeruginosa from patients with cystic fibrosis.

The inhibitory and bactericidal activities of carbenicillin, ticarcillin, moxalactam, cefoperazone, azlocillin, piperacillin, ceftazidime, and three aminoglycosides, alone and in various combinations, were determined against 60 isolates of Pseudomonas aeruginosa from the sputum of patients with cystic fibrosis. Ceftazidime was the most active beta-lactam, with minimum inhibitory and bactericidal concentrations for 90% of isolates of 4 micrograms/ml. Moxalactam was the least active of the new beta-lactams, with activity equivalent to that of carbenicillin; each had a minimum inhibitory concentration for 90% of isolates of 64 micrograms/ml and a minimum bactericidal concentration for 90% of isolates of 128 microgram/ml. All combinations of an aminoglycoside plus a beta-lactam showed favorable inhibitory effects. Combinations of beta-lactams showed mostly addition or indifference. Although little antagonism was seen with combinations of beta-lactams or with aminoglycoside-beta-lactam combinations, no consistent advantage of beta-lactam combinations was demonstrated in vitro. These results suggest several single drugs and combinations that merit clinical evaluation in cystic fibrosis patients with Pseudomonas pulmonary infections.

In vitro activity of moxalactam and cefoperazone against Streptococcus pneumoniae with differing susceptibilities to penicillin.

In vitro studies were performed to examine the potential usefulness of two new drugs, moxalactam and cefoperazone, for the treatment of infections caused by Streptococcus pneumoniae. 34 isolates of S. pneumoniae with differing susceptibilities to penicillin were examined by disk diffusion, agar and microbroth dilution methods. Isolates highly resistant to penicillin (MIC greater then 1 microgram/ml) were also resistant to moxalactam (MIC = 128 micrograms/ml) but were sensitive to cefoperazone (MIC = 2--4 micrograms/ml). All isolates relatively resistant to penicillin (MIC 0.25--0.5 micrograms/ml) were sensitive to cefoperazone (MIC 0.25--1 microgram/ml) and had moxalactam MICs of 4--16 micrograms/ml for 10/12 isolates. The disk diffusion test was unreliable for detecting strain relatively resistant to moxalactam. These studies showed that cefoperazone is more active than moxalactam in vitro against S. pneumoniae regardless of the penicillin susceptibility of these bacteria.

Antimicrobial susceptibility testing of Streptococcus pneumoniae by micro-broth dilution.

Thirty-three clinical isolates of Streptococcus pneumoniae were tested for susceptibility to penicillin and ampicillin by a standard agar dilution method. Results were compared to those obtained using a micro-broth dilution technique in which Mueller-Hinton broth was supplemented with 5% difibrinated whole sheep blood. Among the 33 strains, 2 were resistant (minimal inhibitory concentration, 8 micrograms/ml), 10 were relatively resistant (minimal inhibitory concentration, 0.12 to 0.5 micrograms/ml), and 20 were susceptible (minimal inhibitory concentration, less than or equal to 0.06 micrograms/ml) to penicillin by both methods. Only one stain showed a two-dilutional-step difference by micro-broth and agar dilution testing resulting in categorization as relatively resistant by the former method but susceptible by the latter. A 1-microgram oxacillin disk correctly identified 11 of the 12 resistant strains. The micro-broth dilution technique is a reliable, simple method for penicillin or ampicillin susceptibility testing of pneumococci and economically feasibile to perform manually or with a semiautomated system.

Vasculitis in cytomegalovirus infection.

A 7-year-old girl had fever, arthralgia, and a mild cutaneous vaculitis with papules, nodules, and livedo. A biopsy specimen of a papule showed lymphocytic small-vessel vasculitis, with some atypical lymphocytic nuclei. Splenomegaly developed, and results of subsequent studies supported a diagnosis of cytomegalovirus (CMV) infection, with atypical peripheral blood lymphocytes and a characteristic pattern of complement-fixing antibodies to CMV antigen. The CMV mononucleosis syndrome is rarely reported in children, and the cutaneous manifestations are usually rubelliform. Distinctive cutaneous pathologic characteristics have been described previously only in neonates ("blueberry muffin" syndrome) and in immunosuppressed patients (viral inclusion bodies in endothelial cells).

Relative resistance to penicillin in the pneumococcus. A prevalence and case-control study.

Isolates of Streptococcus pneumoniae from 103 patients were submitted for serotyping and determination of the minimum inhibitory concentration (MIC) for penicillin. Isolates from 16 patients were relatively resistant to penicillin (MIC, 0.1 to 0.5 micrograms/mL). In a study to determine if the patients with relatively resistant pneumococci (RRP) differed from patients with normally susceptible pneumococci, 18 patients with RRP showed no significant difference from their matched controls in antibiotic use during the two months prior to isolation of the pneumococcus. Other variables that showed no significant difference between the two groups were (1) antibiotic use in household contacts in the previous six months, (2) presence of chronic infection in the case or control patients, and (3) recurrence of pneumococcal infection following therapy. The high rate of relative resistance to penicillin is heretofore unknown in a general, unconfined population in this country. The case-control study suggests that no strong relationship exists between isolating RRP and prior penicillin administration. More extensive surveys in the United States are needed.

