G Model
DSX-429; No. of Pages 4 Diabetes & Metabolic Syndrome: Clinical Research & Reviews xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Diabetes & Metabolic Syndrome: Clinical Research & Reviews journal homepage: www.elsevier.com/locate/dsx
Original Article
Antibiotic therapy for diabetic foot infections in a tertiary care hospital in Jakarta, Indonesia Maksum Radji a,*, Corry Shirleyana Putri a, Siti Fauziyah b a b
Laboratory of Microbiology and Biotechnology, Faculty of Pharmacy, University of Indonesia, Depok 16424, Indonesia Department of Pharmacy, Dr. Mintohardjo Navy Hospital, Bendungan Hilir No. 17, Jakarta 10210, Indonesia
A R T I C L E I N F O
A B S T R A C T
Keywords: Diabetic foot infections Antibiotic Clinical pharmacy Indonesia
Aims: The purpose of this study was to determine the microbiology of diabetic foot infections and to assess the antibiotic susceptibility patterns. Materials and methods: A cross sectional retrospective study of 35 patients with diabetic foot infections hospitalized at the internal medicine clinic of Dr. Mintohardjo Navy Hospital, Jakarta. The data were collected from patient medical records retrospectively. The classification of the diabetic foot infections was evaluated according to Meggit–Wagner’s Classification. Identification of causative microorganisms was performed by standard microbiologic methods. Antibiotic susceptibility testing was performed using disk-diffusion method. Results: During January to December 2012, a total of 288 of diabetic patients were admitted to hospital, and 35 patients had diabetic foot infections. According to Meggit–Wagner’s classification the most common disease was grade 3 in 31.4% patients, followed by grade 2 in 25.7%, and grade 4 in 17.3% of patients. Conservative diabetic control care was carried out in 37.1% of patients, and surgical intervention was carried out in 62.9% of patients. A total of 59 pathogens were identified. The most common infecting microorganism isolated on pus cultures was Staphylococcus aureus (47.5%), followed by Pseudomonas spp (16.9%), E. coli (10.2%), Streptococcus spp. (8.5%), Enterobacter spp. (7.0%), Proteus spp. (6.7%), and Acinetobacter spp. (3.2%). Overall, 37.2% of the diabetic foot infection caused by a single microorganism, and 62.8% had polymicrobial infections. The most frequently administrated antibiotic was ceftriaxone (40.0%), followed by ciprofloxacin (11.4%), and meropenem (8.6%). Conclusion: Diabetic foot infections (62.8%) were polymicrobial. S. aureus was most commonly found in the foot infection. Most of the microorganisms isolated from diabetic foot infection were resistant to many types of antibiotics. ß 2014 Diabetes India. Published by Elsevier Ltd. All rights reserved.
1. Introduction Diabetes mellitus is a serious and complex illness that affects almost all the vital organs in the body. Approximately 382 million people worldwide suffer from diabetes and it has been estimated that it will increase to 592 million by 2035. In 2013, diabetes caused more than 5.1 million deaths, where every 6 s a person dies from diabetes [1]. The disease is known to have many complications and one of the most severe is diabetic foot infection that affects 15% of people with diabetes, and leading to amputation [2]. Every year, more than one million diabetes patients require limb amputation [3].
* Corresponding author. E-mail address: [email protected] (M. Radji).
