5591
Efficacy of Aztreonam in the Treatment of Neonatal Sepsis S. Sklavunu-Tsurutsoglu, M. Gatzola-Karaveli, K. Hatziioannidis, and G. Tsurutsoglu
From the Second Department of Pediatrics and the First Propedeutic Medical Department, Aristotelian University, AHEPA Hospital, Thessaloniki, Greece
Neonatal sepsis continues to cause substantial morbidity and mortality [1, 2], although reliable statistics are unavailable because the disease is not reportable. Estimates of data from individual institutions reveal that 1-10 infants per 1,000 live births develop sepsis. Although the incidence of sepsis has remained constant during the last 50 years, the predominant pathogens and case-fatality rate have varied considerably from decade to decade. In the first decades of the 20th century, before antimicrobial agents became available, grampositive bacteria were the predominant etiologic ag~nts of neonatal sepsis. In the 1940s and 1950s, gram-negative organisms were implicated in the vast majority of cases. A pandemic of staphylococcal disease in the late 1950s and early 1960s involved newborn populations, and in the mid-1970s, the group B streptococcus emerged as the predominant pathogen in neonatal sepsis in the United States, [2, 3]. The group B streptococcus has not been a major pathogen in Latin America and Asia [2, 3], and in Greece, for example, the great majority of neonatal infections are caused by gram-negative bacteria and only rarely are group B streptococci involved. We based our administration of aztreonam to newborns with sepsis on its proven efficacy in the treatment of gr~-neg~tive bacterial infections, including most pseudomonal infections. The lack both of major adverse effects in adults and in children and of suppression of the host's bacterial flora were considered to be advantages of great importance for treatment of neonates. In addition, aztreonam does not interfere with the binding of bilirubin and albumin and, therefore, does not increase. the risk of bilirubin encephalopathy.
Patients and Methods The characteristics of the 55 neonates enrolled in this open study are outlined in table 1. All neonates were septicemic. Every neonate admitted to the Department of Pediatrics with suspected septicemia underwent a physical examination, and a battery of laboratory tests were performed on specimens obtained during the examination. These tests included cultures of blood, urine (obtained by suprapubic puncture), CSF, swabs of umbilical cord, and nasal, otic, and ophthalmic secretions. A routine examination ofperipheral blood also was performed, with particular attention being paid to the number of leukocytes and thrombocytes and to the presence of band forms. Further urinalysis and measurements oflevels of urea, creatinine, C-reactive protein, and IgM also were performed. Immediately after the specimens were obtained, aztreonam and penicillin were administered empirically. During the treatment period, patient follow-up was conducted systematically, and the findings from the physical examinations were recorded in detail daily. Cultures of blood and other specimens were repeated, whenever possible, every 3-4 days during therapy and again at the end of the treatment. Follow-up included physical examination and laboratory tests that were conducted 15-20 days after the conclusion of the study. Aztreonam (90-125 mg/jkg-d] administered in two or three doses; mean dosage, 110 mg/jkg-dj) was given iv in combination with penicillin (100,000 U/[kg·d], three times daily) to all but one neonate, a 36-day-old infant who received only aztreonam im. The duration of treatment ranged from 6 to 15 days (mean, 10 days). The total dose administered ranged from 900 to 950 mg.
