Biomedical subjects
Publications and source records attributed to R I Goldenberg.
The therapy of osteomyelitis utilizing 481 courses of intravenous antibiotics in outpatients was analyzed to identify the types of bone infection most frequently treated by this form of therapy. The efficacy of this form of treatment is also discussed.
Recent articles promoting the advantages of intravenous antibiotic therapy and total parenteral nutrition for use in home health care patients have spawned a multitude of commercial and hospital-based programs dedicated to providing such therapies in outpatient settings. Only since the establishment of these programs has there evolved an increasing familiarity with adverse experiences and pitfalls in the provision of outpatient care. Significant errors have been made in the areas of patient and disease admission criteria, antibiotic regimens, medicolegal concepts, medical and hospital politics, and financial reimbursement. This article explores the pitfalls intrinsic to the delivery of outpatient parenteral therapies and focuses on the need for diligence in program coordination, multidisciplinary involvement, and education in averting those pitfalls.
The combined medical-surgical approach to therapy for osteomyelitis requires patients to receive intravenous antibiotics three to six times daily for 4 to 6 weeks after initial surgical debridement. The greatly extended half-life of the new cephalosporin, ceftriaxone (6 to 8 hours), enabled its intravenous administration once or twice daily to 76 patients for the treatment of osteomyelitis. Cure or improvement was noted in 66 of the 76 patients (87 percent). Most of the failures occurred in the group of patients with osteomyelitis complicated by vascular insufficiency. The once or twice daily dosing possible with ceftriaxone was particularly advantageous for permitting highly cost-effective at home therapy for 42 of the 76 patients.
Patients who participated in an outpatient intravenous therapy program designed to limit hospitalization for those who could be maintained on ceftriaxone at home were interviewed regarding costs and benefits. Of the 79 patients interviewed concerning 83 therapeutic episodes, 43.4 percent were able to perform their usual activities as soon as they began the program, 28.9 percent were restricted for part of the time, and 27.7 percent never resumed their usual activities. The 83 therapeutic episodes represent a total of 2,409 outpatient days (mean 29.7; standard deviation [SD] 17.7), 1,406 of which represent unrestricted activities. Costs and benefits of the program were calculated separately for four employment groups: not employed; usually employed, but not while on intravenous therapy; employed while on intravenous therapy, with time off for follow-up visits; and employed while on intravenous therapy, no time off for follow-up required. The mean total benefit, weighted across all four groups, was $6,588.14 (SD = $3,802.90) per patient. Mean weighted costs totalled $1,768.02 (SD = $1,129.36). The overall weighted benefit/cost ratio was approximately 5:1. Although private insurers reimbursed 63 percent of the patients for all hospitalization costs, only 39 percent were fully covered for the follow-up physician visits required during outpatient therapy.
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Ceftriaxone, a broad spectrum cephalosporin with a markedly extended half-life, was administered to 68 patients with 71 infections in an open trial. Sixty-three infections (89%) had a satisfactory clinical response with eradication of bacteria present at the initiation of therapy in 62 infections (87%). The eight treatment failures correlated well with the development of resistance to ceftriaxone during therapy in Enterobacter and Pseudomonas species (two cases) and with superinfection with Bacteroides fragilis (three cases). Treatment was discontinued in eight patients because of unwanted effects. Serious side effects included leukopenia, rash, fever, and enterocolitis.
Ceftazidime was administered to 41 patients with serious infections caused by Pseudomonas aeruginosa (24 cases) and other bacteria (17 cases). The clinical response rate of pseudomonas infections (88%) was similar to that of other bacteria (94%) with microbiological eradication of 83% of initial pseudomonas isolates compared to 82% of non-pseudomonas strains. The development of resistance to ceftazidime during therapy was observed in 3 cases (Enterobacter agglomerans, Enterobacter cloacae, and Ps. aeruginosa), and superinfection by a resistant Enterobacter agglomerans occurred in one case. Adverse reactions of clinical significance included two cases of leukopenia and one case each of azotaemia, diarrhoea (Clostridium difficile toxin positive), and rash.
Piperacillin, a new broad spectrum semisynthetic penicillin derivative, was administered to 22 patients with 25 Pseudomonas aeruginosa infections. All initially responded favorably, although five complicated urinary tract infections and two infections involving prostheses relapsed. In 15 cases, microbiologic eradication of the Pseudomonas was achieved. Failure to achieve a clinical cure was correlated in all cases with the inability to eradicate the organism, which was the result of development of in vitro resistance to piperacillin during therapy (four cases) and of underlying disease impairing host responses. Adverse reactions to piperacillin included leukopenia (eight cases) and nephrotoxicity (two cases).