Indonesia is the seventh largest country in the case of diabetes mellitus incidence in the world after China, India, USA, Brazil, Russia and Mexico. The incidence of diabetes mellitus in Indonesia is estimated at about 8.5 million in 2013 [1]. For the treatment of diabetes mellitus, the Infectious Diseases Society of America (IDSA) has recommended a guideline that the treatment of diabetic foot infection should be performed by a team of multidisciplinary diabetic foot care consisting of an infectious disease specialist, specialist of clinical microbiology, foot surgeons, and wound-care specialists [4]. Diabetic foot infections are often caused by a number of infecting microorganisms. Staphylococcus aureus, Streptococcus pyogenes, Staphylococcus epidermidis, E. coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter spp, Proteus spp., and Enterococcus spp. are some of the frequent pathogens contribute to progressive tissue damage [4–7]. The presence of obligate anaerobes associated with
http://dx.doi.org/10.1016/j.dsx.2014.09.006 1871-4021/ß 2014 Diabetes India. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Radji M, et al. Antibiotic therapy for diabetic foot infections in a tertiary care hospital in Jakarta, Indonesia. Diab Met Syndr: Clin Res Rev (2014), http://dx.doi.org/10.1016/j.dsx.2014.09.006
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DSX-429; No. of Pages 4 M. Radji et al. / Diabetes & Metabolic Syndrome: Clinical Research & Reviews xxx (2014) xxx–xxx
2
necrosis, gangrene, or ischemic tissue and usually occurs in severe chronic infections [4,8,9]. Diabetic foot infections caused by bacteria such as multi-drug-resistant methicillin-resistant S. aureus usually occurs in patients who are admitted to the hospital and in the community with a high prevalence of drug resistance [4,8,9]. The increasing of diabetic foot infections caused by multidrugresistant pathogen is responsible for the duration of hospitalization, morbidity and mortality of diabetic patients [6]. The optimal treatment of diabetic foot infection is still a matter of concern. This diabetic complication is very difficult to treat if proper protocol is not followed [10–12]. However, most researchers agree that the management of this infection requires isolation and identification of microbial flora, appropriate antibiotic therapy according to the local sensitivity pattern, proper selection and identification of chronic complications and appropriate surgical intervention for this complication [7]. Educating diabetic patients is one of another way in preventing diabetic foot infections and to improve the outcomes of therapy. Empirical broad-spectrum antibiotic regimens can be administrated. However, the sensitivity tests of bacterial pathogens should be performed to assist in the selection of appropriate antibiotic treatment regimens [13]. Narrow-spectrum antibiotics can be selected for acute or less severe infection, while the broadspectrum antibiotics should be used in cases of chronic or severe infection [14]. The appropriate diabetic foot infections care could prevent more than 40% of amputations [15]. In Indonesia, there has been a limited study of the diabetic foot infections care, especially the control of infection by appropriate antibiotics. Therefore, the purpose of this study was to evaluate the antibiotic treatment for diabetic foot infection in Dr. Mintohardjo Navy Hospital, Jakarta Indonesia.
2. Patients and methods A retrospective cross-sectional study was carried out at tertiary care Navy Hospital of Dr Mintohardjo, Jakarta, Indonesia. Demographic and clinical data were collected retrospectively from patient medical records who had admitted to hospital during January to December 2012. The inclusion criteria were inpatients that hospitalized at internal medicine clinic, suffered diabetic foot infection. Out patients and patients with incomplete information of medical records were excluded from the study. The classification of the diabetic foot infections were evaluated according to Meggit– Wagner’s Classification [16,17]. 2.1. Isolation of bacteria and antibiotic susceptibility test All foot ulcer samples were collected aseptically and were plated right after the collection. Identification of causative microorganisms was performed by standard microbiologic methods. Antibiotic susceptibility testing was performed using diskdiffusion method. The results were interpreted according to the guidelines of the Clinical and Laboratory Standards Institute [18].
27.80%
5.60%
16.70% 4 40-50 years 5 51-60 years 6 61-70 years 49.80
> 70 years
Fig. 1. The age range of diabetic foot patients.
3. Results During January to December 2012, a total of 288 of diabetic patients were admitted to hospital, of which 35 diabetic foot infection patients were hospitalized and have been considered as qualified for inclusion criteria. We found that diabetic foot infection affected males slightly more frequent (54.3%) as compared to females (45.7%); the male to female ratio was 1.18:1. The age ranged of diabetic foot patients was from 46 to 75 years, and the most common age groups of diabetic foot patients was the age group of 51–60 years, followed by the 61–70 years age group as shown in Fig. 1. The grade of diabetic foot infection according to Meggit–Wagner’s classification is shown in Table 1. The commonest disease was grade 3 that comprised of 31.4% patients, followed by grade 2 in 25.7%, and grade 4 in 17.3% of patients. Conservative diabetic control care was carried out in 37.1% patients and surgical intervention was carried out in 62.9% of patients. We found that the most of the diabetic foot patients were hospitalized for 6–10 days as shown in Fig. 2. A total of 59 pathogens were identified with an average of 1.68 microorganisms per patient. The most common infecting microorganism isolated on pus cultures was S. aureus (47.5%), followed by Pseudomonas spp (16.9%), E. coli (10.2%), Streptococcus spp. (8.5%), Enterobacter spp. (7.0%), Proteus spp. (6.7%), and Acinetobacter spp. (3.2%). Overall, 37.2% of the cultures were a single microorganism, and 62.8% had mixed infections. The results of sensitivity patterns of the isolated microorganisms are shown in Table 2.
