Bezzio, S.

Castagnola, E.

Caviglia, I.

Chiapello, N.

Fagioli, F.

Giacchino, M.

Moroni, C.

Saracco, P.

English

Institutional Research Information System University of Turin

15. Hawkins JM, Craig JM, Secker-Walker LM, et al. Ewing’s sarcomat(11;22) in a case of acute nonlymphocytic leukemia. Cancer GenetCytogenet 1991;55:157–162.16. Rosoff PM, Hatcher S, West DC. Biphenotypic sarcoma withcharacteristics of both a Ewing’s Sarcoma and a DesmoplasticSmall Round Cell Tumor. Med Pediatr Oncol 2000;34:407–412.17. Maitra A, Weinberg AG, Schneider N, et al. Detection of t:11;22)(q24;q12) translocation and EWS-FLI1 fusion transcript in a caseof solid pseudopapillary tumor of the pancreas. Pediatr Dev Pathol2000;3:603–605.18. Colpi GM, Contalbi GF, Nerva F, et al. Testicular functionfollowing chemo-radiotherapy. Eur J Obstet Gynecol Reprod Biol2004;113:S2–S6.19. Cicognani A, Pasini A, Pession A, et al. Gonadal function andpubertal development after treatment of a childhood malignancy.J Pediatr Endocrinol Metab 2003;16:321–326.20. Kenney LB, LauferMR, Grant FD, et al. High risk of infertility andlong term gonadal damage in males treated with high dosecyclophosphamide for sarcoma during childhood. Cancer 2001;91:613–621.Continuous Antibiotic Infusion for Salvage Therapy ofPartially Implanted Central Venous Catheter TunnelInfections Due to StaphylococciM. Giacchino, MD,*1 S. Bezzio, MD,1 N. Chiapello, MD,1 P. Saracco, MD,1 F. Fagioli, MD,1I. Caviglia, MD,2 C. Moroni, MD,2 and E. Castagnola, MD2INTRODUCTIONPartially implanted central venous catheters (CVCs) play anessential role in atraumatic, long-term venous access for chemo-therapy and for supportive care in patients with cancer orhematological diseases. Unfortunately, intravascular catheters arean important risk factor for local and systemic infections [1] amongwhich tunnel infection is an uncommon, but serious complication[2]. International guidelines advise therapy in tunnel infections withantibiotics and catheter removal [3]. However, this procedure mightnot always be feasible in patients in life-threatening clinicalconditions, or with limited vascular access sites such as in youngchildren with cancer, or with conditions that make catheterwithdrawal impossible or at least very difficult.Continuous infusion of beta-lactam antibiotics or vancomycinmight provide a constant and effective drug level, and represents anefficacious treatment of severe infections due to susceptiblepathogens [4,5]. Moreover, it has been demonstrated that in thetreatment of staphylococcal infections the continuous infusion ofvancomycin has equal efficacy and also a lower cost thanintermittent infusion [6]. Our report retrospectively evaluated theefficacy of continuous infusion of antibacterials with a time-dependent killing curve to treat partially implanted CVC tunnelinfections.PATIENTS AND METHODSWe retrospectively evaluated the episodes of tunnel infectiontreated with antibiotic continuous infusion from January 2000 toOctober 2004 at ‘‘Regina Margherita’’ Children’s Hospital, Turin,and ‘‘G. Gaslini’’ Children’s Hospital, Genoa, Italy. Tunnelinfection was defined by the presence of tenderness, erythema,and induration extended more than 2 cm beyond the CVC exit site,along the subcutaneous tract of the tunneled catheter, with a positiveexudate swab culture and/or concomitant bloodstream infection [3].Continuous antibiotic infusion consisted in the intra-catheteradministration of antibiotics by a 24-hr infusion, at a maximumdaily dose calculated according to patient weight (40 mg/kg/dayvancomycin, 100 mg/kg/day cefuroxime, and 320 mg/kg/daypiperacillin/tazobactam). The success of the procedure was definedby general and local improvement, negative cultures, and noinfectious relapse in the first month after the end of treatment.RESULTSDuring the study period, 13 episodes of CVC tunnel infectionswere treated with antibiotic continuous infusion. Table I summa-Tunnel infection is an uncommon but serious complicationobserved in patients with partially implanted central venouscatheters. International guidelines suggest that should includeantibiotics and catheter removal. A success rate of only 5–20%was reported without catheter removal. We treated 13 episodes oftunnel Gram-positive bacterial infection occurring in pediatricpatients with cancer or serious blood disorders with 24-hr intra-catheter antibiotic continuous infusion. This approach led to a 69%success rate. Continuous infusion might be an attractive option totreat tunnel Gram-positive bacterial infections when catheterremoval might not be feasible or advisable. Pediatr Blood Cancer2007;49:1010–1012.  