01 November 2023: Articles
Successful Outpatient Treatment of Severe Diabetic-Foot Myositis and Osteomyelitis Caused by Extensively Drug-Resistant with Teicoplanin plus Rifampicin: A Case Report
Mistake in diagnosis, Management of emergency care, Rare diseaseGeorgios S. Papaetis12ABDEF*, Panagiotis T. Doukanaris3AB, Eleni S. Stylianou4AB, Michalis S. Neofytou5AB
Am J Case Rep 2023; 24:e941337
BACKGROUND: Foot ulcers are high-morbidity and debilitating complications of diabetes mellitus, and carry significantly increased rates of associated major amputations. They contribute to significantly worse quality of life. Osteomyelitis is a frequent complication of diabetic foot ulcers, since bacteria can contiguously spread from soft tissues to the bone, involving the cortex first and then the bone marrow. Unfortunately, clinically unsuspected osteomyelitis is frequent in persisting diabetic foot ulcers. It is associated with limb amputations and increased mortality.
CASE REPORT: We describe a 76-year-old man with long-standing insulin-treated type 2 diabetes, who experienced extensively drug-resistant Enterococcus faecalis diabetic foot myositis and osteomyelitis associated with sepsis. He was successfully treated with surgical debridement combined with the administration of teicoplanin plus rifampicin in the outpatient setting, completing, in total, a twelve-week course of antibiotic therapy.
CONCLUSIONS: Clinically unsuspected osteomyelitis in patients with persisting diabetic foot ulcers has been associated with infections from highly resistant bacteria. Early and accurate diagnosis of diabetic foot osteomyelitis, as well as proper therapeutic approach (antimicrobial and surgical), is of great importance to reduce the risk of minor and major amputations, septic shock leading to multiple organ failure, and overall mortality.
Keywords: case reports, Diabetic Foot, Enterococcus faecalis, osteomyelitis, Teicoplanin
Diabetic foot ulcer (DFU) is defined as a localised skin injury and/or an injury to the underlying tissue, below the ankle, in patients with diabetes mellitus . Unfortunately, most longitudinal epidemiological studies suggest that a considerable number of diabetic patients will experience DFUs during their lives . The International Diabetes Federation emphasizes that approximately 9.1–26.1 million patients with diabetes mellitus will develop DFUs every year, while the lifetime risk of patients with both type 1 and type 2 diabetes (T2D) is as high as 34% [2,3]. Several risk factors have been closely associated with the evolution of DFUs and other foot lesions (lower extremity infections, necrotizing fasciitis, and gangrene) such as: (i) trauma; (ii) inadequate glycaemic control; (iii) peripheral arterial disease (PAD) of the lower extremities; (iv) peripheral neuropathy and subsequent loss of protective sensation; (v) inadequate foot care; (vi) foot deformities such as Charcot neuroosteoarthropathy; and (vii) diabetes-associated suppressed immune function .
Diabetic foot osteomyelitis (DFO) is a high-morbidity and debilitating complication that carries significantly increased rates of associated major amputations and mortality; it contributes to significantly worse quality of life to the affected population [2–4]. It is a frequent complication of DFUs, since bacteria can contiguously spread from the soft tissues to the bone, involving the cortex first and then the bone marrow [2,5]. The forefoot is more frequently affected (90%), followed by the midfoot (5%), and finally the hindfoot (5%), while the amputation risk above the ankle is significantly higher for hind-foot infections (50%) rather than midfoot (18.5%) or forefoot (0.33%) infections [1,2,5,6]. We report a case of a 76-year-old man with long-standing insulin-treated T2D, who experienced severe, extensively drug-resistant (XDR)
A 76-year-old man presented to our clinic with fever, pain in his left lower foot, and altered consciousness. His past medical history was significant for: (i) long-standing T2D diagnosed 20 years previously and treated with metformin 1000 mg daily, empagliflozin 10 mg daily, and basal-bolus insulin therapy (insulin glargine 45 units administered subcutaneously daily and insulin glulisine administered subcutaneously before his main meals, the dose of which was adjusted according to the carbohydrate content of his meals, his premeal glucose levels, and his daily physical activity); (ii) coronary artery disease, with coronary artery bypass grafting for symptomatic 3-vessel disease 11 years previously; (iii) PAD of the lower limbs diagnosed by color and pulsed-wave Doppler ultrasound (Fontaine classification: stage I); (iv) diabetic neuropathy of the lower limbs (abnormal 10 g monofilament and biothesiometer); (v) lumbar spine surgery 2 years previously; and (vi) obesity. His body mass index was 32 kg/m2.
