Kegg Pathway: Cephalosporins - parenteral agents

Recenti Prog Med. 2008 Jul-Aug; 99(7-8): 343-6
Montini G

Urinary tract infection (UTI) is one of the most common bacterial infections in infancy, its prevalence being 5% in febrile infants (2 to 24 months of age). 10 to 20% of febrile UTIs may result in permanent renal damage (scar), whose long-term significance (hypertension or proteinuria) in previously normal kidneys remains unclear. A wide variety of antibiotic agents have been used, generally administered aggressively by intravenous route and for long periods (up to three weeks), to possibly prevent scar formation and/or sepsis complications. Recent studies suggest that children with febrile UTIs can be effectively treated with oral antibiotics such as cefixime or amoxycillin/clavulanic acid for 10 to 14 days.

Intern Med. 2008; 47(11): 995-1001
Gul HC, Erdem H, Gorenek L, Ozdag MF, Kalpakci Y, Avci IY, Besirbellioglu BA, Eyigun CP

OBJECTIVE: The central nervous system involvement of Brucellosis causes a hard to treat infection with multiple sequelae. The aim of this paper is to discuss the course of neurobrucellosis in response to therapy. PATIENTS AND METHODS: Patients with neurobrucellosis were evaluated. The diagnosis was established by the isolation of bacteria, abnormal CSF findings and positive serology. Ceftriaxone, rifampicin, doxycycline and trimethoprim sulfamethoxazole were the antibiotic choices for these cases. RESULTS: We present 11 cases with neurobrucellosis. None of our patients died, albeit one case has a critical situation due to subarachnoid hemorrhage and its' concordant sequelae. Only one of four patients with walking difficulty and two with hearing loss were normalized with therapy. Imaging techniques did not provide any specific contribution regarding the Brucella infection. CONCLUSIONS: parenteral ceftriaxone should be used as an initial alternative in the management of neurobrucellosis. Although the therapy should be individualized, the duration of therapy should be a minimum of six months with suitable antibiotics.

Am J Obstet Gynecol. 2008 May; 198(5): e54-6
Ehsanipoor RM, Chung JH, Clock CA, McNulty JA, Wing DA

OBJECTIVE: The purpose of this study was to compare the efficacy and outcomes of 2 different antibiotic regimens that are used to prolong latency in preterm premature rupture of membranes. The primary objective was to determine whether the use of ampicillin-sulbactam/amoxicillin + clavulanate was associated with an increased risk of necrotizing enterocolitis. STUDY DESIGN: A retrospective review of pregnancies that were complicated by preterm premature rupture of membranes from 1999-2006 at 2 institutions was performed. Outcomes were compared between subjects who received parenteral ampicillin-sulbactam followed by oral amoxicillin + clavulanate (protocol A) and subjects who received parenteral cefazolin and erythromycin followed by oral cephalexin and erythromycin (protocol B). RESULTS: There were 147 women who were evaluated; 88 women received protocol A, and 59 women received protocol B. There were no differences in latency period, gestational age at delivery, or route of delivery. The incidence of necrotizing enterocolitis was 8.0% and 10.2% for protocol A and protocol B, respectively (P = .64). CONCLUSION: Ampicillin-sulbactam/amoxicillin + clavulanate was not associated with an increase in neonatal necrotizing enterocolitis. Erythromycin in combination with cefazolin and cephalexin is an effective latency antibiotic regimen.

Trop Anim Health Prod. 2008 Feb; 40(2): 93-9
El-Khodery SA, Osman SA

This report was delineated to study the clinical, bacteriological and therapeutic aspects concerned with acute coliform mastitis in buffaloes. Bacteriological examination of 80 quarter milk samples obtained aseptically from 56 buffaloes with acute mastitis revealed that coliform bacteria was the most common pathogen (45 cases) followed by Staphylococcus aureus (seven cases) then Streptococcus uberis (three cases), and Streptococcus agalactiae (one case). Clinically, hotness, swelling and painful reaction with serous excretion containing clots was recorded in buffaloes with coliform mastitis. The efficacy of ceftiofur was evaluated in the treatment of buffaloes with acute coliform mastitis. parenteral ceftiofur neither improved clinical signs nor returned milk to pre-infection production level, whereas intramammary ceftiofur and combination of intramammary with parenteral ceftiofur improved the clinical signs in 10/15 and 12/15 buffaloes, respectively. On quarter level, 3/17, 12/17 and 15/21 quarters recovered in groups received parenteral, intramammary and combination therapy, respectively. This study demonstrates that systemic ceftofur is not effective in the treatment of clinical coliform mastitis in buffaloes.

