Should We Screen Patients for Extended‐Spectrum β‐Lactamase–Producing Enterobacteriaceae in...

Should We Screen Patients for Extended‐Spectrum β‐Lactamase–Producing Enterobacteriaceaein Intensive Care Units? • Author(s): Elisabeth Meyer, MD; Annerose Serr, MD; Christian Schneider, MD; Stefan Utzolino,MD; Winfried V. Kern, MD, PhD; Regina Scholz; Markus Dettenkofer, MD, PhDSource: Infection Control and Hospital Epidemiology, Vol. 30, No. 1 (January 2009), pp. 103-105Published by: The University of Chicago Press on behalf of The Society for Healthcare Epidemiologyof AmericaStable URL: http://www.jstor.org/stable/10.1086/592702 .

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infection control and hospital epidemiology january 2009, vol. 30, no. 1

l e t t e r s t o t h e e d i t o r

table. Data Collected During the Admission Screening of Patients for Extended-Spectrum b-Lacta-mase–Producing Enterobacteriaceae in 4 Intensive Care Units (ICUs) at the University Medical CenterFreiburg, Germany, 2007

ICU Period

Proportion (%) of patients

Screened, with colonizationor infection detected

for the first time

Admitted, whowere infectedor colonized

With rectal colonization,who subsequently

developed infection

A Oct 1–Dec 31 3/48 (6.3) 4/137 (2.9) 3/3 (100)B Oct 1–Dec 31 6/67 (9.0) 14/230 (6.1) 1/8 (12.5)C Aug 15–Dec 31 14/463 (3.0) 25/1,057 (2.4) 5/15 (33.3)D Oct 1–Dec 31 6/177 (3.4) 9/250 (3.6) 0/9 (0)

Total 29/755 (3.8) 52/1,674 (3.1) 9/35 (25.7)

Prevention of Ventilator-AssociatedPneumonia by Use of Oral Chlorhexidine

To the Editor—We read with interest the article by Tantiponget al.1 on the use of oral decontamination with 2% chlor-hexidine solution for the prevention of ventilator-associatedpneumonia (VAP). We believe that their study has some im-portant limitations and that the authors’ conclusion that oralchlorhexidine is an effective and safe method for VAP pre-vention is not supported by the results.

In their study, some patients received ventilation for lessthan 48 hours, the population was not homogeneous, andthe randomization procedure was not adequate. The meanduration of mechanical ventilation was approximately 5 days,but only 43% of patients in the test group and 50% of patientsin the control group received ventilation for more than 48hours, a period that, if not completed, is usually consideredan exclusion criterion in the majority of trials on VAP pre-vention. Approximately 60% of patients admitted to theirstudy were adults who received ventilation in intensive careunits (ICUs) (mainly surgical ICUs), whereas 40% receivedventilation in general medical wards. Although the meanAcute Physiology and Chronic Health Evaluation II score wasnot significantly different among the 2 arms, it is highly likelythat patients who received ventilation in general medicalwards were in less “critical” condition than those treated inICUs. Moreover, the care of a patient who receives ventilationmay be different in the general ward than in the ICU, allwards did not change their regular protocols, parenteral an-tibiotic policy was not reported, semirecumbency was main-tained only “if possible,” and the degree of semirecumbencywas not assessed. Therefore, the study results seem to not begeneralizable to the high-risk ICU population. Finally, ran-domization according to patient sex is not an adequatemethod of randomization, the study was not blinded, and it

is not clear whether consecutive patients were enrolled. Allthese issues may have influenced the results and should beacknowledged by the authors.

The authors’ claim that oral decontamination with 2%chlorhexidine solution is an effective method for reducingVAP is not supported by the results and may be misleadingfor the reader. Although use of chlorhexidine reduced therisk of VAP by approximately 55% in the overall populationand among patients who received mechanical ventilation formore than 2 days, this reduction was not statistically signifi-cant, because both relative-risk (RR) calculations had large95% confidence intervals (CIs) (RR, 0.43 [95% CI, 0.16–1.17]for study patients who received mechanical ventilation andoral decontamination and RR, 0.45 [95% CI, 0.16–1.23] forpatients who received mechanical ventilation for more than2 days). The study showed a significant, albeit borderline( ), reduction in the number of episodes of pneu-P p .04monia per 1,000 ventilator-days, but this reduction was notstatistically significant ( ) when the authors evaluatedP p .06only patients who received mechanical ventilation for morethan 48 hours, which is an acceptable period for the diagnosisof VAP.