Results Reprints and correspondence: Dr. S. Sklavunu-Tsurutsoglu, 29 Thalitos Street, GR 546 46 Thessaloniki, Greece. Reviews of Infectious Diseases I991;13(Suppl 7):5591-3 © 1991 by The University of Chicago. All rights reserved. 0162-0886/91/1303-0043$02.00
Etiology. The species of gram-negative bacteria isolated were Escherichia coli, Klebsiella species, Enterobacter species, Pseudomonas aeruginosa, and Proteus mirabilis (table 2). All 65 gram-negative isolates (in some cases more than
Downloaded from http://cid.oxfordjournals.org/ at Monash University on September 16, 2015
In Greece the majority of infections that affect the neonatal population are caused by gramnegative bacteria rather than by group B streptococc~ ~s ~n the 1!nited ~tates. !he present stu~y investigated the efficacyof aztreonam, a 13-lactam antibiotic that IS effectiveagamst gram-n~gatIve organisms, in this population. Fifty-five neonates aged 2.hours to 36 days who had se~sls were enrolled in this open study. Laboratory tests were extensive, and follo~-up.s were ~eta~ed. ~z treonam (90-125 mg/lkg-dj) administered in two or three doses was given m combination with penicillin (100,000 U/[kg·dD for 6-15 days. Fifty-two infants were cured, one improv~d., and two did not improve and received other, more effective regimens. Adverse effects were minimal, and tolerance of aztreonam was excellent.
S592
Sklavunu-Tsurutsoglu et al.
Table 1. Characteristics of neonates who were enrolled in the study of aztreonam for treatment of neonatal sepsis.
Discussion 37 17
1 2,757 g (1,540-4,200 g) 4.66 d (2 h-36 d)
Table 2. Gram-negativebacteria that were isolatedfrom neonates with septicemia. No. of isolates*
Escherichia coli Klebsiella species Enterobacter species Pseudomonas aeruginosa Proteus mirabilis
* In many cases more than one bacterial
26 12
11 9
7 species was isolated.
one bacterial species was isolated) were sensitive to aztreonam (inhibition zones at least 22 nun in diameter). In 14 cases, the septicemia was caused by two or more bacterial species, and in five cases it was caused by a combination of a gramnegative organism and an Enterococcus species. In seven presumed cases of neonatal sepsis, the causative organism was not isolated. Efficacy. Of the 55 infants treated with aztreonam in this study, 52 were cured, one improved, and two did not improve. Of the 48 neonates for whom etiology of sepsis was known, 46 were cured, one improved, and one did not respond satisfactorily. Of the seven neonates for whom etiology was unknown, six were cured and one did not improve. On the sixth day of treatment, the premature newborn whose septic condition was definitely improving underwent surgery for duodenal atresia at another hospital. There he received other antibiotics and was finally cured of his infection. The first treatment failure occurred in a premature infant with septicemia due to E. coli, Klebsiella, and Enterobacter, all of which were sensitive to aztreonam. The infant improved initially during the first 5 days of therapy but experienced a relapse on the 10th day. Aztreonam was replaced by another antibiotic at that time. The second treatment failure occurred in a neonate who had been receiving another antibiotic regimen when hospitalized in a provincial hospital after E. coli had been isolated from urine. The infant had signs of septicemia when transferred to our department, although no pathogen was ever isolated. Aztreonam and penicillin were administered; the neonate's condition improved briefly but then worsened, and aztreonam was replaced by other antibiotics. Adverse effects. Aztreonam was well tolerated, and the only adverse reactions were slight, transient increases in the
Data regarding the administration of aztreonam to children are limited primarily to those on the treatment of urinary tract infections and offer little information regarding neonates [4-16]. In 1984 Stutman et al. [13] first administered aztreonam (30 mg/kg iv as a single dose in 3 minutes) to 29 children, 17 of whom were newborns. They concluded that aztreonam could be given safely to children, even to neonates. These authors noted that in the first week of life premature neonates eliminated the drug at the slowest rate, full-term newborns and infants up to 2 years old exhibited similar but more rapid profiles of drug elimination, and children aged between 2 and 12 years eliminated the drug most rapidly. Peak concentrations of aztreonam in serum did not vary significantly with age. The half-life of the drug was inversely related to age. The data of Stutman et al. on the clearance of aztreonam from serum suggested that satisfactory therapeutic levels of aztreonam could be achieved with smaller doses given at longer intervals. In 1985 Stutman et al. [141investigated the effects of aztreonam and six other antibiotics on the binding of bilirubin to human serum albumin in vitro. They concluded that aztreonam does not interfere with the binding of bilirubin and albumin and, consequently, does not increase the levels of free bilirubin. (An increase in the level of unbound [free] bilirubin is known to increase the risk of bilirubin encephalopathy in jaundiced newborns by enhancing redistribution of bilirubin to extravascular sites, including the brain.) A year later Stutman et al. [15]administered aztreonam for 7-14 days to 59 children, six of whom were neonates with serious infections. Cultures of blood, urine, or specimens from other infected sites from 36 of these patients yielded gramnegative aerobic bacteria. Four of the children, including a 1-month-old neonate, were septicemic. Stutman et al. concluded that in this population aztreonam has no additive effect and may be administered for longer periods without eliciting major adverse reactions. They also noted the lack of diarrhea, thrush, and symptoms associated with suppression of the host's flora. Studies that describe the efficacy of aztreonam in eradicating gram-negative bacteria from children are few in number compared with those for adults. No data from systematic observations in newborns are available. In a previous study, we administered aztreonam to 31 children with gram-negative bacterial infections, eight of whom were newborns with septicemia. The results were impressive: 30 of the children were cured of their infection and one did not improve [12]. The results of the previous study led to the present investigation of the systematic use of aztreonam in neonates with septicemia due to gram-negative organisms.