His wife reported a 15-month history of a DFU in his left lower foot that caused swelling and tenderness. During this time, he received several courses of conservative sharp wound debridement together with the administration of several courses of antibiotics (including levofloxacin, clindamycin, doxycycline, and metronidazole), experiencing intervals of remissions and recurrences. Three months before his presentation, ampicillin-sensitive
His physical examination showed that he experienced all 3 quick sepsis-related organ failure assessment (SOFA) criteria for sepsis: (i) altered mentation (Glasgow Coma Scale score: 10); (ii) respiration rate of 28 breaths/minute; and (iii) systolic blood pressure of 90 mmHg . His full SOFA score was 4. His body temperature was 39°C and his heart rate was 120 beats/ minute. Except for swelling, erythema, local warmth, and tenderness of his left lower foot, due to the presence of a DFU in the area of the fifth metatarsal bone, the rest of the clinical examination was unremarkable (Figure 1). Results of his laboratory investigations showed mild anemia (hemoglobulin: 12.2 g/dL) and white blood cell count of 11 550/mm3 (neutrophils: 84%). The erythrocyte sedimentation rate was 95 mm/h, and the C-reactive protein level was 14.3 mg/dL. His glycated hemoglobin (A1C) was 8.6%. All other laboratory values were within normal limits except for renal function markers: serum urea and creatinine levels were 85 mg/dL and 1.6 mg/dL, respectively. Urine analysis disclosed mild microscopic haematuria. The urine culture was negative. Laboratory tests for hepatitis B surface antigen (HBsAg) and sexually transmitted infections were negative. The purified protein derivative skin test was also negative.
His electrocardiogram revealed sinus tachycardia. Chest radiography did not disclose any abnormal findings, while abdominal ultrasound revealed hyperechogenic liver suggesting nonalcoholic fatty liver disease. The transthoracic echocardiogram disclosed global mild reduction of the ejection fraction (EF: 45%). Magnetic resonance imaging (MRI) of the left lower foot was performed (Figure 2). Contrast-enhanced T1 weighted fat saturation MRI in the coronal and axial planes of the foot showed marked contrast enhancement of the distal 5th metatarsal bone and proximal phalanx, with signs of early destruction of the articular surfaces of the metatarso-phalangeal joint space. There was also prominent contrast enhancement of the plantar and dorsal muscles of the foot extending from the fifth to the second toe, suggestive of extensive myositis (Figure 2A). The axial image showed a sinus tract extending to a subcutaneous abscess adjacent to the base of the 5th meta-tarsal bone with an overlying skin ulcer (Figure 2B).
The patient was hemodynamically stabilized. Meropenem 1 g intravenously every 8 h and daptomycin 10 mg/kg/day were started. Two sets of blood cultures, for bacteria (aerobic and anaerobic) and fungi were obtained immediately after admission of the patient and surgical removal of all devitalized and necrotic soft tissues. Cultures were obtained from deep tissues that were removed from the area closest to the bone, as well as from a small bone specimen. The
Metformin and empagliflozin were stopped during his hospitalization. He was treated only with insulin therapy, which was adjusted as needed.