2006 Wiley-Liss, Inc.Key words: central venous catheter; children; therapy; tunnel infection——————1Department of Pediatrics, ‘‘Regina Margherita’’ Children’s Hospital,Turin, Italy; 2Infectious Diseases Unit, Department of Hematology andOncology, ‘‘G. Gaslini’’ Children’s Hospital, Genoa, Italy*Correspondence to: Dr. M. Giacchino, Department of Hematology,Oncology, Immunology and Infectious Diseases, ‘‘Regina Margherita’’Children’s Hospital, P.za Polonia 94, 10129 Turin, Italy.E-mail: mareva.giacchino@unito.itReceived 19 October 2005; Accepted 14 March 2006 2006 Wiley-Liss, Inc.DOI 10.1002/pbc.208641010 Brief Reportsrizes patients’ age and underlying disease, presence of granulocy-topenia (absolute granulocyte count <1 109 cells/L) at time ofdiagnosis, etiology, treatment, and outcome of tunnel infection. Theinfections were due to Staphylococcus aureus (S. aureus) in eightcases and to coagulase-negative staphylococci in the other five. Tenepisodes were due to oxacillin-resistant strains and were treatedwith vancomycin. The remaining three cases, all due to oxacillin-susceptible bacteria, were treated with beta-lactam antibiotics.Continuous infusion with vancomycin or beta-lactams antibioticswas administered for amedian of 12 days (range 10–24) on the basisof clinical/microbiological response and recovery of absolutegranulocyte count. This treatment procedure was successful in ninecases (69%). In four patients the catheter was removed because ofthe persistence (three cases) or relapse (one case) of the localinfection (S. aureus in three cases and a coagulase-negativeStaphylococcus in the other). No significant differences were notedbetween the rate of failure with the use of vancomycin (3/10, 30%)and beta-lactam antibiotics (1/3, 33%). There were no deaths orother complications related to the infection. The treatment was welltolerated by all patients. In particular, creatinine serum levels,checked three times weekly, remained within the normal rangefor age.DISCUSSIONCatheter-related infections are often difficult to treat becausethey are caused by organisms embedded in a biofilm layer on thecatheter surface that allows the bacteria to survive despite hostdefenses. Moreover, antibiotics do not easily penetrate the biofilm.The bactericidal activity of vancomycin and beta-lactam antibioticsis time-dependent. The important determinant of their efficacy is theperiod when the serum concentration is above the minimalinhibitory concentration (MIC). Continuous intravenous adminis-tration produces a relatively constant concentration of antibioticwhich can be maintained above the MIC, thereby improving thepharmacodynamic properties [6], without evidences of increasedbacterial resistance [7]. Furthermore, it has been suggested that acontinuous exposure may be an effective alternative againstStaphylococcus strains with reduced susceptibility to vancomycin[7]. In our patients with tunnel Gram-positive bacterial infectionsthe use of continuous antibiotic infusion led to a 69% (9/13) successrate, while historical data report a success rate of 5–20% withmedical therapy without catheter removal [8]. Although theseresults may be biased because of their retrospective nature, theysuggest an improvement in outcome with this approach. Catheterremoval probably remains the ‘‘golden standard’’ to treat tunnelinfections in partially implanted CVCs [3]. However, our experi-ence suggests that continuous antibiotic infusion, for at least 10–14days, is effective, safe, and easy to