The authors stated that all VAP cases were due to gram-negative bacilli, but they were unable to specify the type ofmicroorganism. Many different microorganisms are includedin the category of gram-negative bacilli, which may have avariety of associated morbidity and mortality. Haemophilusinfluenzae, a gram-negative bacillus that belongs to the “nor-mal” oropharyngeal flora, is readily cleared by parenteral an-tibiotics and usually causes VAP soon after the initiation ofmechanical ventilation.2 Aerobic gram-negative bacilli of the“abnormal flora,” such as Pseudomonas, Klebsiella, Serratia,Enterobacter, Citrobacter, Proteus, and Acinetobacter species,may cause VAP after 1 week in the ICU and are associatedwith increased morbidity and mortality.3

The authors assessed the safety of oral decontaminationwith 2% chlorhexidine solution by evaluating the irritation



102 infection control and hospital epidemiology january 2009, vol. 30, no. 1

of the oropharyngeal mucosa. Again, they stated that themethod was safe, ignoring their own findings of a significantincrease in mild mucosa irritation in the test group.

Finally, the authors performed a meta-analysis, which in-cluded their study and that of Koeman et al.,4 that demon-strated a significant reduction in the rate of VAP associatedwith the use of chlorhexidine (pooled RR, 0.53 [95% CI, 0.31–0.90]). Four meta-analyses of randomized, controlled trialsof oral antiseptics have been published.5-8 Two of these meta-analyses failed to show any significant reduction in pneu-monia rates,5,6 and the other 2 revealed a significantreduction.7,8 However, these positive results should be inter-preted with caution for the following reasons. (1) More thantwo-thirds of patients included in these meta-analyses werecardiac surgery patients who received a very short period ofmechanical ventilation and therefore had a low risk for de-veloping VAP; those studies included reported the incidenceof nosocomial pneumonia, not that of VAP9 (eg, “most ofthe patients received only 2 doses of the oral rinse agentsbecause extubation routinely occurred within 4–8 hours aftersurgery” [p 2468]). (2) In studies including surgical patients,perioperative prophylaxis with parenteral antibiotics was al-ways given. (3) Not all consecutive patients were enrolled insome studies that focused on dental plaque instead of theoropharynx, which excluded edentulous patients. (4) Therewere different definitions of respiratory tract infection, be-cause some studies reported the incidence of lower respiratorytract infections, including tracheobronchitis, whereas otherstudies included only incidences of VAP. (5) Oral chlorhex-idine was administered using multiple application forms (ie,solution, spray, gel, and paste) and a variety of concentrations(0.12%–2%), dosages (1–4 doses per day), and durations (ie,once, for 10 days, or until extubation). A recent meta-analysisconcluded that use of oral chlorhexidine might be effectivein preventing lower respiratory tract infections in patientsreceiving mechanical ventilation for up to 48 hours, althoughits impact in preventing late-onset VAP requires further re-search.8 Remarkably, none of those meta-analyses, or thestudy by Tantipong et al.1 demonstrated any impact onmortality.

acknowledgments

Potential conflicts of interest. All authors report no conflicts of interest rel-evant to this study.

Luciano Silvestri, MD;Hendrick K. F. van Saene, MD, PhD, FRCPath;

Marco Milanese, MD; Eraldo Zei, RN; Miranda Blazic, RN

From the Department of Emergency, Unit of Anesthesia and IntensiveCare Presidio Ospedaliero, Gorizia, Italy (L.S., M.M., E.Z., M.B.); and theDepartment of Medical Microbiology, University of Liverpool, Liverpool,United Kingdom (H.K.F.v.S.).

Address reprint requests to Luciano Silvestri, MD, Department ofEmergency, Unit of Anesthesia and Intensive Care, Presidio Ospedaliero diGorizia, Via Vittorio Veneto 171, 34170 Gorizia, Italy ([email protected]).

Infect Control Hosp Epidemiol 2008; 30:101-102� 2008 by The Society for Healthcare Epidemiology of America. All rightsreserved. 0899-823X/2009/3001-0024$15.00. DOI: 10.1086/591742

references

1. Tantipong H, Morkchareonpong C, Jaiyindee S, Thamlikitkul V. Ran-domized controlled trial and meta-analysis of oral decontamination with2% chlorhexidine solution for the prevention of ventilator-associatedpneumonia. Infect Control Hosp Epidemiol 2008; 29:131–136.