4. Discussion Diabetes mellitus is a global health problem which diabetic foot infection is one of the most serious complications [19]. This complication is more common in the older age group compared with younger ones. In our study we found that the most commonly affected age group was between 50 and 60 years. This result was similar to previous studies that diabetic foot infections often occur in patients older than 50 years [7,10,20]. Various studies show that diabetic foot infection has the longest hospital stay as compared to other complications of diabetes
Table 1 The grade frequency of diabetic foot infection according to the Meggit–Wagner’s Classification of Diabetic Foot infections. Grade
Disease
Treatment management
Frequency (%)
0 1 2
No ulcer in a risk foot Superficial ulcer Deep ulcer, involve ligaments and muscles, but no bone involvement Deep ulcer with bone involvement often with osteomyelitis Localized gangrene Extensive gangrene of the whole foot
Prevention Antibiotics, glycemic control, and local wound care Antibiotics and glycemic control, adequate perfusion, local wound care and regular debridement Antibiotics and glycemic control, debridements, and off-loading of the foot Extensive debridement with or without amputation Amputation
0 11.4 25.7
3 4 5
31.4 17.3 14.2
Please cite this article in press as: Radji M, et al. Antibiotic therapy for diabetic foot infections in a tertiary care hospital in Jakarta, Indonesia. Diab Met Syndr: Clin Res Rev (2014), http://dx.doi.org/10.1016/j.dsx.2014.09.006
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Fig. 2. The duration of hospitalization of diabetic foot infection patients.
[11,12]. We found that the most of the diabetic foot patients were hospitalized for about 2 weeks. However some patients were hospitalized more than 4 weeks. Approximately one third of patients (37.1%) were managed conservatively while the remaining patients were managed by surgical intervention, including wound dressing, debridement and extensive debridement in 46.2% and amputation in (16.7%). The commonest microorganism isolated on pus cultures was S. aureus (47.5%). This result was similar to some other studies that S. aureus is the most common bacteria isolated from the cultures of diabetic foot infections [4,9,21–24]. However our results were in contrast to previous local study conducted at Koja Regional General Hospital, Jakarta that P. aeruginosa was the most frequent bacteria isolated form diabetic foot infections [25]. Our findings showed that 62% of patients were infected by two or more pathogens. This result was consistent to other studies that most diabetic foot infections are generally a poly-microbial infection. Mixed pathogens commonly found in wound infections [5,7,26,27]. In this study, the most frequent administrated antibiotic was ceftriaxone (40.0%), followed by ciprofloxacin (11.4%), and meropenem (8.6%). However, all infecting bacteria had showed low sensitivity against ceftriaxone. Regarding to the susceptibility patterns, we found that about 10% of Staphylococcus were MRSA as shown in Table 2. Most of the isolated bacteria showed resistance against some antibiotics and therefore, we assumed that monotherapy might not be the best management for therapy of diabetic foot infection. The increasing incidence of multi-drug resistant organisms is a potential risk factor in management of diabetic foot infections. The local pattern of bacterial etiology and their susceptibility is very important in choosing empirical antibiotic therapy for diabetic foot infections. In term of antibiotic therapy, the guidelines of antimicrobials management for diabetic foot infections have been established
3
worldwide [4,14,28]. However, these guidelines have not been fully used in the treatment of diabetic foot infections [29]. Generally, empirical antibiotic treatment can be administrated for diabetic foot infections according to the severity of infection. Narrow-spectrum antibiotics may be given in cases of acute or less severe infections, while the broad-spectrum antibiotics should be used parenterally in cases of chronic or severe infections [14]. In mild infections of outpatients should not be treated with topical or systemic antibiotics, and should be treated with oral antibiotics for 1–2 weeks [4]. S. aureus and beta-hemolytic Streptococcus are the most common bacteria found in patients with mild to moderate diabetic foot infection [4,8,9,14]. For mild infections could use oral antibiotics such as cephalexin, amoxicillin/clavulanate, levofloxacin or dicloxacillin, and antibiotics that cover methicillin resistant S. aureus (MRSA) include clindamycin, doxycycline, and timethoprim/sulfamethoxazole [4,14]. For moderate infections can be treated initially with oral antibiotics or with parenteral antibiotics, followed by oral therapy for 1–3 weeks. Whereas severe infections requiring hospitalization and treatment with parenteral antibiotics followed by oral therapy, for 2–4 weeks [4]. Some potential broad-spectrum antibiotic for use in diabetic foot infections such as Piperacillin/tazobactam, meropenem, doripenem, ertapenem, aztreonam, levofloxacin, ciprofloxacin, ceftriaxone, clindamycin, vancomycin, daptomycin, linezolid, imipenem, and