administer. This approach shouldbe studied prospectively.ACKNOWLEDGMENTWe are grateful to Mr. AndrewMartin Garvey BA (Hons) LTCLfor editorial assistance.REFERENCES1. Viscoli C, Castagnola E. Factors predisposing cancer patients toinfection. Cancer Treat Res. 1995;79:1–30.2. Beekman SE, Henderson DK. Infections caused by percutaneousintravascular devices. In:Mandell GL,Bennett JE,DoolinR, editors.Principles and practice of infectious diseases. Philadelphia:Churchill Livingstone; 2005. pp 3347–3361.3. Mermel LA, Farr BM, Sherertz RJ, et al. Guidelines for themanagement of intravascular catheter-related infections. Clin InfectDis 2001;32:1249–1272.4. AmsdenGW, BallowCH, Bertino JS Jr., et al. Pharmacokinetics andpharmacodynamics of anti-infective agents. In: Mandell GL,Bennett JE, Doolin R, editors. Principles and practice of infectiousdiseases. Philadelphia: Churchill Livingstone; 2005. pp 271–280.5. Kasiakou SK, Sermaides GJ, Michalopoulos A, et al. Continuousversus intermittent intravenous administration of antibiotics: Ameta-analysis of randomised controlled trials. Lancet Infect Dis2005;5:581–589.Pediatr Blood Cancer DOI 10.1002/pbcTABLE I. Patients’ Characteristics, Etiology, Treatment, and Outcome of Tunnel Gram-Positive Bacterial InfectionsPt. Age Underlying disease HSCT Neutropenia BacteriaTherapyOutcomeDrug Days of treatment1 1 year Histiocytosis NO YES S. aureus Vancomycin 16 Failure2 3 years Neuroblastoma YES NO CNS Vancomycin 10 Failure3 2 years Aplastic anemia NO NO S. aureus Cefuroxime 18 Failure4 18 months Hemophilia NO NO S. aureus Vancomycin 10 Failure5 10 years ALL YES NO S. aureus Piperacillin/tazobactam 11 Success6 2 months Neuroblastoma NO NO S. aureus Cefuroxime 12 Success7 14 years Ewing sarcoma NO NO S. epidermidis Vancomycin 12 Success8 6 years AML YES YES S. hominis Vancomycin 24 Success9 3 years ALL NO NO S. aureus Vancomycin 12 Success10 4 years ALL NO NO CNS Vancomycin 11 Success11 14 years NHL YES YES S. aureus Vancomycin 14 Success12 7 years Neuroblastoma NO NO S. epidermidis Vancomycin 14 Success13 2 months RMS NO NO S. aureus Vancomycin 14 SuccessHSCT, hematopoietic stem cell transplant; ALL, acute lymphoblastic leukemia; AML, acute myeloblastic leukemia; NHL, non-Hodgkin’slymphoma; RMS, rhabdomyosarcoma; CNS, coagulase-negative staphylococci.Brief Reports 10116. Dalle JH, Gnansounou M, Husson MO, et al. Continuous infusion ofceftazidime in the empiric treatment of febrile neutropenic childrenwith cancer. J Pediatr Hematol Oncol 2002;24:714–716.7. Wysocki M, Delatour F, Faurisson F, et al. Continous versusintermittent infusion of vancomycin in severe staphylococcalinfections: Prospective multicenter randomized study. AntimicrobAgents Chemoter 2001;45:2460–2467.8. Fatkenheuer G, Buchheidt O, Cornely OA, et al. Central venouscatheter (CVC)-related infections in neutropenic patients. AnnHematol 2003;82:S149–S157.Clinical Appearance of Neuroblastoma 10 Years After ScreeningReinhold Kerbl, MD,1* Christian E. Urban, MD,1 Heinz Zotter, MD,1 Herwig Lackner, MD,1Petra Sovinz, MD,1 and Peter F. Ambros, PhD2INTRODUCTIONNeuroblastoma is the most common solid tumor in childhood,affecting 1 out of 6,000 children [1]. Despite new and developingtreatment options, the prognosis of advanced disease remains verypoor [2,3]. In order to detect neuroblastoma at earlier disease stages,nationwide urinary mass screening was introduced in Japan in 1985with the aim to detect neuroblastomas in a subclinical stage and thusto improve the prognosis [4]. Encouraging results concerningsurvival rate [5] prompted other countries or regions to introducesimilar screening programs [6]. In Austria, screening was introduc-ed in 1991 and continued until 2003 [7]. Infants (439,128) werescreened and 62 neuroblastomas were detected by screening. Sincethe early nineties, there was, however, increased concern thatscreening might increase neuroblastoma incidence without reduc-ing disease related mortality [8,9]. Finally, two large-scale con-trolled trials confirmed this assumption [10,11]. As a consequence,worldwide screening programs