The patient improved and became afebrile 96 hours after his admission. He gradually regained his normal state of consciousness and mobility. All renal function markers eventually became normal (serum urea and creatinine levels were 35 mg/dL and 0.9 mg/dL, respectively, 2 days before he left the hospital). He was then discharged and treated in the outpatient setting with intravenous teicoplanin in a daily dose of 10 mg/kg plus oral rifampicin. He was advised to restart metformin and empagliflozin and intensify his insulin treatment. He experienced regular cautious sharp debridement to remove slough and non-viable necrotic tissues. He was advised to use offloading foot-wear, to reduce his weight-bearing activity and increase non-weight-bearing activity (mainly moderate intensity stationary cycling). After 6 weeks of treatment, CRP and procalcitonin levels declined to normal levels. His renal status remained within normal limits and urine analysis was also normal. Erythrocyte sedimentation rate, a marker that has been associated with remission or cure of DFO, was normalized after 8 weeks of therapy . The progress of wound healing of his DFU is shown in Figure 3. He eventually completed, in total, a 12-week course of antibiotic therapy. A1C at the end of his antimicrobial therapy dropped to 7.4%. No recurrence was found 2 years after the end of his antimicrobial therapy. Lack of cooperation from the patient was the only reason for not repeating MRI of his left foot.
DFO is a serious complication of DFUs. Unfortunately, clinically unsuspected DFO is frequent in persisting DFUs. As was the case with our patient, DFO has been associated with suboptimal and inappropriate antibiotic administration, as well as with infections from highly resistant pathogens and life-threatening complications. In contrast to our patient, most of the infections in other cases of DFO are polymicrobial [2,6,9]. The most common pathogens isolated are:
Magiorakos et al defined XDR
Several reasons could explain the high resistance of the
OPAT has several advantages, including earlier discharge from the hospital, reduced length of hospital stay, lower cost, and overall improved patient satisfaction . Teicoplanin, ceftriaxone, and ertapenem are common antibacterial agents used in this setting [28,29]. Teicoplanin was found to be an attractive antimicrobial that can be administered in the OPAT setting, in view of its favorable dosing regimen, low clinical failure rates, and acceptable safety profile . Furthermore, rifampicin is a potent bactericidal drug that is effective against several gram-positive bacteria, and also displays good bone penetration . It is well absorbed when taken orally and has high activity against biofilm-associated organisms. In cases of rapid development of resistance, this old agent is an important candidate for combination therapies . Rifampicin-based combinations with several antimicrobials (including teicoplanin) have highlighted
Cultures taken from soft tissues and pus have predominantly polymicrobial flora, while bone cultures are mainly monomicrobial [2,4,11]. A study in 60 consecutive patients with infected DFUs showed that bacteria isolated from soft tissues were different from those in pus and bone in 54% and 57%, respectively, of the population enrolled . However, in our patient, both cultures taken from the deep tissues closest to the bone and from a small specimen of the infected bone suggested
Clinically unsuspected DFO is frequent in persisting DFUs. It has been associated with suboptimal and inappropriate antibiotic administration, as well as infections from highly resistant pathogens and life-threatening complications. Early and accurate diagnosis, as well as proper therapeutic approach (antimicrobial and surgical), is of great importance to reduce the risk of minor and major amputations, septic shock leading to multiple organ failure, and overall mortality.
FiguresFigure 1.. Diabetic foot ulcer, located in area of the left fifth metatarsal bone, at the patient’s presentation. Figure 2.. MRI scans of the left lower foot. (A) Contrast-enhanced T1-weighted fat saturation MRI in the coronal plane of the foot shows marked contrast enhancement of the distal fifth metatarsal bone and proximal phalanx with signs of early destruction of the articular surfaces of the metatarso-phalangeal joint space (white arrow). There was also prominent contrast enhancement of the plantar and dorsal muscles of the foot extending from the fifth to the second toe suggestive of extensive myositis. (B) Contrast-enhanced T1-weighted fat saturation MRI in the axial plane of the foot. The axial image showed a sinus tract extending to a subcutaneous abscess adjacent to the base of the fifth metatarsal bone, with an overlying skin ulcer (asterisk). MRI – magnetic resonance imaging. Figure 3.. Progression of wound healing of the DFU: (A) 4 weeks; (B) 6 weeks; (C) 8 weeks; (D) 10 weeks after the beginning of antimicrobial therapy. DFU – diabetic foot ulcer.