Downloaded from http://cid.oxfordjournals.org/ at Monash University on September 16, 2015
Organism isolated
levels of transaminases in seven infants and of urea in two infants. In no instance was interruption of treatment necessary.
Value
Characteristic Neonate (no.) Full-term Premature Small for date of birth Mean weight (range) Mean age (range)
RID 1991;13 (Suppl 7)
RID 1991;13 (Suppl 7)
Treatment of Neonatal Sepsis with Aztreonam
Conclusions
References 1. Salzer HR, Tenner W, Illievich V, Pollak A. Evaluation on the effect of antibiotic prophylaxis in preterm infants with central venous or umbilical arterial catheters. In: Proceedings of the Eleventh European Congress of Perinatal Medicine. Rome: CIC Edizioni Internazionali s.r.l., 1988:521-5 2. Siegel JD. Neonatal sepsis. Semin Perinatol 1986;9:20-8 3. Freedman RM, Ingram DL, Gross IE, Ehrenkrantz RA, Warshaw JB, Baltimore RS. A half century of neonatal sepsis at Yale, 1928-1978. Am J Dis Child 1981;135:140-4
4. Adam D. Preliminary experience with aztreonam in pediatric infection. Chemioterapia 1985;4(Suppl):97-8 5. Adam D. Aztreonam: European experience in the treatment of pediatric patients with gram-negative infections. Recent Advances in Chemotherapy 1985;9:1387-9 6. Bassetti D, Mengoli C, Luzzati R, Marcer V, Cavalieri S. Impiego clinico dell'aztreonam. Chemioterapia 1984;3(Suppl):48-51 7. Kitamura I, Ogura H. Studies in pediatrics on aztreonam. Jpn J Antibiot 1985;38:3195-216 8. Kline MW, Kaplan SL, Mason EO. Aztreonam therapy of gram-negative infections predominantly of the urinary tract in children. Curr Ther Res 1986;39:625-31 9. Luzzati R, Raimo F. Impiego dell'aztreonam in pediatria. Accornamento Pediatrico 1984;35 :297-300 10. Principi N, Della Villa A, Landoni R, Reali E, Vigano A. Aztreonam in the treatment of urinary tract infections in children. Chemioterapia 1985;4(Suppl):99-101 11. Rusconi F, Assael BM, Bocazzi A, Colombo R, Crossignani RM, Garlaschi L, Rancilio L. Aztreonam in the treatment of severe urinary tract infections in pediatric patients. Antimicrob Agents Chemother 1986;30:310-4 12. Sklavunu-Tsurutsoglu S, Gatzola-Karaveli M, Hitoglu-Makedu A, Paradelis A, Tsurutsoglu G. Aztreonam in gram-negative infections in children. In: Sabbour MS, Cocuzza G, eds.. Proceedings of the Fifth Mediterranean Congress of Chemotherapy. Cairo, 26 October-l November. Chemioterapia 1986;6(Suppl):415-7 13. Stutman H, Marks MI, Swabb EA. Single-dose pharmacokinetics of aztreonam in pediatric patients. Antimicrob Agents Chemother. 1984; 26:196-9 14. Stutman HR, Parker KM, Marks MI. Potential of moxalactam and other new antimicrobial agents for bilirubin-albumin displacement in neonates. Pediatrics 1985;75:294-8 15. Stutman HR, Chartrand SA, Tolentino T, Friedhoff L, Marks MI. Aztreonam therapy for serious gram-negative infections in children. Am J Dis Child 1986;140:1147-51 16. Terragna A, Giacchino R, Viscoli C, Consani G. Employment of azthreonam in generalized and localized infections determined by gram negative bacteria. G Ital Chemioter 1985;32:423-5
Downloaded from http://cid.oxfordjournals.org/ at Monash University on September 16, 2015