and studies were discontinued evenin Japan [12]. The aimof this studywas to evaluate the further coursein previous screening-positive cases classified as ‘false-positive’ topossibly detect any late presentations of neuroblastoma.METHODSA follow-up study was performed of 30 children previouslyclassified as ‘false-positive’ by neuroblastoma mass screening.Three-step evaluation consisted of analysis of the records of thenational neuroblastoma registry, data analysis of the screeningcenter which performed all catecholamine analyses for Austriasince 1990, and personal information provided by parents. For thispurpose, parents of previously screening-positive children werecontacted by phone and 27/30 cases were evaluable in this way.RESULTSMedian follow-up time was 113 months. In 26 patients, urinecatecholamines returned to normal within 6 months; none of thesepatients developed neuroblastoma in the further course. Fourchildren had elevated urine catecholamines for more than 6months.Characteristics of these cases are shown in Table I.A thorough clinical examination, including blood cell count,serum analysis, ultrasound, MIBG and CT scan, was performed forall four children; no visible tumor was detected. In two childrenwithout any clinical or other lab abnormalities, urine catechol-amines returned to normal 16 and 45months after the first screeningtest, respectively.In one female patient, moderate signs of dysmorphia wereobserved (discrete muscle hypotonia, discrete hyperpigmentation,strabismus, brittle hair, growth retardation, deep husky voice).However, chromosomal analysis and endocrinological tests, as wellas screening for inborn metabolic disorders, were all normal. Infollow-up, celiac disease was diagnosed in this patient. Despitegluten restriction, urine catecholamines (mostly dopamine) con-tinued to be elevated, and at a follow-up time of 113months, are stillclearly above normal. There is, however, no hint of neuroblastoma.In one case a neuroblastoma was diagnosed almost 10 years afterthe first positive screening result, and a further description isprovided for this patient.CASE REPORTIn February 1994, at the age of 8months, the female infant testedpositive for urinary mass screening. Two other urine samples wereA follow-up study was performed for children with previousrepeated positive results by neuroblastoma mass screening andnegative clinical results (30 out of 439,128 children screened inAustria between 1991 and 2003, median follow-up 113 months).Four children had continuously elevated urine catecholamines formore than 6 months. One of these patients was diagnosed with pelvicneuroblastoma andmultiple metastases 10 years after the first positivescreening result. In the light of a ‘wait and see’ strategy for localizedneuroblastomas, our observation suggests that these patients shouldbe further observed even after normalization of urine catechol-amines. Pediatr Blood Cancer 2007;49:1012–1014. 2006 Wiley-Liss, Inc.Key words: late presentation; mass screening; neuroblastoma——————1Department of Pediatrics and Adolescent Medicine, MedicalUniversity Graz, Graz, Austria; 2CCRI, Children’s Cancer ResearchInstitute, Vienna, AustriaGrant sponsor: Styrian Government; Grant sponsor: Styrian Children’sCancer Fund; Grant sponsor: Children’s Cancer Research Institute,Vienna (CCRI).*Correspondence to: Reinhold Kerbl, Department of Pediatrics andAdolescent Medicine, Medical University Graz, Auenbruggerplatz 30,A-8036 Graz, Austria. E-mail: reinhold.kerbl@meduni-graz.atReceived 20 October 2005; Accepted 8 February 2006 2006 Wiley-Liss, Inc.DOI 10.1002/pbc.208281012 Brief Reports

Continuous antibiotic infusion for salvage therapy of partially implanted central venous catheter tunnel infections due to staphylococci

https://iris.unito.it/bitstream/2318/1690825/2/pbc.20864.pdf

Continuous antibiotic infusion for salvage therapy of partially implanted central venous catheter tunnel infections due to staphylococci

Abstract

Similar works

Full text

Available Versions

Institutional Research Information System University of Turin