2. Rello J, Ricart M, Ausina V, Net A, Prats G. Pneumonia due to Hae-mophilus influenzae among mechanically ventilated patients: incidence,outcome, and risk factors. Chest 1992; 102:1562–1565.

3. Park DR. The microbiology of ventilator-associated pneumonia. RespirCare 2005; 50:742–763.

4. Koeman M, van der Ven AJ, Hak E, et al. Oral decontamination withchlorhexidine reduces the incidence of ventilator-associated pneumonia.Am J Respir Crit Care Med 2006; 173:1348–1355.

5. Pineda LA, Saliba G, El Solh AA. Effect of oral decontamination withchlorhexidine on the incidence of nosocomial pneumonia: a meta-analysis.Crit Care 2006; 10:R35.

6. Chlebicki MP, Safdar N. Topical chlorhexidine for prevention of ventilator-associated pneumonia: a meta-analysis. Crit Care Med 2007; 35:595–602.

7. Chan EY, Ruest A, Meade MO, Cook DJ. Oral decontaminations froprevention of pneumonia in mechanically ventilated adults: systematicreview and meta-analysis. BMJ 2007; 334:889–893.

8. Kola A, Gastmeier P. Efficacy of oral chlorhexidine in preventing lowerrespiratory tract infections: meta-analysis of randomized controlled trials.J Hosp Infect 2007; 66:207–216.

9. Silvestri L, van Saene JJM, van Saene HKF, Weir I. Topical chlorhexidineand ventilator-associated pneumonia. Crit Care Med 2007; 35:2468.

Reply to Silvestri et al.

To the Editor—We welcome the comments of Silvestri et al.1

regarding our article2 on the effectiveness of chlorhexidinefor the prevention of ventilator-associated pneumonia (VAP).We offer the responses.

We included all patients who underwent mechanical ven-tilation, because we wanted to determine the effectiveness of2% chlorhexidine solution for the prevention of VAP in allpatients who underwent mechanical ventilation, not only thepatients who underwent it for more than 48 hours. Therefore,our study results should be more generalizable than the resultsof a study that included only the patients who received me-chanical ventilation for more than 48 hours.

The patients who received mechanical ventilation in generalmedical wards were not in less critical condition than thosewho received mechanical ventilation in intensive care units.Many critically ill patients had to stay in general medical wardsbecause intensive care units had limited capacity, and beds inintensive care units were not available for all patients whoreceived mechanical ventilation in developing countries. There-fore, the study population should have been homogeneous.

Furthermore, we were unable to perform a double blindstudy, because the odor of chlorhexidine is very distinctive



letters to the editor 103

and could not be imitated. We tried to avoid biases by blind-ing the observer who determined whether each patient de-veloped VAP.

The fact that the incidence of VAP in the interventiongroup was not statistically significantly different from that inthe control group was most likely the result of an inadequatesample size. Therefore, we conducted a meta-analysis andfound that 2% chlorhexidine was effective for the preventionof VAP. Moreover, we observed that the rate of VAP (meannumber of cases per 1,000 ventilation-days) in the interven-tion group was significantly less than that in the controlgroup. We focused attention on the clinical importance ofthe study results (the 50% reduction in the rate of VAP),rather than on the P values (the incidence of VAP was 4.9%in the chlorhexidine and 11.4% in the normal saline group;

). The causative agents of VAP in all study patientsP p .08were mainly Pseudomonas aeruginosa, Acinetobacter bauman-nii, and Klebsiella pneumoniae.

We were concerned about the adverse effects of chlorhex-idine, such as irritation of oral mucosa, as was indicated inour article.2 We mentioned the factors that might increasethe risk of irritation of oral mucosa and warned the healthcareworkers who wanted to implement this intervention for theirpatients. However, we considered that the benefit of VAPprevention outweighed the risk of adverse effects.

We believe that the results of the meta-analysis were valid,because we included only the studies that used 2% chlor-hexidine for patients who received mechanical ventilation.The meta-analyses mentioned by Silvestri et al.1 includedstudies that used less-concentrated chlorhexidine and in-cluded a different population. Although 2% chlorhexidinesolution did not significantly decrease mortality among pa-tients who received mechanical ventilation, our interventionwas very cost-effective.

acknowledgments

Potential conflicts of interest. All authors report no conflicts of interest rel-evant to this article.