tigecycline [4,14]. Piperacillin/tazobactam, doripenem and meropenem have been shown to have excellent activity against the majority of bacterial isolates from diabetic foot infection including P. aeruginosa [14]. Other consideration in the treatment of diabetic foot infection is the use of topical antibiotics. Although current use of topical antibiotics is not recommended especially for patients infected chronic wounds, but may have a role in certain conditions [19,30]. Topical antibiotics should always be preceded by debridement and can be considered to be given to subclinical infection or to assist in removing bacterial biofilms, which have led to persistent wound infection [31]. Diabetic foot infection is one of some complication of diabetes that is very difficult to overcome, and therefore the management of diabetic foot infection should be performed by a multidisciplinary approach [4,19,32]. Pharmacists, as the most accessible health care professional has a central role in helping to prevent diabetic foot infections. Pharmacists should play a role in empowering and educating patients with diabetes to maintain optimal blood glucose levels and monitor medication adherence of patient. In addition pharmacists should be involved with other health care professionals to choose the most appropriate antimicrobial regimen for the patient, including dosage, route of administration,
Table 2 Sensitivity patterns of isolated microorganisms. Microorganism
Antibiotic sensitivity pattern (%) AMP
AK
CFP
CTX
CPR
CAZ
CRO
C
CIP
E
FOS
CN
IMP
K
MEM
NET
OFX
FEP
VA
Streptococcus spp S. aureus MRSA Peudomonas spp E. coli Proteus spp Enterobacter spp Acinetobacter spp
100
100
70
50
80
70
40
100
90
70
90
100
100
70
100
90
100
100
100
100 0 10
100 0 70
60 0 10
80 0 20
70 0 10
60 0 30
50 0 10
90 40 30
70 0 60
60 0 40
80 30 70
90 0 60
100 20 80
60 0 70
100 20 90
80 0 80
80 40 80
100 0 80
100 100 0
60 30 10
80 70 30
60 60 20
70 50 40
70 40 50
80 70 50
60 60 40
100 90 80
90 60 40
70 70 30
70 70 70
50 80 70
100 80 70
60 50 40
100 80 60
80 70 30
100 80 60
90 80 70
20 10 20
10
60
40
50
60
30
40
70
40
60
80
50
40
50
40
60
40
50
10
AMP = ampicillin; AK = amikacin; CFP = cefoperazon; CTX = cefotaxime; CPR = cefrozil; CAZ = ceftazidine; CRO = ceftriaxone; C = chloramphenicol; CIP = ciprofloxacine; E = erythromycin; FOS = fosfomycin; CN = gentamycin; IMP = imipenem; K = kanamycin; MEM = meropenem; NET = nethilmycin; OFX = ofloxacin; FEP = sefepime; VA = vancomycin.
Please cite this article in press as: Radji M, et al. Antibiotic therapy for diabetic foot infections in a tertiary care hospital in Jakarta, Indonesia. Diab Met Syndr: Clin Res Rev (2014), http://dx.doi.org/10.1016/j.dsx.2014.09.006
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DSX-429; No. of Pages 4 M. Radji et al. / Diabetes & Metabolic Syndrome: Clinical Research & Reviews xxx (2014) xxx–xxx
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frequency and duration of therapy. Pharmacists also play a role in monitoring the efficacy and safety of administering antibiotics in patients [32]. 5. Conclusion It can be concluded that diabetic foot infections (62.8%) were polymicrobial infections. S. aureus was most commonly found in the foot infections. Most of the microorganisms isolated from diabetic foot infections were resistant to many types of antibiotics. Conflict of interest We declare that we have no conflict of interest. References [1] International Diabetes Federation. IDF diabetes atlas. 6th edn. Brussels, Belgium: International Diabetes Federation; 2013, http://www.idf.org/diabetesatlas. [2] Pendsey SP. Understanding diabetic foot. Int J Diabetes Dev Ctries 2010;30:75–9. [3] Khanolkar MP, Bain SC, Stephens JW. The diabetic foot. QJM 2008;101:685–95. [4] Lipsky BA, Berendt AR, Cornia PB, Pile JC, Peters EJG, Armstrong DG, et al. Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis 2012;54:e132–73. [5] Citron DM, Goldstein EJC, Merriam CV, Lipsky BA, Abramson MA. Bacteriology of moderate-to-severe diabetic foot infections and in vitro activity of antimicrobial agents. J Clin Microbiol 2007;45:2819–28. [6] Gadepalli R, Dhawan B, Sreenivas V, Kapil A, Ammini AC, Chaudhry R. A clinicomicrobiological study of diabetic foot ulcers in an Indian tertiary care hospital. Diabetes Care 2006;29:1727–32. [7] Hefni AAH, Ibrahim AMR, Attia KM, Moawad MM, El-ramah AF, Shahin MM, et al. Bacteriological study of diabetic foot infection in Egypt. J Arab Soc Med Res 2013;8:26–32. [8] Lipsky BA. Empirical therapy for diabetic foot infections: are there clinical clues to guide antibiotic selection? Clin Microbiol Infect 2007;13:351–3. [9] Bader MS. Diabetic foot infection. Am Fam Physician 2008;78:71–9. [10] Shah SF, Hameed S, Khawaja Z, Abdullah T, Waqar SH, Zahid MA. Evaluation and management of diabetic foot: a multicenter study conducted at Rawalpindi, Islamabad. Ann Pak Inst Med Sci 2011;7(4):233–7. [11] Zgonis T, Stapleton JJ, Roukis TS. A stepwise approach to the surgical management of severe diabetic foot infections. Foot Ankle Spec 2008;1:46–53. [12] Clemens MW, Attinger CE. Functional reconstruction of the diabetic foot. Semin Plast Surg 2010;24:43–56.