J AOAC Int. 2008 Jan-Feb; 91(1): 59-66
Schmidt CA, Carazzo M, Laporta LV, Bittencourt CF, Santos MR, Friedrich M

Ceftazidime (CFZ) is a broad spectrum parenteral beta-lactam antibiotic of the cephalosporin family. This paper reports the development and validation of an agar diffusion microbiological assay using the cylinder-plate method for determination of CFZ in powder for injection. The validation carried out yielded good results in terms of linearity, precision, accuracy, selectivity, and robustness. The assay is based on the inhibitory effect of CFZ upon the strain of Pseudomonas aeruginosa ATCC 27853 used as the test microorganism. The results of the assays were treated statistically by analysis of variance and were found to be linear (correlation coefficient = 0.999998) in the selected range of 8.0-32.0 microg/mL; precise [repeatability: relative standard deviation (RSD) = 1.11%; intermediate precision: between-day RSD = 1.37% and between-analyst RSD = 1.41%]; and accurate. The selectivity of the bioassay was evaluated by analysis of degraded samples at 50 degrees C, and the results were compared with a pharmacopeial liquid chromatographic method at the time 0, 24, and 48 h. The results demonstrated the validity of the proposed bioassay, which allows reliable quantitation of CFZ in pharmaceutical samples and can be used as a useful alternative methodology for CFZ analysis in routine quality control.

Orv Hetil. 2008 Mar 30; 149(13): 597-600
Ludwig E

Urinary tract infections are more frequent in diabetic patients than in non-diabetics, or take a more severe course. The difference is more pronounced in women both in symptomatic infections and asymptomatic bacteriuria. The spectrum of pathogens is similar to that of non-diabetic patients. In case of cystitis, the treatment strategy the same that is recommended in non-diabetic patients (due to lack of clinical trials) but because of the more frequent renal involvement a highly effective antibiotic therapy is suggested. In pyelonephritis, parenteral therapy and close observation are recommended that may require hospitalisation. The administration of doxycycline or cotrimoxazole is not recommended in empiric therapy because of the high resistance rate of E. coli , but even the choice of amoxycillin/clavulanic acid or a fluoroquinolone is questionable for empiric therapy in severe infections. At present, the most effective oral antibiotics are the 3. generation Cephalosporins. Routine screening of bacteriuria is not recommended in diabetic patients, the administration of antibiotic does not prevent the further symptomatic episodes.

Arch Intern Med. 2008 Feb 25; 168(4): 357-62
D'Agata E, Mitchell SL

BACKGROUND: Nursing home residents with advanced dementia are at high risk of infections and antimicrobial exposure near the end of life. Detailed studies quantifying antimicrobial prescribing practices among these residents have not been performed. METHODS: A cohort of 214 residents with advanced dementia from 21 Boston-area nursing homes were followed up prospectively for 18 months or until death. We analyzed antimicrobial use, including type, indication, and quantity, by days of therapy per 1000 resident-days. RESULTS: During an average of 322 days of follow-up, 142 residents (66.4%) with advanced dementia received at least 1 course of antimicrobial therapy (mean [SD] number of courses per resident, 4.0 [3.7]). The mean (SD) number of days of therapy per 1000 resident-days for the entire cohort was 53.0 (4.3). Quinolones and third-generation Cephalosporins were the most commonly prescribed antimicrobials, accounting for 38.3% and 15.2%, respectively, of 540 prescribed antimicrobial therapy courses. A respiratory tract infection was the most common indication (46.7% of all antimicrobial therapy courses). Among 99 decedents, 42 (42.4%) received antimicrobials during the 2 weeks before death, of which 30 of 72 courses (41.7%) were administered via the parenteral route. The number of decedents receiving antimicrobials (P < .001), the number of antimicrobials prescribed (P = .01), and the days of therapy per 1000 resident-days (P < .001) increased significantly as subjects approached death. CONCLUSIONS: Persons with advanced dementia are frequently exposed to antimicrobials, especially during the 2 weeks before death. The implications of this practice from the perspective of the individual treatment burden near the end of life and its contribution to the emergence of antimicrobial resistance in the nursing home setting need further evaluation.