Visanu Thamlikitkul, MD; Hutsaya Tantipong, MD;Chantana Morkchareonpong, MD; Songyod Jaiyindee, MD

From the Department of Medicine, Faculty of Medicine Siriraj Hospital,Mahidol University, Bangkok, Thailand (all authors).

Address reprint requests to Visanu Thamlikitkul, MD, Department ofMedicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok10700, Thailand ([email protected]).Infect Control Hosp Epidemiol 2009; 30:102-103� 2008 by The Society for Healthcare Epidemiology of America. All rightsreserved. 0899-823X/2009/3001-0025$15.00. DOI: 10.1086/595859

references

1. Silvestri L, van Saene HKF, Milanese M, Zei E, Blazic M. Prevention ofventilator-associated pneumonia by use of oral chlorexidine. Infect ControlHosp Epidemiol 2008; 29:101–102 (in this issue).

2. Tantipong H, Morkchareonpong C, Jaiyindee S, Thamlikitkul V. Ran-domized controlled trial and meta-analysis of oral decontamination with2% chlorhexidine solution for the prevention of ventilator-associatedpneumonia. Infect Control Hosp Epidemiol 2008; 29:131-6.

Should We Screen Patients for Extended-Spectrum b-Lactamase–ProducingEnterobacteriaceae in Intensive Care Units?

To the Editor—There have been an increasing number ofreports worldwide demonstrating that Enterobacteriaceae, es-pecially Escherichia coli and Klebsiella pneumoniae, have fre-quently become producers of extended-spectrum b-lacta-mases (ESBLs).1-3 Such ESBL-producing organisms areresistant to broad-spectrum penicillins and many cephalo-sporins. In addition, these organisms frequently are resistantto other agents (eg, fluoroquinolones) and can transmit theirresistance genes by way of plasmids.4 Unlike for other path-ogens (eg, methicillin-resistant Staphylococcus aureus[MRSA]) that are difficult to treat, the optimal strategy tocombat the spread of ESBL-positive organisms is unknown.Screening patients who are at risk could be beneficial, but anoptimal screening method has not been found, and screeningfor such ESBL-producing organisms has been limited. In2006, the University Medical Center Freiburg faced a dramaticincrease in the number of patients with infections due toESBL-positive Enterobacteriaceae. Therefore, we introducedadmission screening in 4 intensive care units (ICUs) to de-termine the prevalence of ESBL-positive patients in thesehigh-risk areas.

The University Medical Center Freiburg is a 1,600-bed uni-versity hospital with all of the clinical specialities. Approxi-mately 60,000 patients are admitted each year, accounting fora total of 440,000 patient-days.

In addition to standard precautions, contact precautionsare generally recommended only for patients infected withESBL-positive bacteria at the University Medical Center Frei-burg. These contact precautions include housing the patientin a single room or cohorting the patient with other infectedor colonized patients, the wearing of gloves and gowns byhealthcare workers, and the performance of rectal screeningof roommates for ESBL producers. During the study period(August through December 2007), 4 surgical ICUs (referredto as ICUs A, B, C, and D) were instructed to screen patientsfor infection due to ESBL-positive Enterobacteriaceae bymeans of culture of rectal samples. Mainly patients who haveundergone a solid-organ transplant are admitted to ICU A,those who have undergone cardiovascular surgery are ad-mitted to ICU B, those who have undergone visceral or or-thopaedic surgery are admitted to ICU C, and trauma patientsare admitted to ICU D.

Cultures were performed on a chromogenic medium for




the screening of ESBL-positive Enterobacteriaceae (chromIDESBL; bioMerieux) for all submitted rectal swab samples. Thischromogenic agar contains a mixture of antibiotics, includingcefpodoxim, and allows for the discrimination of differentspecies or genera of Enterobacteriaceae on the basis of colonycoloration. Additionally, cultures used as growth controlswere performed on Columbia blood agar plates (Becton-Dickinson). Colonies that we thought were producers of ESBLwere confirmed by the use of a commercial combination-disk method (ESBL Set; MAST Diagnostics) that containedcefotaxim, ceftazidim, and cefpodoxim with or without cla-vulanate and by the use of a double-disk synergy test thatcontained ceftriaxone and amoxicillin-clavulanate.5

Clinical samples other than rectal swab samples were cul-tured, and antibiotic resistance testing was performed ac-cording to standard laboratory procedures. According to thecriteria of the Clinical and Laboratory Standards Institute, ifreduced susceptibility to cephalosporins was detected in En-terobacteriaceae, the isolates were checked for production ofESBL, as described above.