[13] Singh S, Pai DR, Yuhhui C. Diabetic foot ulcer – diagnosis and management. Clin Res Foot Ankle 2013;1:120. http://dx.doi.org/10.4172/2329-910X. 1000120. [14] Ereshefsky B, Martin C. Antimicrobial management of foot infections in patients with diabetes mellitus. Orthopedics 2010;33(12):897–901. [15] Clayton Jr W, Elasy TA. A review of the pathophysiology, classification, and treatment of foot ulcers in diabetic patients. Clin Diabetes 2009;27:52–8. [16] Meggitt B. Surgical management of the diabetic foot. Br J Hosp Med 1976;16:227–332. [17] Wagner FW. The dysvascular foot: a system for diagnosis and treatment. Foot Ankle 1981;2:64–122. [18] Clinical and Laboratory Standard Institute (CLSI). Performance standards for antimicrobial susceptibility: sixteenth informational supplement. Wayne, PA, USA: CLSI; 2006, M100-S16. [19] Mendes JJ, Neves J. Diabetic foot infections: current diagnosis and treatment. J Diabet Foot Complicat 2012;4(2):26–45. [20] Gul A, Basit A, Ali SM, Ahmadani MY, Miyan Z. Role of wound classification in predicting the outcome of diabetic foot ulcer. J Pak Med Assoc 2006;56:444–7. [21] Mathangi T, Prabhakaran P. Prevalence of bacteria isolated from type 2 diabetic foot ulcers and the antibiotic susceptibility pattern. Int J Curr Microbiol Appl Sci 2013;2(10):329–37. [22] Alavi SM, Khosravi AD, Sarami A, Dashtebozorg A, Montazeri EA. Bacteriologic study of diabetic foot ulcer. Pak J Med Sci 2007;23:681–4. [23] Khoharo HK, Ansari S, Qureshi F. Diabetic foot ulcers. Prof Med J 2009;16: 53–60. [24] Sotto A, Lina G, Richard JL, Combescure C, Bourg G, Vidal L, et al. Virulence potential of Staphylococcus aureus strains isolated from diabetic foot ulcers: a new paradigm. Diabetes Care 2008;31:2318–24. [25] Santoso M, Yuliana M, Mujono W, Kusdiantomo. Pattern of diabetic foot at Koja Regional General Hospital, Jakarta, from 1999 to 2004. Acta Med Indones 2005;37:187–9. [26] Raja NS. Microbiology of diabetic foot infections in a teaching hospital in Malaysia: a retrospective study of 194 cases. J Microbiol Immunol Infect 2007;40:39–44. [27] Dowd SE, Sun Y, Secor PR, Rhoads DD, Wolcott BM, James GA, et al. Survey of bacterial diversity in chronic wounds using pyrosequencing, DGGE, and full ribosome shotgun sequencing. BMC Microbiol 2008;8:43–58. [28] Frykberg RG, Zgonis T, Armstrong DG, Driver VR, Giurini JM, Kravitz SR, et al. Diabetic foot disorders: a clinical practice guideline. J Foot Ankle Surg 2006;25(5):S1–66. [29] Fincke BG, Miller DR, Christiansen CL, Turpin RS. Variation in antibiotic treatment for diabetic patients with serious foot infections: a retrospective observational study. BMC Health Serv Res 2010;10:193. [30] Richard JL, Sotto A, Lavigne JP. New insights in diabetic foot infection. World J Diabetes 2011;2:24–32. [31] Lipsky BA, Hoey C. Topical antimicrobial therapy for treating chronic wounds. Clin Infect Dis 2009;49:1541–9. [32] Chahine EB, Harris S, Williams IIR. Diabetic foot infections: an update on treatment. US Pharm 2013;38(4):23–6.
