We present the case of a diabetic man who was successfully treated with ertapenem for over 4 months for severe infection of his foot ulcers. After initial unsuccessful treatment with empirical intravenous antibiotics, ertapenem was started on microbiology advice and led to a marked improvement in the soft-tissue infection. Ertapenem was continued for a total of 137 days under close clinical and biochemical monitoring and produced a complete resolution of the foot infection. This is the first documented case that we know of in which ertapenem has been safely used for this duration of time

Ahmad, Fareeduddin

Algudkar, Ashwin

Ellis, Gidon

Tindall, Hilary

English

PubMed

We present the case of a diabetic man who was successfully treated with ertapenem for over 4 months for severe infection of his foot ulcers. After initial unsuccessful treatment with empirical intravenous antibiotics, ertapenem was started on microbiology advice and led to a marked improvement in the soft-tissue infection. Ertapenem was continued for a total of 137 days under close clinical and biochemical monitoring and produced a complete resolution of the foot infection. This is the first documented case that we know of in which ertapenem has been safely used for this duration of time.</jats:p

Ashwin Algudkar

Gidon Ellis

Fareeduddin Ahmad

Hilary Tindall

Crossref

Hindawi Publishing CorporationCase Reports in MedicineVolume 2010, Article ID 149591, 4 pagesdoi:10.1155/2010/149591Case ReportProlonged Use of Ertapenem to Treat InfectedDiabetic Foot UlcersAshwin Algudkar, Gidon Ellis, Fareeduddin Ahmad, and Hilary TindallDepartment of Microbiology, North Middlesex Hospital, Stirling Way, Edmonton, London N18 1QX, UKCorrespondence should be addressed to Ashwin Algudkar, ashwin.algudkar@imperial.ac.ukReceived 24 July 2010; Revised 12 September 2010; Accepted 13 September 2010Academic Editor: Anthony W. ChowCopyright © 2010 Ashwin Algudkar et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.We present the case of a diabetic man who was successfully treated with ertapenem for over 4 months for severe infection of hisfoot ulcers. After initial unsuccessful treatment with empirical intravenous antibiotics, ertapenem was started on microbiologyadvice and led to a marked improvement in the soft-tissue infection. Ertapenem was continued for a total of 137 days under closeclinical and biochemical monitoring and produced a complete resolution of the foot infection. This is the first documented casethat we know of in which ertapenem has been safely used for this duration of time.1. IntroductionWe present the case of a diabetic man who was successfullytreated with ertapenem for over 4months for severe infectionof his foot ulcers. This is the first documented case that weknow of in which ertapenem has been safely used for thisduration of time.2. Case PresentationA 69-year-old Caucasian type 2 diabetic man presented tothe emergency department with a 2-month history of painfululcers on his left foot which had been increasing in size. Thepatient had been diagnosed with type 2 diabetes mellitus 13years earlier. This was managed with metformin, gliclazide,and rosiglitazone, although the patient admitted to nothaving taken these medications for over a year. His medicalhistory included hypertension, hypercholesterolaemia, and aprevious myocardial infarction. He had a smoking history of50 pack years, drank approximately 2 units of alcohol perweek, and was independent in all activities of daily living.The patient was started on oral flucloxacillin (500mg qds)and metronidazole (400mg tds) and discharged from theemergency department to be seen 4 days later in the diabeticfoot clinic.In the clinic, the patient was found to be hypertensive(blood pressure 164/88mmHg) and tachycardic (pulse 110beats per minute) with a temperature of 36.4◦C and oxygensaturations of 93% on room air. He weighed 64.9 kg andwas 1.67m tall, giving a body mass index of 23.3 kg/m2.Inflammatory markers in the blood were raised (normalranges in brackets): white cell count 16.2 × 109/l (4.0−11.0),neutrophils 12.4 × 109/l (2.0−7.5) and c-reactive protein46mg/l (0−6.0). His glycated haemoglobin was noted to be16.5% (4.1−6.5).Two ulcers were identified on the left foot: one on thelateral aspect of the heel, measuring 5 × 6 cm and theother on the dorsal aspect of the left hallux, measuring2 × 2 cm. Both ulcers were necrotic and sloughy andthe bone of the hallux was visible through the secondulcer. Peripheral pulses were palpable bilaterally but therewas marked peripheral neuropathy of both feet. Systemicexamination was unremarkable.Swab cultures were taken but only skin flora wasisolated (the details of this flora were not disclosed in themicrobiology report, however). A specific anaerobic culturewas not performed. Blood cultures were also sent, but nobacterial growth was detected, unsurprising given that thepatient