Admission screening was performed for 755 (45%) of the1,674 newly admitted patients to the 4 ICUs during the studyperiod (Table). The majority of the patients who were notscreened were expected to stay in the ICU for only a fewhours. The rate of carriage of ESBL carriers detected by ad-mission screening ranged from 3.0% to 9.0% of patients perICU (Table). Overall, 35 (5%) of the 755 patients screenedhad rectal colonization, but only 6 (17%) of the 35 patientswere already known to carry ESBL-producing organisms. Ifthe isolation of ESBL-producing organisms from clinical cul-tures is included in the analysis, then 2.4%–6.1% of patientsper ICU were found to be positive for ESBL-producing path-ogens; 52 (7%) of the 755 patients screened were infected orcolonized with ESBL-producing pathogens, and 9 (25.7%) ofthe 35 patients with rectal colonization developed a subse-quent infection (ie, 5 developed a urinary tract infection, 2developed a surgical site infection, 1 developed pneumonia,and 1 developed pleural empyema).

Guidelines for the care of patients infected with ESBL-producing bacteria vary and do not necessarily includescreening for ESBL-producing organisms. However, there isbroad evidence to suggest that, with respect to MRSA, thescreening and identification of patients at risk are crucial forinfection control.6

We analyzed the situation in 4 ICUs in a German tertiarycare hospital and were surprised to find a mean ESBL carriagerate of 5% during admission screening, a rate similar to whathas been reported recently from the United States.1 In thatlatter, larger study from the United States by Reddy et al.1

involving approximately 17,000 patients from 4 ICUs, a pro-gressive increase in the incidence of ESBL-producing Enter-obacteriaceae colonization was reported during the 6-yearperiod of the study. The mean rate reached 3% in 2005,ranging from 7% in the medical ICU to 4% in the surgicalICU. Data from Israel and Saudi Arabia indicate colonizationrates in excess of 10% and even 26%.2,3

Rectal colonization is a known risk factor for infection dueto ESBL-producing Enterobacteriaceae.2 Reddy et al.1 re-ported that 35 (8.5%) of 413 patients colonized with ESBL-producing Enterobacteriaceae developed a subsequent blood-stream infection.1 In our study, every fourth colonized patientsuffered from an infection caused by an ESBL-producing or-ganism during the course of their hospital stay. In 2007 atour hospital, the hospital-wide burden (ie, the number ofcases per 1,000 patient-days) of infections due to ESBL-pos-itive bacteria was twice as high as that of MRSA infections(0.3 vs 0.15 cases per 1,000 patient-days; data not shown).

In consideration of the fact that the burden of infectionsdue to ESBL-producing bacteria is high and continues to riseand that the risk of developing a subsequent infection dueto an ESBL-producing organism is considerable, we advocateintroducing admission screening for high-risk patients withsevere underlying disease (eg, for patients who have had se-vere trauma, who have undergone major surgery or a trans-plant, and/or who have been admitted to a hematology unit),because these are the types of patients who frequently developnosocomial infection and in whom early and adequate em-pirical antibiotic treatment is vital. This is in contrast toMRSA screening; as long as the exact reservoir and prevalentmodes of transmission remain unclear, it might not be helpfulto restrict admission screening to only high-risk patients who,for example, have invasive devices in place, are on dialysis,or have chronic wounds. With such a program, it should bepossible to provide data relevant for cost-benefit analyses.

acknowledgments


Elisabeth Meyer, MD; Annerose Serr, MD;Christian Schneider, MD; Stefan Utzolino, MD;

Winfried V. Kern, MD, PhD; Regina Scholz;Markus Dettenkofer, MD, PhD

From the Institute of Environmental Health Sciences (E.M., R.S., M.D.),the Department for Medical Microbiology and Hygiene (A.S., C.S.), theDepartment of General and Visceral Surgery (S.U.), and the Center forInfectious Diseases and Travel Medicine (W.K.), University Medical CenterFreiburg, Freiburg, Germany.

