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Oral antibiotic therapy for serious infections in hospitalized patients
January 1978
The Journal of P E D I A T R I C S
175
17~If
Oral antibiotic therapy for serious infections in hospitalized patients
ANTIBIOTICS are seldom given orally to hospitalized children with serious infections. The parenteral route of administration is the most reliable way of ensuring that effective amounts of antibiotic are delivered to the patient. Nevertheless, the surest route is not the safest route. Thrombophlebifis and nosocomial bacteremias are infrequent but do occur in spite of stringent precautions of aseptic technique. If intravenous sites are not changed every 48 hours, the risk of nosocomial infection increases sharply; this is a commonly violated principle of good nursing procedure. When an intravenous infusion is running well, there is a great temptation to ignore the rules and not start a flesh infusion at the prescribed 48hour interval. For many serious infections such as osteomyelitis, bacterial endocarditis, and staphylococcal pneumonia, antibiotic therapy is continued for three weeks or longer. This practice creates technical problems as usable veins vanish, the patient's activities are restricted, and the risks from prolonged indwelling needles or intravenous catheters increase. When an antibiotic is given intravenously, there is a brief period when the concentration in the blood is much higher than that following intramuscular or oral administration, but by one hour after the dose the pharmacokinetics are similar for all three routes of administration. The momentary, very high concentration of antibiotic probably has no vital therapeutic importance. It is impossible to prove or disprove this statement, but general experience indicates that the "area under the curve" of antibiotic concentrations in relation to time is more important than any single peak concentration. We also know from experience that it is not necessary to maintain continuously bactericidal amounts of antibiotic in blood. For example, patients treated with continuous intravenous infusions of penicillin respond no better than those who are given the same daily dosage of penicillin by. intermittent bolus injections every four or six hours. If bactericidal activity is present in blood for at least one to two hours after a dose, the therapeutic response is good even though subinhibitory amounts of antibiotic are present in blood serum about half of every 24 hours.
I t follows logically, then, that oral antibiotic therapy under suitably controlled and monitored conditions can be adequate for treatment of selected serious infections and provides two'gains: lesser risk of nosocomial infection and greater patient comfort. We tested that hypothesis in patients with suppurative arthritis and osteomyelitis and, as reported in detail elsewhere in this issue of TuE JOURNAL, the results were satisfactory. Since that experience we have expanded use of ora! therapy to hospitalized patients with other serious infections such as bacterial endocarditis and pneumonias with empyema, with equally satisfactory results. We have not utilized such therapy on an out-patient basis; though it would be desirable to save the expense of prolonged hospitalization, we have felt that the risks of noncompliance in serious diseases are too great to assume. We can envisage special circumstances in which compliance in out-patients could be assured but, in general, the treatment should be rigidly controlled in the hospital. See related articles, pp. 131 and 135.
Three elements are necessary to carry out a successful oral antibiotic program. (1) Patient compliance. The patient must be able to swallow and retain the medication. A spitting, struggling infant is not a suitable candidate. (2) Coordination with the microbiology laboratory. The laboratory should have the capability of performing tests of serum inhibitory and bactericidal activity. This requires no especial expertise, but it does require having the infecting organism available. Therefore, the laboratory should be informed at the outset that you plan to obtain these tests and that the organism should be saved. (3) Monitoring and adjusting dosage. We recommend parenteral antibiotic therapy for the first three to five days until the situation is under control in terms of knowing culture and antibiotic susceptibility results, and any indicated surgical procedures have been done. The oral dosage of antibiotic is two to three times that given for minor infections and is usually the same as the dosage customarily given parenterally. For penicillin G or V, cephalex-
Vol. 92, No. 1, pp. 175-176
176
Editor's column
in, cloxacillin, dicloxacillin, or amoxicillin we recommend that 100 m g / k g / d a y be started in divided doses every six hours. With ampicillin the initial dosage should be 150 to 200 mg/kg/day. The doses are preferably given on an empty stomaqh to assure maximum, prompt absorption; this is particularly important with ampicillin and penicillin G or V. A serum or plasma specimen is collected one or two hours after a dose and a broth dilution test of serum inhibitory and bactericidal titer determined. For staphylococci and coliform bacilli the serum bactericidal titer should be at least 1:8 and for highly susceptible bacteria, such as pneumococci, it should be at least 1:64. There is a good deal of variability from patient to patient in absorbability of antibiotics. Even with the rather large dosages recommended above we have found it necessary to increase the dosage in 10 to 15% of patients in order to achieve satisfactory serum bactericidal activity. This fact
The Journal of Pediatrics January 1978 emphasizes the importance of monitoring the patients' response and the potential hazard of uncontrolled use of oral antimicrobial therapy. Oral antibiotic therapy for serious infections has deftnite advantages over prolonged parenteral therapy but it cannot be embarked upon casually. The consequences of ineffectual oral antibiotic therapy can be grave. Whenever there is doubt about the appropriateness of oral therapy or whenever suitable monitoring is not possible, it is advisable to conform to tradition and use the parenteral route for antibiotic administration. John D. Nelson, M.D. Department of Pediatrics The University of Texas Southwestern Medical School at Dallas 5323 Harry Hines Blvd. Dallas, T X 75235