S Afr Med J. 2007 Nov; 97(11): 1133-1140
Jacobs MR

Despite increasing resistance in the pneumococcus over the past 30 years, there are few cases of treatment failure of non-meningeal infections with high-dosage parenteral penicillin G, which still remains highly effective for many pneumococcal diseases. This is reflected by the new 2008 CLSI breakpoints for parenteral penicillin G of susceptible, /=8 microg ml, for non-meningeal infections. For meningitis and oral penicillin V use, the old penicillin breakpoints of susceptible, /=2 microg/ml, will remain in place. Clinically relevant susceptibility breakpoints have also been developed for virtually all relevant antimicrobial agents used to treat pneumococcal diseases, based on clinical studies and pharmacokinetic and pharmacodynamic parameters. Although pneumococcal resistance to beta-lactams, macrolides and co-trimoxazole is now common worldwide, we are still able to treat almost all pneumococcal infections adequately. An exception is the oral treatment of multidrug-resistant serotype 19A strains in children in the USA, as these are resistant to amoxicillin, oral Cephalosporins, macrolides, clindamycin and co-trimoxazole. While there is a need to develop new agents, judicious use of antimicrobial agents is the best long-term approach. Empiric treatment guidelines should reflect the emerging threats from increased drug resistance and the possibility of increased virulence in replacement serotypes following vaccine use. Compliance with guidelines by physicians and patients is important to prevent further development of resistance.

Perit Dial Int. 2008 Jan-Feb; 28(1): 96-7
Altay M, Akay H, Yildiz E, Duranay M

Surg Infect (Larchmt). 2007 Dec; 8(6): 567-74
Mazo S, Emparan C, Vallejo M, Soriano P

BACKGROUND: A growing number of surgical infections can be treated safely and effectively with parenteral antimicrobial therapy in the patient's home. Our objective was to define the economic impact of a hospital-in-the-home unit (HITH) introduced into a surgical unit. METHODS: Patients admitted to the HITH must be assessed thoroughly for suitability, including clinical stability and social circumstances, and both patient and caregiver consent must be obtained. The HITH received all stable surgical patients with complicated infections and an expected long-term stay. A total of 150 patients were enrolled during a 12-month period. Patients were reviewed daily to monitor the progress of therapy and check for possible complications. Antibiotic selection was based on appropriate prescribing principles rather than dosing convenience. Innovative dosing regimens were included, such as once-daily aminoglycosides, continuous-infusion beta-lactams, once- or twice-daily Cephalosporins, and oral fluoroquinolones in order to provide effective therapy for a wide range of infections that previously would have required in-hospital care. Economic efficiency for both the surgical and the HITH unit was assessed by examining Diagnosis-Related Group (DRG)-based clinical processes, profits and losses of each clinical process, and a quantitative model for performance evaluation and benchmarking (data envelopment analysis; DEA). RESULTS: The mean stay in the surgical unit was decreased (3.95 days) while increasing the case mix (1.42). At the same time, HITH patients had a mean stay of 8.69 days with a stable case mix of 1.61. The economic benefit of both units increased in the surgical unit because of a shorter stay and in the HITH secondary to greater impact of the case mix while maintaining the mean stay. CONCLUSIONS: Appropriate use of HITH leads to greater patient and caregiver satisfaction, efficient in-hospital bed use, and financial efficiencies. Patients receiving intravenous antibiotics, wound care, parenteral nutrition, or transfusions do not always need to be in the hospital.

Bioorg Med Chem. 2008 Feb 15; 16(4): 1632-47
Yamawaki K, Nomura T, Yasukata T, Tanimoto N, Uotani K, Miwa H, Yamano Y, Takeda K, Nishitani Y

A novel series of 7beta-[2-(2-amino-5-chloro-thiazol-4-yl)-2(Z)-((S)-1-carboxyethoxyimino)acetamido]Cephalosporins bearing various pyridinium groups at the C-3' position were synthesized and their in vitro antibacterial activities against gram-negative pathogens including Pseudomonas aeruginosa and several gram-positive pathogens were evaluated. Among the Cephalosporins prepared, we found that a cephalosporin bearing the 2-amino-1-(3-methylamino-propyl)-1H-imidazo[4,5-b]pyridinium group at the C-3' position (8a) showed potent and well-balanced antibacterial activities against P. aeruginosa and other gram-negative pathogens including the strains which produce class C beta-lactamase and extended spectrum beta-lactamase (ESBL). Compound 8a also showed efficacious in vivo activity and high stability against AmpC beta-lactamase. These findings indicate that 2-aminoimidazopyridinium having an aminoalkyl group at the 1-position as a C-3' side chain is suitable for Cephalosporins bearing an aminochlorothiazolyl moiety and a carboxyethoxyimino moiety on the C-7 side chain.