Aztreonam proved to be an excellent therapeutic agent in the present study. Of the 55 infants who underwent treatment, 52 were cured, one improved, and only two did not respond satisfactorily. It should be emphasized, in light of the fact that some strains of Pseudomonas are resistant to aztreonam, that the nine patients with septicemia due to P. aeruginosa were successfully treated with aztreonam. The absence of any major adverse effects was remarkable. Small, transient increases in the levels of transaminases in seven infants were noted, a reaction noted in adults and older children and commonly observed with {3-lactamantibiotics. In two other patients, slight, transient increases in the levels of urea were noted, but these increases could have been caused by the septicemia itself. These mild abnormalities were not clinically significant, and did not necessitate an adjustment in treatment. In conclusion, the advantages of aztreonam, i.e., that it does not cause significant adverse effects, suppress bacterial flora, produce ototoxicity, or increase the levels of free bilirubin, make it an attractive antibiotic for the treatment of gramnegative bacterial infections in neonates.
S593
Efficacy of Aztreonam in the Treatment of Neonatal Sepsis S. Sklavunu-Tsurutsoglu, M. Gatzola-Karaveli, K. Hatziioannidis, and G. Tsurutsoglu
From the Second Department of Pediatrics and the First Propedeutic Medical Department, Aristotelian University, AHEPA Hospital, Thessaloniki, Greece
Neonatal sepsis continues to cause substantial morbidity and mortality [1, 2], although reliable statistics are unavailable because the disease is not reportable. Estimates of data from individual institutions reveal that 1-10 infants per 1,000 live births develop sepsis. Although the incidence of sepsis has remained constant during the last 50 years, the predominant pathogens and case-fatality rate have varied considerably from decade to decade. In the first decades of the 20th century, before antimicrobial agents became available, grampositive bacteria were the predominant etiologic ag~nts of neonatal sepsis. In the 1940s and 1950s, gram-negative organisms were implicated in the vast majority of cases. A pandemic of staphylococcal disease in the late 1950s and early 1960s involved newborn populations, and in the mid-1970s, the group B streptococcus emerged as the predominant pathogen in neonatal sepsis in the United States, [2, 3]. The group B streptococcus has not been a major pathogen in Latin America and Asia [2, 3], and in Greece, for example, the great majority of neonatal infections are caused by gram-negative bacteria and only rarely are group B streptococci involved. We based our administration of aztreonam to newborns with sepsis on its proven efficacy in the treatment of gr~-neg~tive bacterial infections, including most pseudomonal infections. The lack both of major adverse effects in adults and in children and of suppression of the host's bacterial flora were considered to be advantages of great importance for treatment of neonates. In addition, aztreonam does not interfere with the binding of bilirubin and albumin and, therefore, does not increase. the risk of bilirubin encephalopathy.