1.. Arias M, Hassan-Reshat S, Newsholme W, Retrospective analysis of diabetic foot osteomyelitis management and outcome at a tertiary care hospital in the UK: PLoS One, 2019; 14(5); e0216701
2.. Sorber R, Abularrage CJ, Diabetic foot ulcers: Epidemiology and the role of multidisciplinary care team: Semin Vasc Surg, 2021; 34(1); 47-53
3.. Armstrong DG, Boulton AJM, Bus SA, Diabetic foot ulcers and their recurrence: N Engl J Med, 2017; 376(24); 2367-75
4.. Bajaj S, Mahajan A, Grover S, Peripheral vascular disease in patients with diabetic foot ulcers – an emerging trend: A prospective study from North India: J Assoc Physicians India, 2017; 65(5); 14-17
5.. Faglia E, Clerici G, Caminiti M, Influence of osteomyelitis location in the foot of diabetic patients with transtibial amputation: Foot Ankle Int, 2013; 34(2); 222-27
6.. Giurato L, Meloni M, Izzo V, Uccioli L, Osteomyelitis in diabetic foot: A comprehensive overview: World J Diabetes, 2017; 8(4); 135-42
7.. Singer M, Deutschman CS, Seymour CW, The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3): JAMA, 2016; 315(8); 801-10
8.. Lazaro-Martinez JL, Aragon-Sanchez J, Garcia-Morales E, Antibiotics versus conservative surgery for treating diabetic foot osteomyelitis: A randomized comparative trial: Diabetes Care, 2014; 37(3); 789-95
9.. Reiber GE, Pecoraro RE, Koepsell TD, Risk factors for amputation in patients with diabetes mellitus. A case-control study: Ann Intern Med, 1992; 117(2); 97-105
10.. Nicolau DP, Stein GE, Therapeutic options for diabetic foot infections: A review with an emphasis on tissue penetration characteristics: J Am Podiatr Med Assoc, 2010; 100(1); 52-63
11.. Lipsky BA, Uçkay İ, Treating diabetic foot osteomyelitis: A practical state-of-the-art update: Medicina (Kaunas), 2021; 57(4); 339
12.. Charles PG, Uçkay I, Kressmann B, The role of anaerobes in diabetic foot infections: Anaerobe, 2015; 34; 8-13
13.. Zenelaj B, Bouvet C, Lipsky BA, Uçkay I: Int J Low Extrem Wounds, 2014; 13(4); 263-72
14.. Eleftheriadou I, Tentolouris N, Argiana V: Drugs, 2010; 70(14); 1785-97
15.. Pfirman KS, Haile R: Am J Case Rep, 2018; 19; 224-28
16.. Citron DM, Goldstein EJ, Merriam CV, Bacteriology of moderate-to-severe diabetic foot infections and in vitro activity of antimicrobial agents: Clin Microbiol, 2007; 45(9); 2819-28
17.. Jneid J, Cassir N, Schuldiner S, Exploring the microbiota of diabetic foot infections with culturomics: Front Cell Infect Microbiol, 2018; 8; 282
18.. Krawczyk B, Wityk P, Gałęcka M, Michalik M: Microorganisms, 2021; 9(9); 1900
19.. Esmail MAM, Abdulghany HM, Khairy RM: Infect Dis (Auckl), 2019; 12; 1178633719882929
20.. Li X, Du Z, Tang Z, Distribution and drug sensitivity of pathogenic bacteria in diabetic foot ulcer patients with necrotizing fasciitis at a diabetic foot center in China: BMC Infect Dis, 2022; 22(1); 396
21.. Magiorakos AP, Srinivasan A, Carey RB, Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: An international expert proposal for interim standard definitions for acquired resistance: Clin Microbiol Infect, 2012; 18(3); 268-81