Please cite this article in press as: Radji M, et al. Antibiotic therapy for diabetic foot infections in a tertiary care hospital in Jakarta, Indonesia. Diab Met Syndr: Clin Res Rev (2014), http://dx.doi.org/10.1016/j.dsx.2014.09.006
DSX-429; No. of Pages 4 Diabetes & Metabolic Syndrome: Clinical Research & Reviews xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Diabetes & Metabolic Syndrome: Clinical Research & Reviews journal homepage: www.elsevier.com/locate/dsx
Original Article
Antibiotic therapy for diabetic foot infections in a tertiary care hospital in Jakarta, Indonesia Maksum Radji a,*, Corry Shirleyana Putri a, Siti Fauziyah b a b
Laboratory of Microbiology and Biotechnology, Faculty of Pharmacy, University of Indonesia, Depok 16424, Indonesia Department of Pharmacy, Dr. Mintohardjo Navy Hospital, Bendungan Hilir No. 17, Jakarta 10210, Indonesia
A R T I C L E I N F O
A B S T R A C T
Keywords: Diabetic foot infections Antibiotic Clinical pharmacy Indonesia
Aims: The purpose of this study was to determine the microbiology of diabetic foot infections and to assess the antibiotic susceptibility patterns. Materials and methods: A cross sectional retrospective study of 35 patients with diabetic foot infections hospitalized at the internal medicine clinic of Dr. Mintohardjo Navy Hospital, Jakarta. The data were collected from patient medical records retrospectively. The classification of the diabetic foot infections was evaluated according to Meggit–Wagner’s Classification. Identification of causative microorganisms was performed by standard microbiologic methods. Antibiotic susceptibility testing was performed using disk-diffusion method. Results: During January to December 2012, a total of 288 of diabetic patients were admitted to hospital, and 35 patients had diabetic foot infections. According to Meggit–Wagner’s classification the most common disease was grade 3 in 31.4% patients, followed by grade 2 in 25.7%, and grade 4 in 17.3% of patients. Conservative diabetic control care was carried out in 37.1% of patients, and surgical intervention was carried out in 62.9% of patients. A total of 59 pathogens were identified. The most common infecting microorganism isolated on pus cultures was Staphylococcus aureus (47.5%), followed by Pseudomonas spp (16.9%), E. coli (10.2%), Streptococcus spp. (8.5%), Enterobacter spp. (7.0%), Proteus spp. (6.7%), and Acinetobacter spp. (3.2%). Overall, 37.2% of the diabetic foot infection caused by a single microorganism, and 62.8% had polymicrobial infections. The most frequently administrated antibiotic was ceftriaxone (40.0%), followed by ciprofloxacin (11.4%), and meropenem (8.6%). Conclusion: Diabetic foot infections (62.8%) were polymicrobial. S. aureus was most commonly found in the foot infection. Most of the microorganisms isolated from diabetic foot infection were resistant to many types of antibiotics. ß 2014 Diabetes India. Published by Elsevier Ltd. All rights reserved.
1. Introduction Diabetes mellitus is a serious and complex illness that affects almost all the vital organs in the body. Approximately 382 million people worldwide suffer from diabetes and it has been estimated that it will increase to 592 million by 2035. In 2013, diabetes caused more than 5.1 million deaths, where every 6 s a person dies from diabetes [1]. The disease is known to have many complications and one of the most severe is diabetic foot infection that affects 15% of people with diabetes, and leading to amputation [2]. Every year, more than one million diabetes patients require limb amputation [3].
* Corresponding author. E-mail address: [email protected] (M. Radji).
Indonesia is the seventh largest country in the case of diabetes mellitus incidence in the world after China, India, USA, Brazil, Russia and Mexico. The incidence of diabetes mellitus in Indonesia is estimated at about 8.5 million in 2013 [1]. For the treatment of diabetes mellitus, the Infectious Diseases Society of America (IDSA) has recommended a guideline that the treatment of diabetic foot infection should be performed by a team of multidisciplinary diabetic foot care consisting of an infectious disease specialist, specialist of clinical microbiology, foot surgeons, and wound-care specialists [4]. Diabetic foot infections are often caused by a number of infecting microorganisms. Staphylococcus aureus, Streptococcus pyogenes, Staphylococcus epidermidis, E. coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter spp, Proteus spp., and Enterococcus spp. are some of the frequent pathogens contribute to progressive tissue damage [4–7]. The presence of obligate anaerobes associated with
http://dx.doi.org/10.1016/j.dsx.2014.09.006 1871-4021/ß 2014 Diabetes India. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Radji M, et al. Antibiotic therapy for diabetic foot infections in a tertiary care hospital in Jakarta, Indonesia. Diab Met Syndr: Clin Res Rev (2014), http://dx.doi.org/10.1016/j.dsx.2014.09.006