Ceftazidime, a new broad-spectrum cephalosporin, was administered to 30 patients with serious bacterial infections in a randomized dosing trial with daily doses of 1.5 or 3 g. Both regimens were equally efficacious, with satisfactory clinical responses in 28 instances (93%) and microbiological eradication of 79% of initial bacterial isolates. The development of resistance to ceftazidime during therapy was observed in three cases (Enterobacter agglomerans, Enterobacter cloacae, and Pseudomonas aeruginosa) and superinfection by a resistant Enterobacter agglomerans strain occurred in one case. Adverse reactions of clinical significance included one case each of leukopenia, azotemia, diarrhea (Clostridium difficile toxin positive), and rash.
Ceftriaxone, a broad-spectrum cephalosporin with a markedly extended half-life, was administered to 100 patients with 56 bone and 44 soft tissue infections. Sixty-eight received 1 g twice daily, and 32 received 2 g once daily intravenously. Overall, 91% had a satisfactory clinical response, with similar efficacies in both treatment regimens. In six patients, failure to achieve a cure correlated well with the development of resistance to ceftriaxone during therapy in Enterobacter and Pseudomonas species (two cases) and with superinfection with Bacteroides fragilis (four cases). In 41 patients, intravenous drug therapy was continued after discharge from the hospital. In this group, 1,093 patient-days of hospitalization were saved, amounting to $150,020 in cost savings. The prolonged half-life facilitated the administration of ceftriaxone in this setting.
Imipenem (formerly imipemide, N-formimidoyl thienamycin, or MK0787) was compared to moxalactam in a randomized therapeutic trial involving 39 evaluable patients with serious bacterial infections. Of those treated with imipenem, 89% were cured or improved versus 60% for moxalactam (P = 0.06). Although mucocutaneous fungal infections occurred in both groups (25 and 10%, respectively), Streptococcus faecalis superinfection was seen in two patients in the moxalactam group only. Adverse drug reactions occurred with both drugs, although bleeding occurred in three patients treated with moxalactam.
A program has been developed for the outpatient administration of parenteral antibiotics. To date, more than 150 patients with osteomyelitis, septic arthritis, pyelonephritis, endocarditis, and other infections have been treated. Antibiotic solutions were prepared in the hospital pharmacy and given to the patient to be kept refrigerated at home until used. Patients administered their own antibiotics by means of a heparin lock, which was replaced every four days or when necessary. Complications were infrequent. Many patients were able to return to work while receiving therapy; others enjoyed the comfort of being at home. Cost reductions were substantial, calculated to be at least $142 a day, or the charge for a semiprivate room in 1981. In addition to the cost savings, critically needed hospital beds were freed for more acutely ill patients.
Ampicillin-resistant strains are presently known to account for 10% to 20% of type b Haemophilus influenzae infections in the United States. To determine whether the incidence in a community hospital parallels that of several university hospitals, we reviewed medical records of the 99 children with type b Haemophilus systemic infections for the period 1976 to 1979. These cass represented 1.8% of all pediatric medical admissions. In 1976-1977, 5% of those infections were caused by resistant strains; the incidence increased to 19% for the period 1978-1979. This increase on a community hospital level parallels the increase in ampicillin resistance in Haemophilus noted in university hospitals and underscores the need for chloramphenicol (alone or in combination with ampicillin) as initial treatment for systemic Haemophilus infections.
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A newborn infant with hyaline membrane disease and aspiration pneumonia developed purulent meningitis on day 19, three days after discontinuation of ampicillin sodium and gentamicin sulfate therapy. Therapy with gentamicin, both systemically and intrathecally, for two weeks was ineffective. During this time each of four specimens of cerebrospinal fluid contained two serotypes of Escherichia coli, namely, O83:H4 and O75:H5. The antibiograms of the two strains were identical, both being susceptible to gentamicin and ampicillin. Treatment with ampicillin resulted in prompt disappearance of the infecting microorganisms and recovery from the infection. One of the strains (O75:H5) produced an antigen cross-reacting with the capsular antigen of Haemophilus influenzae type B; the other did not. The patient developed O antibodies in substantial titers against E coli O83 but not against E coli O75.
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Eighty-nine pediatric patients (median age, 12.0; range, 1.5 to 18 years) were treated with antibiotics given intravenously by self- or parent administration for a variety of infections, under close physician supervision. Patients with infections involving bone and joint (53), respiratory tract (16), soft tissue (9), abdominal cavity (4), genitourinary tract (4) and bloodstream (3) were treated for a mean period of 19.0 days. Staphylococcus aureus, Pseudomonas aeruginosa and Haemophilus influenzae were the most frequent pathogens. Favorable clinical outcomes occurred in 85 patients (96%). Adverse clinical and laboratory events occurred at a frequency commensurate with that of hospitalized patients. A total of 1700 patient days were managed in this outpatient setting at significant cost savings, and the method allowed early return to school for 83 patients (93%). Intravenous antibiotic therapy in ambulatory patients can provide a successful, safe, cost-effective alternative to inpatient care under conditions of diligent patient screening and physician-centered follow-up.