22.. Loupa CV, Lykoudi E, Meimeti E, Successful treatment of diabetic foot osteomyelitis with dalbavancin: Med Arch, 2020; 74(3); 243-45
23.. Patel R, Clinical impact of vancomycin-resistant enterococci: J Antimicrob Chemother, 2003; 51(Suppl. 3); iii13-iii21
24.. Papaetis GS, Politou VN, Panagiotou SM, Recurrent cellulitis-like episodes of the lower limbs and acute diarrhea in a 30-year-old woman: A case report: Am J Case Rep, 2021; 22; e932732
25.. Newman LG, Waller J, Palestro CJ, Unsuspected osteomyelitis in diabetic foot ulcers. Diagnosis and monitoring by leukocyte scanning with indium in 111 oxyquinoline: JAMA, 1991; 266(9); 1246-51
26.. Schwegler B, Stumpe KD, Weishaupt D, Unsuspected osteomyelitis is frequent in persistent diabetic foot ulcer and better diagnosed by MRI than by 18F-FDG PET or 99mTc-MOAB: J Intern Med, 2008; 263(1); 99-106
27.. Mitchell ED, Czoski Murray C, Meads D, Clinical and cost-effectiveness, safety and acceptability of community intravenous antibiotic service models: CIVAS systematic review: BMJ Open, 2017; 7(4); e013560
28.. Marks M, Bell LCK, Jones I, Clinical and economic impact of implementing OVIVA criteria on patients with bone and joint infections in out-patient parenteral antimicrobial therapy: Clin Infect Dis, 2020; 71(1); 207-10
29.. Papaetis GS, Petridis TA, Karvounaris S: Am J Case Rep, 2022; 23; e936179
30.. Dabrowski H, Wickham H, De S, Clinical outcomes of teicoplanin use in the OPAT setting: Int J Antimicrob Agents, 2020; 55(3); 105888
31.. O’Driscoll T, Crank CW, Vancomycin-resistant enterococcal infections: Epidemiology, clinical manifestations, and optimal management: Infect Drug Resist, 2015; 8; 217-30
32.. Skinner K, Sandoe JAT, Rajendran R: Int J Antimicrob Agents, 2017; 49(4); 507-11
33.. Wilson BM, Bessesen MT, Doros G, Adjunctive rifampin therapy for diabetic foot osteomyelitis in the veterans health administration: JAMA Netw Open, 2019; 2(11); e1916003
34.. Bessesen MT, Doros G, Henrie AM, A multicenter randomized placebo-controlled trial of rifampin to reduce pedal amputations for osteomyelitis in veterans with diabetes (VA INTREPID): BMC Infect Dis, 2020; 20(1); 23
35.. Parvez N, Dutta P, Ray P, Microbial profile and utility of soft tissue, pus, and bone cultures in diagnosing diabetic foot infections: Diabetes Technol Ther, 2012; 14(8); 669-74
36.. Malone M, Bowling FL, Gannass A, Deep wound cultures correlate well with bone biopsy culture in diabetic foot osteomyelitis: Diabetes Metab Res Rev, 2013; 29(7); 546-50
37.. Tone A, Nguyen S, Devemy F, Six-week versus twelve-week antibiotic therapy for nonsurgically treated diabetic foot osteomyelitis: A multicenter open-label controlled randomized study: Diabetes Care, 2015; 38(2); 302-7
38.. Lipsky BA, Senneville É, Abbas ZG, Guidelines on the diagnosis and treatment of foot infection in persons with diabetes (IWGDF 2019 update): Diabetes Metab Res Rev, 2020; 36(Suppl, 1); e3280
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