had already been commenced on oral antibiotics.Radiograph of the left foot demonstrated loss of soft tissues2 Case Reports in MedicineTable 1: Microorganisms that ertapenem has in vitro and clinical activity against.Aerobic and facultative gram-positivemicroorganismsAerobic and facultative gram-negativemicroorganismsAnaerobic microorganismsStaphylococcus aureus (methicillinsusceptible isolates only)Escherichia coli Bacteroides fragilisStreptococcus agalactiaeHaemophilus influenzae(beta-lactamase negative isolates only)Bacteroides distasonisStreptococcus pneumoniae (penicillinsusceptible isolates only)Klebsiella pneumoniae Bacteroides ovatusStreptococcus pyogenesBacteroides thetaiotaomicronBacteroides uniformisMoraxella catarrhalis Clostridium clostridioformeProteus mirabilis Eubacterium lentumPeptostreptococcus speciesPorphyromonas asaccharolyticaPrevotella biviaat the ulcer sites but did not show any clear evidence ofosteomyelitis. However neither bone scan nor computerisedtomography (CT) was performed to confirm the absence ofosteomyelitis.The patient was admitted to a medical ward and startedon empirical intravenous antibiotics: benzylpenicillin 1.2 gqds, flucloxacillin 500mg qds, and metronidazole 500mgtds. The ulcers were debrided and daily dressings wereapplied. The patient also had a short course of maggottherapy to remove the necrotic tissue from the ulcers.Debrided tissue was regrettably not sent for culture asdebridement was performed in the podiatry department andnot on the ward under medical supervision.12 days after commencing intravenous antibiotics, oralsodium fusidate 500mg tds was also started. On the sameday, the patient was reviewed by a vascular surgeon withankle brachial pressure index (ABPI) analysis revealingmoderate arterial disease, worse in the left leg comparedto the right (ABPI 0.51 in the left leg and 0.56 in theright leg) (ABPI reference ranges: 1.0−1.3 normal, 0.9-1.0acceptable, 0.8-0.9 mild arterial disease, 0.5−0.8 moderatearterial disease, and<0.5 severe arterial disease). The vascularopinion at this stage was that if the ulcers did not heal withconservative measures then amputation would have to beconsidered.3 weeks after the introduction of intravenous antibioticsthe appearance of the foot ulcers had not improved. Inaddition, it appeared that an area of cellulitis was spreadingfrom proximal to the ulcers to the rest of the foot. Bloodtests revealed that the patient’s white cell count had risen to19.6× 109/l and the c-reactive protein had risen to 164mg/l.However, throughout this time, the patient was afebrile.The microbiology department were consulted and advisedstopping the current antibiotics and commencing the patienton intravenous ertapenem 1 g od.6 weeks after starting ertapenem, the appearance of theleft foot was improved. There was significantly less slough atthe base of the ulcers, but the heel ulcer was still necrotic.Blood tests revealed that the white cell count had fallen to14.2 × 109/l and the c-reactive protein had fallen to 9mg/l.The patient remained afebrile. The decision was made tocontinue ertapenem therapy as it was felt that the soft-tissue infection had not completely resolved and as boneinvolvement could not be ruled out, further antimicrobialtreatment would be required.After 3 months of being on ertapenem, the appearancesof the foot ulcers had improved further with the inflamma-tory markers in the blood also falling (white cell count 12.9×109/l, c-reactive protein 6mg/l) and the patient’s temperatureremaining normal. The patient was being seen in the footclinic on a weekly basis with debridement of the ulcers takingplace when appropriate. The microbiology department feltthat ertapenem should be continued as no adverse eﬀects hadbeen encountered and that the soft-tissue infection requiredfurther treatment.After over 4 months on ertapenem the ulcers had almostcompletely healed with necrotic tissue no longer visible. Thepatient’s white cell count had fallen to 12.3 × 109/l andthe c-reactive protein was 6mg/l. He had remained afebrilethroughout all this time. The patient’s glycated haemoglobinwas rechecked and had come down to 5.9%.Ertapenem was stopped after 4 months and 16 daysof therapy (137 days in total). The patient had remainedin hospital for the full duration of the ertapenem therapyto ensure compliance with all medications, so that theaﬀected limb was free from weight bearing to allow pressurerelief and to permit regular debridement of the ulcers. Thepatient was discharged home 2 weeks after the cessation ofertapenem. Vascular review before discharge documentedthat amputation no longer had to be considered at presentbut that the patient would require close followup in thecommunity and would at some point require vascularintervention.3. DiscussionFoot infections account for approximately 20% of hospitaladmissions in diabetic patients and up to 25% of allCase