Patients and Methods The characteristics of the 55 neonates enrolled in this open study are outlined in table 1. All neonates were septicemic. Every neonate admitted to the Department of Pediatrics with suspected septicemia underwent a physical examination, and a battery of laboratory tests were performed on specimens obtained during the examination. These tests included cultures of blood, urine (obtained by suprapubic puncture), CSF, swabs of umbilical cord, and nasal, otic, and ophthalmic secretions. A routine examination ofperipheral blood also was performed, with particular attention being paid to the number of leukocytes and thrombocytes and to the presence of band forms. Further urinalysis and measurements oflevels of urea, creatinine, C-reactive protein, and IgM also were performed. Immediately after the specimens were obtained, aztreonam and penicillin were administered empirically. During the treatment period, patient follow-up was conducted systematically, and the findings from the physical examinations were recorded in detail daily. Cultures of blood and other specimens were repeated, whenever possible, every 3-4 days during therapy and again at the end of the treatment. Follow-up included physical examination and laboratory tests that were conducted 15-20 days after the conclusion of the study. Aztreonam (90-125 mg/jkg-d] administered in two or three doses; mean dosage, 110 mg/jkg-dj) was given iv in combination with penicillin (100,000 U/[kg·d], three times daily) to all but one neonate, a 36-day-old infant who received only aztreonam im. The duration of treatment ranged from 6 to 15 days (mean, 10 days). The total dose administered ranged from 900 to 950 mg.
Results Reprints and correspondence: Dr. S. Sklavunu-Tsurutsoglu, 29 Thalitos Street, GR 546 46 Thessaloniki, Greece. Reviews of Infectious Diseases I991;13(Suppl 7):5591-3 © 1991 by The University of Chicago. All rights reserved. 0162-0886/91/1303-0043$02.00
Etiology. The species of gram-negative bacteria isolated were Escherichia coli, Klebsiella species, Enterobacter species, Pseudomonas aeruginosa, and Proteus mirabilis (table 2). All 65 gram-negative isolates (in some cases more than
Downloaded from http://cid.oxfordjournals.org/ at Monash University on September 16, 2015
In Greece the majority of infections that affect the neonatal population are caused by gramnegative bacteria rather than by group B streptococc~ ~s ~n the 1!nited ~tates. !he present stu~y investigated the efficacyof aztreonam, a 13-lactam antibiotic that IS effectiveagamst gram-n~gatIve organisms, in this population. Fifty-five neonates aged 2.hours to 36 days who had se~sls were enrolled in this open study. Laboratory tests were extensive, and follo~-up.s were ~eta~ed. ~z treonam (90-125 mg/lkg-dj) administered in two or three doses was given m combination with penicillin (100,000 U/[kg·dD for 6-15 days. Fifty-two infants were cured, one improv~d., and two did not improve and received other, more effective regimens. Adverse effects were minimal, and tolerance of aztreonam was excellent.
S592
Sklavunu-Tsurutsoglu et al.
Table 1. Characteristics of neonates who were enrolled in the study of aztreonam for treatment of neonatal sepsis.
Discussion 37 17
1 2,757 g (1,540-4,200 g) 4.66 d (2 h-36 d)
Table 2. Gram-negativebacteria that were isolatedfrom neonates with septicemia. No. of isolates*
Escherichia coli Klebsiella species Enterobacter species Pseudomonas aeruginosa Proteus mirabilis
* In many cases more than one bacterial
26 12
11 9
7 species was isolated.