Multiple changes of penicillin-binding proteins in penicillin-resistant clinical isolates of Streptococcus pneumoniae.

Penicillin-binding properties and characteristics of penicillin-binding proteins (PBPs) were investigated in several clinical isolates of Streptococcus pneumoniae differing in their susceptibilities to penicillin (minimal inhibitory concentration [MIC], 0.03 to 0.5 microgram/ml) and compared with the penicillin-susceptible strain R36A (MIC, 0.07 microgram/ml). Several changes accompanied the development of resistance: the relative affinity to penicillin of whole cells, isolated membranes, and two major PBPs after in vivo or in vitro labeling decreased (with increasing resistance). Furthermore, one additional PBP (2') appeared in four of five relatively resistant strains with an MIC of 0.25 microgram/ml and higher. PBP 3 maintained the same high affinity toward penicillin in all strains under all labeling conditions.

Septicemia in children with cancer.

Because of the persistently high mortality from sepsis in cancer patients, a retrospective study was designed to identify the causative organisms and to determine the factors affecting the outcome of sepsis. A total of 84 episodes of septicemia in 61 children with cancer were studied. The more frequently isolated organisms were: Staphylococcus aureus (21.4%); Escherichia coli (18%); Klebsiella (7.1%); Pseudomonas (6%); and Bacteroides fragilis (6%). Other isolates included Proteus, Serratia, Acinetobacter, hemolytic Streptococcus, and Bacillus cereus. In 10.7% of septic episodes, mixed bacterial infections were documented. Twenty-four (28.6%) resulted in death; in 13 (54%) death occurred within 24 hours after admission. The fatality rate was high in cases associated with absolute polymorphonuclear leukocyte counts of less than 100/cu mm, in neoplastic relapse, and when infection with gram-negative, anaerobic and mixed bacterial flora occurred.

Recurrent group B streptococcal infections: Report of three cases.

The group B streptococcus has become a leading cause of neonatal infection. Despite the increasing incidence of this infection, recurrence in the same patient is extremely uncommon. This report describes three infants with proved recurrent group B streptococcal disease. All patients were treated with benzylpenicillin for at least 10 days, but, after a symptom-free interval, each developed symptoms again. Whether the illness in these patients represents a relapse or a true reinfection is difficult to determine. Various possibilities are discussed. The development of a recurrent infection indicates that presently recommended therapy may be inadequate in certain instances. Comments about epidemiology, clinical picture, antibiotic sensitivity studies, and immunity are made along with speculations about possible approaches to treatment and prevention of this infection.

Serotypes and antibiotic susceptibilities of Pseudomonas aeruginosa isolates from single sputa of cystic fibrosis patients.

A phenotypic characterization of Pseudomonas aeruginosa from single sputum samples of 21 typical cystic fibrosis patients indicated a high frequency of heterogeneity among isolates on the basis of differences in antibiotic resistance, colony morphology, pigmentation, and serotype. Two or more isolates with different but stable susceptibilities to carbenicillin, gentamycin, streptomycin, tetracycline, chloramphenicol, and sulfamethoxazole plus trimethoprim were detected in 38% of the sputa. Differences generally were independent of the mucoid state of the strain. O-antigen group determination with the Difco typing set showed that two or more serologically distinct strains were present in 10/21 sputum specimens. Nonmucoid derivatives of mucoid isolates almost always retained both the antibiotic susceptibilities and serotype of their parent strain. These data suggest that cystic fibrosis patients may be cocolonized/coinfected by different strains of P. aeruginosa more frequently than generally believed. Alternatively, phenotypically distinct strains from a single patient might arise as phenotypic dissociants from a single infecting strain. Because of the frequency and multiplicity of phenotypically distinct P. aeruginosa isolates which we obtained from our cystic fibrosis patients, it is important to select multiple isolates from sputum cultures for antimicrobial susceptibility testing so as to assess adequately the susceptibility of this organism to antibiotic therapy in cystic fibrosis. We recommend that several colonies of each distinguishable colony type of P. aeruginosa be pooled for the antibiogram.

Importance of antimicrobial susceptibility testing of Streptococcus pneumoniae.

Six of 36 strains of Streptococcus pneumoniae isolated in our laboratory during 1977 showed relative resistance to penicillin G. This level of resistance was detectable only by the broth dilution method. Using the disk diffusion method, all six strains appeared susceptible (zone size > 29 mm).