Reports in Medicine 3diabetics are expected to develop severe foot problems atsome point during their life [1]. Infection is usually aconsequence of foot ulcerations which typically result fromtrauma to a neuropathic foot. Other major risk factors forulcer formation are structural foot deformity and peripheralvascular disease.Diabetic foot infections are generally more severe andharder to treat than infections seen in nondiabetic patients.This is due to a number of factors including impairedmicrovascular circulation, neuropathy, anatomical alter-ations and impaired immune capacity in diabetic patients.Ertapenem, a long-acting, 1β-methyl parenteral group 1carbapenem antibiotic with a broad antibacterial spectrumwas licensed for clinical practice in Europe and the USA in2002 [2]. It has a once-daily dosing regimen and is generallywell tolerated [3]. Ertapenem is active against gram positive,gram negative, and anaerobic bacteria (Table 1) and has beenshown to be eﬀective in skin/soft-tissue infections [4].Infection of diabetic foot ulcers is usually caused byaerobic gram positive cocci, most commonly staphylococcusaureus, haemolytic staphylococci (especially group B), andcoagulase negative staphylococci. Although monomicrobialinfections may occur, it is common for these gram positivecocci to be found along with gram negative bacilli andobligate anaerobes [5, 6]. In this case, the patient did notrespond to the initial antibiotic regimen of intravenous ben-zylpenicillin, flucloxacillin, and metronidazole. This regimenlacks coverage for facultative gram negative rods, and so thefailure could have been due to the inadequate coverage forthese organisms.In this case, the only microbiology isolated was reportedas “skin flora”. A multicentre clinical trial on the bacteriologyof diabetic foot infections published in 2007 found staphylo-coccus epidermidis in nearly 50% of the coagulase negativestaphylococci isolates [7]. Citron et al. comment that S.epidermis, often dismissed as a commensal or contaminant,is now increasingly being recognised as a true pathogen indiabetic foot infections. Although the organism is innocuouson intact human skin, it can cause severe infections after itpenetrates anatomical barriers partly through the productionof proteases, peptidases, biofilms, and surface lipoproteinsthat promote host tissue adherence [7].Citron et al. go on to state that because specimensfrom most patients have polymicrobial cultures, empiricaltherapy should be relatively broad spectrum with eitherertapenem or piperacillin-tazobactem being an appropriateempirical single agent (except for methicillin resistant S.aureus infections) [7].Ertapenem has a broad spectrum of action, but it doesnot provide cover against most enterococcus or pseudomonasspecies which are often found in diabetic foot infections.This would seemingly put ertapenem at a disadvantage topiperacillin-tazobactam, which does cover these commonlyoccurring species. However, a large multicentre, double-blinded, randomised clinical trial published in 2005 demon-strated that in diabetic foot infections treatment with aonce daily dose of ertapenem produced equivalent clinicaloutcomes to treatment with a four-time daily dose ofpiperacillin-tazobactam [8].The recommended duration of antibiotic therapy indiabetic foot infections ranges from 1−4 weeks for soft-tissueinfection alone to >6 weeks for unresected osteomyelitis.The manufacturers recommend use of ertapenem for 7−14days in complicated skin infections without osteomyelitis[9]. Ertapenem was used for a total of 137 days in this case,where the presence of osteomyelitis could not be accuratelyruled out. Ertapenem was used for this duration of time asat each stage of review, it was felt that although the footinfection was improving further treatment was needed, andas there were no adverse eﬀects this length of therapy wasdeemed acceptable by both the microbiology departmentand the admitting medical team.Clearly, other factors had an important role to playin the resolution of the diabetic foot infection detailed inthis case aside from the antimicrobial treatment. Whenthe patient was initially seen in the diabetic foot clinic,he admitted to not taking his oral hypoglycaemic med-ications for over one year. Whilst he was an inpatient,these medications were restarted and subsequently led to animprovement in glycaemic control. This is reflected in thefall in glycated haemoglobin from 16.5% on admission to5.9% on discharge. In addition, the patient was not weightbearing on the aﬀected limb throughout the duration of histreatment which would have helped the healing of the footulcers through pressure relief. Also the patient’s ulcers wereregularly debrided allowing healthy tissue to emerge afternonviable tissue had been resected.This case demonstrates the safe use of ertapenem for over4months in treating infected diabetic foot ulcers. In our