Address reprint requests to Elisabeth Meyer, MD, Institute of Hygieneand Environmental Medicine, Charite University Medicine Berlin,Hindenburgdamm 12, 12203 Berlin, Germany ([email protected]).Infect Control Hosp Epidemiol 2009; 30:103-105� 2008 by The Society for Healthcare Epidemiology of America. All rightsreserved. 0899-823X/2009/3001-0026$15.00. DOI: 10.1086/592702

references

1. Reddy P, Malczynski M, Obias A, et al. Screening for extended-spectrumb-lactamase–producing Enterobacteriaceae among high-risk patients andrates of subsequent bacteremia. Clin Infect Dis 2007; 45:846-852.

2. Ben-Ami R, Schwaber MJ, Navon-Venezia S, et al. Influx of extended-



letters to the editor 105

spectrum b-lactamase–producing Enterobacteriaceae into the hospital.Clin Infect Dis 2006; 42:925-934.

3. Kader AA, Kumar A, Kamath KA. Fecal carriage of extended-spectrumb-lactamase–producing Escherichia coli and Klebsiella pneumoniae in pa-tients and asymptomatic healthy individuals. Infect Control Hosp Epidemiol2007; 28:1114-1116.

4. Pitout JD, Laupland KB. Extended-spectrum b-lactamase-producing En-terobacteriaceae: an emerging public-health concern. Lancet Infect Dis2008; 8:159-166.

5. Jarlier V, Nicolas MH, Fournier G, Philippon A. Extended broad-spectrumb-lactamases conferring transferable resistance to newer b-lactam agentsin Enterobacteriaceae: hospital prevalence and susceptibility patterns. RevInfect Dis 1988; 10:867-878.

6. Siegel JD, Rhinehart E, Jackson M, Chiarello L; Health Care InfectionControl Practices Advisory Committee. 2007 guideline for isolation pre-cautions: preventing transmission of infectious agents in health care set-tings. Am J Infect Control 2007; 35: S65-S164.

Infectious Complications AfterReimplantation of Bone Flapsin Patients Who UnderwentDecompressive Craniectomy

To the Editor—As a neurosurgical procedure, decompressivecraniectomy has been described as a therapeutic approach tointractable intracranial pressure—resulting from a traumaticbrain injury or brain edema of other etiology—and malignantmiddle cerebral artery infarction, as outlined in a number ofalgorithms for therapy.1 Some of the technical details of theprocedure, including the storage of removed bone flaps, aremostly based on institutional experience, and the infectiouscomplications associated with delayed cranioplastic repairhave not been routinely monitored.

A survey consisting of the following 5 questions was e-mailed to a representative convenience sample of 100 largeand small neurosurgical departments at university, teaching,and community hospitals in Germany: (1) How many de-compressive craniectomies were performed between 2004 and2006? (2) How many bone flaps were reimplanted between2004 and 2006? (3) How many infections (ie, clinical diag-nosis in a patient’s record) associated with bone-flap reim-plantation were observed between 2004 and 2006? (4) Howare bone flaps stored at your institution? (5) Is there a max-imal storage duration at your institution?

The medical insititutions from which the quality assurancedata were collected and recorded remained anonymous; anyidentifiers of the institutions were destroyed after being en-tered into a spread sheet (Excel 2003; Microsoft DeutschlandGmbH), in compliance with German federal data protectionlaws. Specific institutional review board authorization is notrequired by German law for this kind of research.

Only the data sets of 12 medical centers could be fullyanalyzed, because many institutions were not able to matchdecompressive craniectomies with their respective reimplan-

tation procedures or to provide infection rates; these insi-tutions had to be excluded. Therefore, the planned multipleregression analysis using JMP, version 5.1 (SAS), had to beabandoned because of the small number of medical centersincluded in our study.

In the 12 medical centers included in the study, 682 de-compressive craniectomies (range, 4–335 procedures permedical center) and 301 bone-flap reimplantation procedures(range, 2–137 procedures per medical center) had been per-formed. This represents a mean reimplantation rate of 44%(range, 37%–75%). Of the 301 bone-flap reimplantation pro-cedures, 22 were reported to have infectious complications(mean infection rate, 7.3%; range, 0%–11.7%). There was alarge variation in maximal storage times among the 12 med-ical centers: no restrictions, 1 month, 6 months, 12 months,24 months, and up to 5 years. The 12 medical centers’ practicepatterns for storage were also highly variable, including frozenstorage at �80�C ( ), �70�C ( ), �24�C ( ),n p 3 n p 3 n p 1and an unknown temperature ( ) and bone-flap im-n p 3plantation in the abdominal wall ( ). Bone flaps weren p 2pretreated with either Lavasept (BBraun AG) for 5 minutes( ) or Jodobac (Bode Chemie) for 30 minutes ( ),n p 1 n p 1or they were boiled in sterile normal saline for 20 minutesbefore freezing ( ). The infection rate in the medicaln p 1center with a storage temperature of �24�C was the highestat 11.7%; however, no valid statistical analysis could be per-formed because of the small number of medical centers inour study.