one bacterial species was isolated) were sensitive to aztreonam (inhibition zones at least 22 nun in diameter). In 14 cases, the septicemia was caused by two or more bacterial species, and in five cases it was caused by a combination of a gramnegative organism and an Enterococcus species. In seven presumed cases of neonatal sepsis, the causative organism was not isolated. Efficacy. Of the 55 infants treated with aztreonam in this study, 52 were cured, one improved, and two did not improve. Of the 48 neonates for whom etiology of sepsis was known, 46 were cured, one improved, and one did not respond satisfactorily. Of the seven neonates for whom etiology was unknown, six were cured and one did not improve. On the sixth day of treatment, the premature newborn whose septic condition was definitely improving underwent surgery for duodenal atresia at another hospital. There he received other antibiotics and was finally cured of his infection. The first treatment failure occurred in a premature infant with septicemia due to E. coli, Klebsiella, and Enterobacter, all of which were sensitive to aztreonam. The infant improved initially during the first 5 days of therapy but experienced a relapse on the 10th day. Aztreonam was replaced by another antibiotic at that time. The second treatment failure occurred in a neonate who had been receiving another antibiotic regimen when hospitalized in a provincial hospital after E. coli had been isolated from urine. The infant had signs of septicemia when transferred to our department, although no pathogen was ever isolated. Aztreonam and penicillin were administered; the neonate's condition improved briefly but then worsened, and aztreonam was replaced by other antibiotics. Adverse effects. Aztreonam was well tolerated, and the only adverse reactions were slight, transient increases in the
Data regarding the administration of aztreonam to children are limited primarily to those on the treatment of urinary tract infections and offer little information regarding neonates [4-16]. In 1984 Stutman et al. [13] first administered aztreonam (30 mg/kg iv as a single dose in 3 minutes) to 29 children, 17 of whom were newborns. They concluded that aztreonam could be given safely to children, even to neonates. These authors noted that in the first week of life premature neonates eliminated the drug at the slowest rate, full-term newborns and infants up to 2 years old exhibited similar but more rapid profiles of drug elimination, and children aged between 2 and 12 years eliminated the drug most rapidly. Peak concentrations of aztreonam in serum did not vary significantly with age. The half-life of the drug was inversely related to age. The data of Stutman et al. on the clearance of aztreonam from serum suggested that satisfactory therapeutic levels of aztreonam could be achieved with smaller doses given at longer intervals. In 1985 Stutman et al. [141investigated the effects of aztreonam and six other antibiotics on the binding of bilirubin to human serum albumin in vitro. They concluded that aztreonam does not interfere with the binding of bilirubin and albumin and, consequently, does not increase the levels of free bilirubin. (An increase in the level of unbound [free] bilirubin is known to increase the risk of bilirubin encephalopathy in jaundiced newborns by enhancing redistribution of bilirubin to extravascular sites, including the brain.) A year later Stutman et al. [15]administered aztreonam for 7-14 days to 59 children, six of whom were neonates with serious infections. Cultures of blood, urine, or specimens from other infected sites from 36 of these patients yielded gramnegative aerobic bacteria. Four of the children, including a 1-month-old neonate, were septicemic. Stutman et al. concluded that in this population aztreonam has no additive effect and may be administered for longer periods without eliciting major adverse reactions. They also noted the lack of diarrhea, thrush, and symptoms associated with suppression of the host's flora. Studies that describe the efficacy of aztreonam in eradicating gram-negative bacteria from children are few in number compared with those for adults. No data from systematic observations in newborns are available. In a previous study, we administered aztreonam to 31 children with gram-negative bacterial infections, eight of whom were newborns with septicemia. The results were impressive: 30 of the children were cured of their infection and one did not improve [12]. The results of the previous study led to the present investigation of the systematic use of aztreonam in neonates with septicemia due to gram-negative organisms.
Downloaded from http://cid.oxfordjournals.org/ at Monash University on September 16, 2015
Organism isolated
levels of transaminases in seven infants and of urea in two infants. In no instance was interruption of treatment necessary.