Infection. 2007 Dec; 35(6): 414-20
Höffken G, Barth J, Rubinstein E, Beckmann H,

BACKGROUND: Empiric treatment of hospital-acquired pneumonia (HAP) should be focused on the suspected pathogens. We evaluated the efficacy and safety of moxifloxacin vs ceftriaxone in patients with HAP without risk of infections with Pseudomonas aeruginosa and other non-fermentative Gram-negative bacteria. PATIENTS AND METHODS: We performed a prospective, randomized, non-blind, multicentric and multinational study to compare the efficacy and safety of moxifloxacin 400 mg IV once daily followed by oral moxifloxacin 400 mg once daily to ceftriaxone 2 g IV once daily followed by oral cefuroxime axetil 500 mg twice daily to treat mild-to-moderate HAP in adult patients requiring initial parenteral therapy. The primary efficacy variable was clinical response 7-10 days after the end of a 7-14-day treatment period, secondary endpoints included clinical and bacteriologic response at different intervals for up to 31 days after treatment. The trial was terminated prematurely due to slow patient recruitment. RESULTS: A total of 161 subjects (87 men, 74 women) between 18 and 95 years of age were enrolled, 120 of whom were eligible for per protocol efficacy analyses (60 each in the moxifloxacin and the comparator groups). Clinical success rates were 87% for moxifloxacin and 83% for the comparator [95% CI (-9.77 to 15.96%)]. The results for secondary endpoints were comparable between groups. Both treatments were safe and well tolerated. CONCLUSION: Moxifloxacin IV/oral can be considered as a possible alternative for the antibiotic treatment of patients with mild-to-moderate nosocomial pneumonia without risk factors for highly resistant microorganisms.

J Fr Ophtalmol. 2007 Oct; 30(8): 807-13
Chédru-Legros V, Fines-Guyon M, Chérel A, Perdriel A, Albessard F, Debruyne D, Mouriaux F

INTRODUCTION: Fortified antibiotic ophthalmic solutions are regularly administered as an immediate treatment for bacterial keratitis. Fortified antibiotics used to be self-prepared by nurses. To solve this problem, pharmacy staff studied the stability of three 5% solutions of vancomycin, amikacin, and ceftazidime prepared in aseptic conditions from parenteral antibiotic solutions. MATERIAL AND METHODS: Solutions were frozen at -20 degrees C. Each solution were examined before storage and over a 75-day period. Ceftazidime and amikacin were diluted in 0.9% sodium chloride and vancomycin in 5% dextrose. Over a 75-day period, physical and pharmacological (absorbance spectra) properties and the sterility of each stock solution were studied. RESULTS: The pH of amikacin (6.51), ceftazidime (6.47), and vancomycin (3.77) remained stable during the 75-day period. Osmolarities also remained stable (367, 488, and 351 mOsm/L, respectively). There were no significant differences in the concentration, osmolarity, and pH of the three antibiotic solutions before storage and after 75 days of freezing. Over a 75-day period, the stability of amikacin, ceftazidime, and vancomycin remained constant; no contamination was detected before storage and after 75 days. CONCLUSION: Topical fortified antibiotic solutions can be stored for 75 days at -20 degrees C (15 days quarantine). After this time, these eye-drops should be stored at 4 degrees C and should be discarded after 3 days.

Int J Clin Pharmacol Ther. 2007 Oct; 45(10): 568-76
Dumpis U, Gulbinovic J, Struwe J, Lagergren A, Griskevicius L, Bergman U

OBJECTIVE: To identify inexpensive and simple quality parameters for the surveillance of antibiotic use in hospital settings. METHODS: A modified point-prevalence study was conducted in three university hospitals in Huddinge, Sweden, Riga, Latvia, and Vilnius, Lithuania. Each ward was visited once during May in the year 2002. All patients receiving antibiotics were identified and their medical records were reviewed by the authors according to the same protocol. Only data from corresponding departments were evaluated and compared. RESULTS: The prevalence of antibiotic use was 35%, 25% and 24% in Huddinge, Riga and Vilnius, respectively. Almost 2/3 of antibiotics were prescribed for treatment and 1/3 for either surgical or medical prophylaxis. parenteral administration was significantly more common in Riga and Vilnius than in Huddinge. The most commonly prescribed antibiotics were Cephalosporins and fluoroquinolones. Prescription of antibiotics for different diagnoses showed large variation between and within hospitals. The first or second generation Cephalosporins were prescribed in most cases of surgical prophylaxis. The duration of surgical prophylaxis exceeded one day in 57%, 63% and 87% of cases in Huddinge, Riga and Vilnius, respectively. All antibiotics in Huddinge, and all except five in Riga were supplied by the hospital pharmacy. Antibiotics bought by patients and donated made up 41% of prescribed antibiotics in Vilnius. CONCLUSION: This point-prevalence survey using a simple and inexpensive method for benchmarking demonstrated quantitative and qualitative differences in the use of antibiotics between three university hospitals in the Baltic region, differences that now calls for explanations to their rationality. We suggest that the choice of an antibiotic, rates of intravenously administered treatment and duration of surgical prophylaxis are examples of suitable indicators of rational antibiotic use within a hospital but that comparison of such rates between hospitals is less meaningful.