G Model
DSX-429; No. of Pages 4 M. Radji et al. / Diabetes & Metabolic Syndrome: Clinical Research & Reviews xxx (2014) xxx–xxx
2
necrosis, gangrene, or ischemic tissue and usually occurs in severe chronic infections [4,8,9]. Diabetic foot infections caused by bacteria such as multi-drug-resistant methicillin-resistant S. aureus usually occurs in patients who are admitted to the hospital and in the community with a high prevalence of drug resistance [4,8,9]. The increasing of diabetic foot infections caused by multidrugresistant pathogen is responsible for the duration of hospitalization, morbidity and mortality of diabetic patients [6]. The optimal treatment of diabetic foot infection is still a matter of concern. This diabetic complication is very difficult to treat if proper protocol is not followed [10–12]. However, most researchers agree that the management of this infection requires isolation and identification of microbial flora, appropriate antibiotic therapy according to the local sensitivity pattern, proper selection and identification of chronic complications and appropriate surgical intervention for this complication [7]. Educating diabetic patients is one of another way in preventing diabetic foot infections and to improve the outcomes of therapy. Empirical broad-spectrum antibiotic regimens can be administrated. However, the sensitivity tests of bacterial pathogens should be performed to assist in the selection of appropriate antibiotic treatment regimens [13]. Narrow-spectrum antibiotics can be selected for acute or less severe infection, while the broadspectrum antibiotics should be used in cases of chronic or severe infection [14]. The appropriate diabetic foot infections care could prevent more than 40% of amputations [15]. In Indonesia, there has been a limited study of the diabetic foot infections care, especially the control of infection by appropriate antibiotics. Therefore, the purpose of this study was to evaluate the antibiotic treatment for diabetic foot infection in Dr. Mintohardjo Navy Hospital, Jakarta Indonesia.
2. Patients and methods A retrospective cross-sectional study was carried out at tertiary care Navy Hospital of Dr Mintohardjo, Jakarta, Indonesia. Demographic and clinical data were collected retrospectively from patient medical records who had admitted to hospital during January to December 2012. The inclusion criteria were inpatients that hospitalized at internal medicine clinic, suffered diabetic foot infection. Out patients and patients with incomplete information of medical records were excluded from the study. The classification of the diabetic foot infections were evaluated according to Meggit– Wagner’s Classification [16,17]. 2.1. Isolation of bacteria and antibiotic susceptibility test All foot ulcer samples were collected aseptically and were plated right after the collection. Identification of causative microorganisms was performed by standard microbiologic methods. Antibiotic susceptibility testing was performed using diskdiffusion method. The results were interpreted according to the guidelines of the Clinical and Laboratory Standards Institute [18].
27.80%
5.60%
16.70% 4 40-50 years 5 51-60 years 6 61-70 years 49.80
> 70 years
Fig. 1. The age range of diabetic foot patients.
3. Results During January to December 2012, a total of 288 of diabetic patients were admitted to hospital, of which 35 diabetic foot infection patients were hospitalized and have been considered as qualified for inclusion criteria. We found that diabetic foot infection affected males slightly more frequent (54.3%) as compared to females (45.7%); the male to female ratio was 1.18:1. The age ranged of diabetic foot patients was from 46 to 75 years, and the most common age groups of diabetic foot patients was the age group of 51–60 years, followed by the 61–70 years age group as shown in Fig. 1. The grade of diabetic foot infection according to Meggit–Wagner’s classification is shown in Table 1. The commonest disease was grade 3 that comprised of 31.4% patients, followed by grade 2 in 25.7%, and grade 4 in 17.3% of patients. Conservative diabetic control care was carried out in 37.1% patients and surgical intervention was carried out in 62.9% of patients. We found that the most of the diabetic foot patients were hospitalized for 6–10 days as shown in Fig. 2. A total of 59 pathogens were identified with an average of 1.68 microorganisms per patient. The most common infecting microorganism isolated on pus cultures was S. aureus (47.5%), followed by Pseudomonas spp (16.9%), E. coli (10.2%), Streptococcus spp. (8.5%), Enterobacter spp. (7.0%), Proteus spp. (6.7%), and Acinetobacter spp. (3.2%). Overall, 37.2% of the cultures were a single microorganism, and 62.8% had mixed infections. The results of sensitivity patterns of the isolated microorganisms are shown in Table 2.