Value
Characteristic Neonate (no.) Full-term Premature Small for date of birth Mean weight (range) Mean age (range)
RID 1991;13 (Suppl 7)
RID 1991;13 (Suppl 7)
Treatment of Neonatal Sepsis with Aztreonam
Conclusions
References 1. Salzer HR, Tenner W, Illievich V, Pollak A. Evaluation on the effect of antibiotic prophylaxis in preterm infants with central venous or umbilical arterial catheters. In: Proceedings of the Eleventh European Congress of Perinatal Medicine. Rome: CIC Edizioni Internazionali s.r.l., 1988:521-5 2. Siegel JD. Neonatal sepsis. Semin Perinatol 1986;9:20-8 3. Freedman RM, Ingram DL, Gross IE, Ehrenkrantz RA, Warshaw JB, Baltimore RS. A half century of neonatal sepsis at Yale, 1928-1978. Am J Dis Child 1981;135:140-4
4. Adam D. Preliminary experience with aztreonam in pediatric infection. Chemioterapia 1985;4(Suppl):97-8 5. Adam D. Aztreonam: European experience in the treatment of pediatric patients with gram-negative infections. Recent Advances in Chemotherapy 1985;9:1387-9 6. Bassetti D, Mengoli C, Luzzati R, Marcer V, Cavalieri S. Impiego clinico dell'aztreonam. Chemioterapia 1984;3(Suppl):48-51 7. Kitamura I, Ogura H. Studies in pediatrics on aztreonam. Jpn J Antibiot 1985;38:3195-216 8. Kline MW, Kaplan SL, Mason EO. Aztreonam therapy of gram-negative infections predominantly of the urinary tract in children. Curr Ther Res 1986;39:625-31 9. Luzzati R, Raimo F. Impiego dell'aztreonam in pediatria. Accornamento Pediatrico 1984;35 :297-300 10. Principi N, Della Villa A, Landoni R, Reali E, Vigano A. Aztreonam in the treatment of urinary tract infections in children. Chemioterapia 1985;4(Suppl):99-101 11. Rusconi F, Assael BM, Bocazzi A, Colombo R, Crossignani RM, Garlaschi L, Rancilio L. Aztreonam in the treatment of severe urinary tract infections in pediatric patients. Antimicrob Agents Chemother 1986;30:310-4 12. Sklavunu-Tsurutsoglu S, Gatzola-Karaveli M, Hitoglu-Makedu A, Paradelis A, Tsurutsoglu G. Aztreonam in gram-negative infections in children. In: Sabbour MS, Cocuzza G, eds.. Proceedings of the Fifth Mediterranean Congress of Chemotherapy. Cairo, 26 October-l November. Chemioterapia 1986;6(Suppl):415-7 13. Stutman H, Marks MI, Swabb EA. Single-dose pharmacokinetics of aztreonam in pediatric patients. Antimicrob Agents Chemother. 1984; 26:196-9 14. Stutman HR, Parker KM, Marks MI. Potential of moxalactam and other new antimicrobial agents for bilirubin-albumin displacement in neonates. Pediatrics 1985;75:294-8 15. Stutman HR, Chartrand SA, Tolentino T, Friedhoff L, Marks MI. Aztreonam therapy for serious gram-negative infections in children. Am J Dis Child 1986;140:1147-51 16. Terragna A, Giacchino R, Viscoli C, Consani G. Employment of azthreonam in generalized and localized infections determined by gram negative bacteria. G Ital Chemioter 1985;32:423-5
Downloaded from http://cid.oxfordjournals.org/ at Monash University on September 16, 2015
Aztreonam proved to be an excellent therapeutic agent in the present study. Of the 55 infants who underwent treatment, 52 were cured, one improved, and only two did not respond satisfactorily. It should be emphasized, in light of the fact that some strains of Pseudomonas are resistant to aztreonam, that the nine patients with septicemia due to P. aeruginosa were successfully treated with aztreonam. The absence of any major adverse effects was remarkable. Small, transient increases in the levels of transaminases in seven infants were noted, a reaction noted in adults and older children and commonly observed with {3-lactamantibiotics. In two other patients, slight, transient increases in the levels of urea were noted, but these increases could have been caused by the septicemia itself. These mild abnormalities were not clinically significant, and did not necessitate an adjustment in treatment. In conclusion, the advantages of aztreonam, i.e., that it does not cause significant adverse effects, suppress bacterial flora, produce ototoxicity, or increase the levels of free bilirubin, make it an attractive antibiotic for the treatment of gramnegative bacterial infections in neonates.
S593