J Paediatr Child Health. 2008 Apr; 44(4): 214-8
Gouin S, Chevalier I, Gauthier M, Lamarre V

AIM: To assess the clinical outcome of patients with moderate to severe cellulitis managed at a paediatric day treatment centre (DTC). METHODS: Prospective observational study of all patients (3 months to 18 years) with a presumed diagnosis of moderate to severe cellulitis made in a university-affiliated paediatric emergency department (ED) (September 2003 to September 2005). Patients treated at the DTC were given ceftriaxone or clindamycin. RESULTS: During the study period, a presumed diagnosis of moderate to severe cellulitis was made in 224 patients in the ED. Ninety-two patients were treated at the DTC (41%). The cellulitis had a median width of 7.0 cm (range: 1.0-50.0 cm) and a median length of 6.5 cm (range: 1.0-40.0 cm). Blood cultures were performed in 95.7%; one was positive for Staphylococcus aureus. After a mean of 2.5 days of intravenous therapy (first injection in the ED and a mean of 1.5 days at the DTC), 73 patients (79.3%) were successfully discharged from the DTC and switched to an oral agent. For these patients no relapse occurred. Nineteen patients (20.7%) required inpatient admission for further therapy. No patient was diagnosed with necrotizing fasciitis in the course of therapy. Seventy-eight satisfaction questionnaires were handed in and revealed very good to excellent parental satisfaction with treatment at the DTC in 94.8%. CONCLUSION: Treatment with parenteral antibiotic at a DTC is a viable alternative to hospitalisation for moderate to severe cellulitis in children.

Eur J Ophthalmol. 2007 Sep-Oct; 17(5): 841-3
Brijlal Meena MK, Sharma P

PURPOSE: To report a case of epidural empyema, a rare complication of orbital cellulitis, underlining the importance of early diagnosis and appropriate therapy to avoid severe complications often associated with this disease. METHODS: The treatment was initiated with extended spectrum antibiotics such as third generation Cephalosporins along with aminoglycoside or metronidazole for anaerobes. RESULTS: The patient responded well and was asymptomatic after 15 days. Radiologic investigations (computed tomography/magnetic resonance imaging) should be done on an emergency basis. Treatment should be aggressive with parenteral use of extended spectrum antibiotics. The role of steroid is when proptosis is causing lagophthalmos with exposure keratitis and/or optic nerve compression. Judicious surgical intervention can be life saving in this emergency. Peribulbar antibiotic injection has no role in the therapy. CONCLUSIONS: The authors present a unique case of epidural empyema secondary to orbital cellulitis associated with an episode of epileptic seizure.

Bioorg Med Chem. 2007 Nov 1; 15(21): 6716-32
Yamawaki K, Nomura T, Yasukata T, Uotani K, Miwa H, Takeda K, Nishitani Y

A series of 7beta-[2-(2-aminothiazol-4-yl)-2-(Z)-(carboxymethoxyimino)acetamido]Cephalosporins bearing a 1-(substituted)-1H-pyrrolo[3,2-b]pyridinium group at C-3' position was synthesized and their in vitro antibacterial activities against Pseudomonas aeruginosa and other Gram-negative pathogens were evaluated. Among the Cephalosporins prepared, 7beta-[2-(2-amino-5-chlorothiazol-4yl)-2(Z)-((S)-1-carboxyethoxyimino)acetamido]Cephalosporins (42d) showed potent antibacterial activities against P. aeruginosa and other Gram-negative pathogens including the strains which produce class C beta-lactamase and extended spectrum beta-lactamase (ESBL). These results imply that both the Cl atom on the C-7 aminothiazole moiety and the alpha-substituent at the iminoether moiety are essential for the stability against beta-lactamase and the potent activity against Gram-negative bacteria including P. aeruginosa.