Decompressive craniectomy is reported to be a lifesavingrescue procedure for selected patients, although its definiteplace in algorithms for therapy for intractable intracranialpressure still needs to be determined.1 With the increasedutilization of this neurosurgical procedure, the questions ofhow to handle, store, and reimplant bone flaps harvested atinitial decompression and the infectious complications as-sociated with delayed cranioplasty become an important issuefor the long-term care of those often severely ill patients.

Our study was limited by the small number of completedata sets for analysis, which is one of the major drawbacksof surveys, and highlights the demand for prospective sur-veillance efforts. The infection rate that we calculated in ourstudy is in accordance with the rates found in the literature(ie, 2.1%–7.8% in larger case series).2,3 However, no commondefinitions for infectious complications after delayed cran-ioplasty are in place, which limits comparison. The storageprocedures described in the literature also differ from onemedical center to the next. For example, freezing techniquesinclude freezing at �35�C or �84�C without pretreatment,3

at �80�C after rinsing with neomycin,4 at �16�C after im-mersion in amikacin sulphate,5 and at �20�C in 100% ethanolsolution and autoclaving before reimplantation.6 Jho et al.2

described a technique that uses gas sterilization with ethyleneoxide for storing explanted skull bone at room temperature,and interest is growing in the intracorporeal storage of bonein the abdominal wall7 or in a subgaleal pocket,8 especiallyin regions of the world where extracorporeal storage is limited




because of problems with electricity and infrastructure. How-ever, with regard to graft survival and the rate of infectionafter reimplantation of bone flaps, the differences betweenintracorporeal and extracorporeal storage modalities need tobe determined before a final recommendation for the properstorage of bone flaps can be made. Also, the effects of thematerial used to fix the bone flap (eg, the use of a titaniumclamp system [Craniofix; BBraun AG] and plates [Leibinger])remain unclear.

In summary, our survey of 12 medical centers and ourreview of the literature reveal nonstandardized, highly vari-able protocols for the handling of bone flaps after decom-pressive craniectomy. With a mean infection rate of approx-imately 7%, a comprehensive approach to evaluating thesepractice patterns for the storage of bone flaps is warranted.

Ideally, a prospective, randomized trial would compare in-tracorporeal and extracorporeal storage techniques, but, giventhe large number of patients needed to reach sufficient power,this option seems unrealistic. Therefore, the development ofstandardized definitions of infections associated with delayedcranioplasty after decompressive craniectomy and the inclusionof these definitions as a marker in established surveillance sys-tems (eg, the National Nosocomial Infections Surveillance sys-tem9 and the Krankenhaus Infektions Surveillance System10)might be an alternative approach to evaluating current practicepatterns and might improve a patient’s outcome in the future.

acknowledgment


Sebastian Schulz-Stubner, MD; Rolf Rossaint, MD, PhD;Markus Dettenkofer, MD, PhD; Ruth Thiex, MD, PhD

From the Beratungszentrum fur Hygiene (S.S.-S.), the Institut furUmweltmedizin und Krankenhaushygiene der Albert-Ludwigs-Universi-tat Freiburg (M.D.), Freiburg, the Klinik fur Anasthesiologie amUniversitatsklinikum der Rheinisch-Westfalische Technische Hochschule

Aachen (R.R.), and the Neurochirurgische Klinik, UniversitatsklinikumAachen (R.T.), Aachen, Germany. (Present affiliation: Department ofNeurosurgery, Division of Endovascular Neurosurgery and InterventionalNeuroradiology, Brigham and Women’s Hospital, Harvard Medical School,Boston, Massachusetts [R.T.].)

Address reprint requests to Sebastian Schulz-Stubner, MD,Beratungszentrum fur Hygiene, Stuhlinger Str. 21, 79106 Freiburg im Breisgau0761-2026780, Germany ([email protected]).Infect Control Hosp Epidemiol 2009; 30:105-106� 2008 by The Society for Healthcare Epidemiology of America. All rightsreserved. 0899-823X/2009/3001-0027$15.00. DOI: 10.1086/592701

references

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