The Journal of P E D I A T R I C S
175
17~If
Oral antibiotic therapy for serious infections in hospitalized patients
ANTIBIOTICS are seldom given orally to hospitalized children with serious infections. The parenteral route of administration is the most reliable way of ensuring that effective amounts of antibiotic are delivered to the patient. Nevertheless, the surest route is not the safest route. Thrombophlebifis and nosocomial bacteremias are infrequent but do occur in spite of stringent precautions of aseptic technique. If intravenous sites are not changed every 48 hours, the risk of nosocomial infection increases sharply; this is a commonly violated principle of good nursing procedure. When an intravenous infusion is running well, there is a great temptation to ignore the rules and not start a flesh infusion at the prescribed 48hour interval. For many serious infections such as osteomyelitis, bacterial endocarditis, and staphylococcal pneumonia, antibiotic therapy is continued for three weeks or longer. This practice creates technical problems as usable veins vanish, the patient's activities are restricted, and the risks from prolonged indwelling needles or intravenous catheters increase. When an antibiotic is given intravenously, there is a brief period when the concentration in the blood is much higher than that following intramuscular or oral administration, but by one hour after the dose the pharmacokinetics are similar for all three routes of administration. The momentary, very high concentration of antibiotic probably has no vital therapeutic importance. It is impossible to prove or disprove this statement, but general experience indicates that the "area under the curve" of antibiotic concentrations in relation to time is more important than any single peak concentration. We also know from experience that it is not necessary to maintain continuously bactericidal amounts of antibiotic in blood. For example, patients treated with continuous intravenous infusions of penicillin respond no better than those who are given the same daily dosage of penicillin by. intermittent bolus injections every four or six hours. If bactericidal activity is present in blood for at least one to two hours after a dose, the therapeutic response is good even though subinhibitory amounts of antibiotic are present in blood serum about half of every 24 hours.
I t follows logically, then, that oral antibiotic therapy under suitably controlled and monitored conditions can be adequate for treatment of selected serious infections and provides two'gains: lesser risk of nosocomial infection and greater patient comfort. We tested that hypothesis in patients with suppurative arthritis and osteomyelitis and, as reported in detail elsewhere in this issue of TuE JOURNAL, the results were satisfactory. Since that experience we have expanded use of ora! therapy to hospitalized patients with other serious infections such as bacterial endocarditis and pneumonias with empyema, with equally satisfactory results. We have not utilized such therapy on an out-patient basis; though it would be desirable to save the expense of prolonged hospitalization, we have felt that the risks of noncompliance in serious diseases are too great to assume. We can envisage special circumstances in which compliance in out-patients could be assured but, in general, the treatment should be rigidly controlled in the hospital. See related articles, pp. 131 and 135.
Three elements are necessary to carry out a successful oral antibiotic program. (1) Patient compliance. The patient must be able to swallow and retain the medication. A spitting, struggling infant is not a suitable candidate. (2) Coordination with the microbiology laboratory. The laboratory should have the capability of performing tests of serum inhibitory and bactericidal activity. This requires no especial expertise, but it does require having the infecting organism available. Therefore, the laboratory should be informed at the outset that you plan to obtain these tests and that the organism should be saved. (3) Monitoring and adjusting dosage. We recommend parenteral antibiotic therapy for the first three to five days until the situation is under control in terms of knowing culture and antibiotic susceptibility results, and any indicated surgical procedures have been done. The oral dosage of antibiotic is two to three times that given for minor infections and is usually the same as the dosage customarily given parenterally. For penicillin G or V, cephalex-
Vol. 92, No. 1, pp. 175-176
176
Editor's column
in, cloxacillin, dicloxacillin, or amoxicillin we recommend that 100 m g / k g / d a y be started in divided doses every six hours. With ampicillin the initial dosage should be 150 to 200 mg/kg/day. The doses are preferably given on an empty stomaqh to assure maximum, prompt absorption; this is particularly important with ampicillin and penicillin G or V. A serum or plasma specimen is collected one or two hours after a dose and a broth dilution test of serum inhibitory and bactericidal titer determined. For staphylococci and coliform bacilli the serum bactericidal titer should be at least 1:8 and for highly susceptible bacteria, such as pneumococci, it should be at least 1:64. There is a good deal of variability from patient to patient in absorbability of antibiotics. Even with the rather large dosages recommended above we have found it necessary to increase the dosage in 10 to 15% of patients in order to achieve satisfactory serum bactericidal activity. This fact
The Journal of Pediatrics January 1978 emphasizes the importance of monitoring the patients' response and the potential hazard of uncontrolled use of oral antimicrobial therapy. Oral antibiotic therapy for serious infections has deftnite advantages over prolonged parenteral therapy but it cannot be embarked upon casually. The consequences of ineffectual oral antibiotic therapy can be grave. Whenever there is doubt about the appropriateness of oral therapy or whenever suitable monitoring is not possible, it is advisable to conform to tradition and use the parenteral route for antibiotic administration. John D. Nelson, M.D. Department of Pediatrics The University of Texas Southwestern Medical School at Dallas 5323 Harry Hines Blvd. Dallas, T X 75235