Postgrad Med J. 2007 Aug; 83(982): 552-5
Collini P, Beadsworth M, Anson J, Neal T, Burnham P, Deegan P, Beeching N, Miller A

OBJECTIVES: Appropriate assessment of community-acquired pneumonia (CAP) allows accurate severity scoring and hence optimal management, leading to reduced morbidity and mortality. British Thoracic Society (BTS) guidelines provide an appropriate score. Adherence to BTS guidelines was assessed in our medical assessment unit (MAU) in 2001/2 and again in 2005/6, 3 years after introducing an educational programme. METHODS: A retrospective case-note study, comparing diagnosis, documentation of severity, management and outcome of CAP during admission to MAU during 3 months of each winter in 2001/2 and 2005/6. RESULTS: In 2001/2, 65/165 patients were wrongly coded as CAP and 100 were included in the study. In 2005/6 43/130 were excluded and 87 enrolled. In 2005/6, 87% did not receive a severity score, a significant increase from 48% in 2001/2 (p<0.0001). parenteral antibiotics were given to 79% of patients in 2001/2 and 77% in 2005/6, and third generation Cephalosporins were given to 63% in 2001/2 and 54% in 2005/6 (p = NS). In 2001, 15 different antibiotic regimens were prescribed, increasing to 19 in 2005/6. CONCLUSIONS: Coding remains poor. Adherence to CAP management guidelines was poor and has significantly worsened. Educational programmes, alone, do not improve adherence. Restriction of antibiotic prescribing should be considered.

Am J Trop Med Hyg. 2007 Jul; 77(1): 118-20
Limmathurotsakul D, Chaowagul W, Wongsrikaew P, Narmwong A, Day NP, Peacock SJ

We describe three instructive cases of neurologic melioidosis that demonstrate the variable nature of clinical manifestations and disease pathology. The appropriate duration and choice of parenteral and oral antimicrobial therapy for neurologic melioidosis are also discussed.

BMJ. 2007 Aug 25; 335(7616): 386
Montini G, Toffolo A, Zucchetta P, Dall'Amico R, Gobber D, Calderan A, Maschio F, Pavanello L, Molinari PP, Scorrano D, Zanchetta S, Cassar W, Brisotto P, Corsini A, Sartori S, Da Dalt L, Murer L, Zacchello G

OBJECTIVE: To compare the efficacy of oral antibiotic treatment alone with treatment started parenterally and completed orally in children with a first episode of acute pyelonephritis. DESIGN: Multicentre, randomised controlled, open labelled, parallel group, non-inferiority trial. SETTING: 28 paediatric units in north east Italy. PARTICIPANTS: 502 children aged 1 month to <7 years with clinical pyelonephritis. INTERVENTION: Oral co-amoxiclav (50 mg/kg/day in three doses for 10 days) or parenteral ceftriaxone (50 mg/kg/day in a single parenteral dose) for three days, followed by oral co-amoxiclav (50 mg/kg/day in three divided doses for seven days). Main outcomes measures Primary outcome was the rate of renal scarring. Secondary measures of efficacy were time to defervescence (<37 degrees C), reduction in inflammatory indices, and percentage with sterile urine after 72 hours. An exploratory subgroup analysis was conducted in the children in whom pyelonephritis was confirmed by dimercaptosuccinic acid (DMSA) scintigraphy within 10 days after study entry. RESULTS: Intention to treat analysis showed no significant differences between oral (n=244) and parenteral (n=258) treatment, both in the primary outcome (scarring scintigraphy at 12 months 27/197 (13.7%) v 36/203 (17.7%), difference in risk -4%, 95% confidence interval -11.1% to 3.1%) and secondary outcomes (time to defervescence 36.9 hours (SD 19.7) v 34.3 hours (SD 20), mean difference 2.6 (-0.9 to 6.0); white cell count 9.8x10(9)/l (SD 3.5) v 9.5x10(9)/l (SD 3.1), mean difference 0.3 (-0.3 to 0.9); percentage with sterile urine 185/186 v 203/204, risk difference -0.05% (-1.5% to 1.4%)). Similar results were found in the subgroup of 278 children with confirmed acute pyelonephritis on scintigraphy at study entry. CONCLUSIONS: Treatment with oral antibiotics is as effective as parenteral then oral treatment in the management of the first episode of clinical pyelonephritis in children. TRIAL REGISTRATION: Clinical Trials NCT00161330 [ClinicalTrials.gov].