case,it was highly eﬀective in treating the patient’s infected ulcerswhen empirical therapies had been unsuccessful. Ertapenemhas a once-daily dosing regimen and has shown equivalentresults in the treatment of diabetic soft tissue infections tothemore widely used drug piperacillin-tazobactem. This casehighlights the fact that ertapenem could have a role as a firstline intravenous antibiotic in the treatment of diabetic footinfections and be used for long durations when required.The once-daily dosing regimen of ertapenem also makes it asuitable agent for prolonged outpatient or home intravenousantibiotic therapy.ConsentThe patient described in the case has given informed consentfor the report to be published.References[1] B. A. Cunha, “Antibiotic selection for diabetic foot infections:a review,” Journal of Foot and Ankle Surgery, vol. 39, no. 4, pp.253–257, 2000.[2] O. Burkhardt, H. Derendorf, and T. Welte, “Ertapenem: thenew carbapenem 5 years after first FDA licensing for clinicalpractice,” Expert Opinion on Pharmacotherapy, vol. 8, no. 2, pp.237–256, 2007.[3] G. M. Keating and C. M. Perry, “Ertapenem: a review of its usein the treatment of bacterial infections,” Drugs, vol. 65, no. 15,pp. 2151–2178, 2005.4 Case Reports in Medicine[4] H. M. Wexler, “In vitro activity of ertapenem: review of recentstudies,” Journal of Antimicrobial Chemotherapy, vol. 53, S2, pp.ii11–ii21, 2004.[5] L. J. Wheat, S. D. Allen, M. Henry et al., “Diabetic footinfections. Bacteriologic analysis,” Archives of Internal Medicine,vol. 146, no. 10, pp. 1935–1940, 1986.[6] P. R. Cavanagh, B. A. Lipsky, A. W. Bradbury, and G. Botek,“Treatment for diabetic foot ulcers,” Lancet, vol. 366, no. 9498,pp. 1725–1735, 2005.[7] D.M. Citron, E. J. C. Goldstein, C. V.Merriam, B. A. Lipsky, andM. A. Abramson, “Bacteriology of moderate-to-severe diabeticfoot infections and in vitro activity of antimicrobial agents,”Journal of Clinical Microbiology, vol. 45, no. 9, pp. 2819–2828,2007.[8] B. A. Lipsky, D. G. Armstrong, D. M. Citron, A. D.Tice, D. E. Morgenstern, and M. A. Abramson, “Ertapenemversus piperacillin/tazobactam for diabetic foot infections(SIDESTEP): prospective, randomised, controlled, double-blinded, multicentre trial,” Lancet, vol. 366, no. 9498, pp. 1695–1703, 2005.[9] http://emc.medicines.org.uk/document.aspx?documentId=10421.Submit your manuscripts athttp://www.hindawi.comStem CellsInternationalHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014MEDIATORSINFLAMMATIONofHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Behavioural NeurologyEndocrinologyInternational Journal ofHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Disease MarkersHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014BioMed Research InternationalOncologyJournal ofHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Oxidative Medicine and Cellular LongevityHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014PPAR ResearchThe Scientific World JournalHindawi Publishing Corporation http://www.hindawi.com Volume 2014Immunology ResearchHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Journal ofObesityJournal ofHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014 Computational and  Mathematical Methods in MedicineOphthalmologyJournal ofHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Diabetes ResearchJournal ofHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Research and TreatmentAIDSHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Gastroenterology Research and PracticeHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Parkinson’s DiseaseEvidence-Based Complementary and Alternative MedicineVolume 2014Hindawi Publishing Corporationhttp://www.hindawi.com

Case Reports in Medicine

Prolonged Use of Ertapenem to Treat Infected Diabetic Foot Ulcers

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Prolonged Use of Ertapenem to Treat Infected  Diabetic Foot Ulcers

Antibiotic selection for diabetic foot infections: a review,”

Bacteriology of moderate-to-severe diabetic foot infections and in vitro activity of antimicrobial agents,”

Ertapenem versus piperacillin/tazobactam for diabetic foot infections (SIDESTEP): prospective, randomised, controlled, doubleblinded, multicentre trial,”

Ertapenem: a review of its use in the treatment of bacterial infections,”

In vitro activity of ertapenem: review of recent studies,”

Treatment for diabetic foot ulcers,”

u r k h a r d t ,H .D e r e n d o r f ,a n dT .W e l t e ,“ E r t a p e n e m :t h e new carbapenem 5 years after ﬁrst FDA licensing for clinical practice,” Expert Opinion on Pharmacotherapy,v o l .8 ,n o .2 ,p p .

W h e a t ,S .D .A l l e n ,M .H e n r ye ta l . ,“ D i a b e t i cf o o t infections.Bacteriologic analysis,”

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Prolonged Use of Ertapenem to Treat Infected Diabetic Foot Ulcers

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