4. Discussion Diabetes mellitus is a global health problem which diabetic foot infection is one of the most serious complications [19]. This complication is more common in the older age group compared with younger ones. In our study we found that the most commonly affected age group was between 50 and 60 years. This result was similar to previous studies that diabetic foot infections often occur in patients older than 50 years [7,10,20]. Various studies show that diabetic foot infection has the longest hospital stay as compared to other complications of diabetes
Table 1 The grade frequency of diabetic foot infection according to the Meggit–Wagner’s Classification of Diabetic Foot infections. Grade
Disease
Treatment management
Frequency (%)
0 1 2
No ulcer in a risk foot Superficial ulcer Deep ulcer, involve ligaments and muscles, but no bone involvement Deep ulcer with bone involvement often with osteomyelitis Localized gangrene Extensive gangrene of the whole foot
Prevention Antibiotics, glycemic control, and local wound care Antibiotics and glycemic control, adequate perfusion, local wound care and regular debridement Antibiotics and glycemic control, debridements, and off-loading of the foot Extensive debridement with or without amputation Amputation
0 11.4 25.7
3 4 5
31.4 17.3 14.2
Please cite this article in press as: Radji M, et al. Antibiotic therapy for diabetic foot infections in a tertiary care hospital in Jakarta, Indonesia. Diab Met Syndr: Clin Res Rev (2014), http://dx.doi.org/10.1016/j.dsx.2014.09.006
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Fig. 2. The duration of hospitalization of diabetic foot infection patients.
[11,12]. We found that the most of the diabetic foot patients were hospitalized for about 2 weeks. However some patients were hospitalized more than 4 weeks. Approximately one third of patients (37.1%) were managed conservatively while the remaining patients were managed by surgical intervention, including wound dressing, debridement and extensive debridement in 46.2% and amputation in (16.7%). The commonest microorganism isolated on pus cultures was S. aureus (47.5%). This result was similar to some other studies that S. aureus is the most common bacteria isolated from the cultures of diabetic foot infections [4,9,21–24]. However our results were in contrast to previous local study conducted at Koja Regional General Hospital, Jakarta that P. aeruginosa was the most frequent bacteria isolated form diabetic foot infections [25]. Our findings showed that 62% of patients were infected by two or more pathogens. This result was consistent to other studies that most diabetic foot infections are generally a poly-microbial infection. Mixed pathogens commonly found in wound infections [5,7,26,27]. In this study, the most frequent administrated antibiotic was ceftriaxone (40.0%), followed by ciprofloxacin (11.4%), and meropenem (8.6%). However, all infecting bacteria had showed low sensitivity against ceftriaxone. Regarding to the susceptibility patterns, we found that about 10% of Staphylococcus were MRSA as shown in Table 2. Most of the isolated bacteria showed resistance against some antibiotics and therefore, we assumed that monotherapy might not be the best management for therapy of diabetic foot infection. The increasing incidence of multi-drug resistant organisms is a potential risk factor in management of diabetic foot infections. The local pattern of bacterial etiology and their susceptibility is very important in choosing empirical antibiotic therapy for diabetic foot infections. In term of antibiotic therapy, the guidelines of antimicrobials management for diabetic foot infections have been established
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worldwide [4,14,28]. However, these guidelines have not been fully used in the treatment of diabetic foot infections [29]. Generally, empirical antibiotic treatment can be administrated for diabetic foot infections according to the severity of infection. Narrow-spectrum antibiotics may be given in cases of acute or less severe infections, while the broad-spectrum antibiotics should be used parenterally in cases of chronic or severe infections [14]. In mild infections of outpatients should not be treated with topical or systemic antibiotics, and should be treated with oral antibiotics for 1–2 weeks [4]. S. aureus and beta-hemolytic Streptococcus are the most common bacteria found in patients with mild to moderate diabetic foot infection [4,8,9,14]. For mild infections could use oral antibiotics such as cephalexin, amoxicillin/clavulanate, levofloxacin or dicloxacillin, and antibiotics that cover methicillin resistant S. aureus (MRSA) include clindamycin, doxycycline, and timethoprim/sulfamethoxazole [4,14]. For moderate infections can be treated initially with oral antibiotics or with parenteral antibiotics, followed by oral therapy for 1–3 weeks. Whereas severe infections requiring hospitalization and treatment with parenteral antibiotics followed by oral therapy, for 2–4 weeks [4]. Some potential broad-spectrum antibiotic for use in diabetic foot infections such as Piperacillin/tazobactam, meropenem, doripenem, ertapenem, aztreonam, levofloxacin, ciprofloxacin, ceftriaxone, clindamycin, vancomycin, daptomycin, linezolid, imipenem, and tigecycline [4,14]. Piperacillin/tazobactam, doripenem and meropenem have been shown to have excellent activity against the majority of bacterial isolates from diabetic foot infection including P. aeruginosa [14]. Other consideration in the treatment of diabetic foot infection is the use of topical antibiotics. Although current use of topical antibiotics is not recommended especially for patients infected chronic wounds, but may have a role in certain conditions [19,30]. Topical antibiotics should always be preceded by debridement and can be considered to be given to subclinical infection or to assist in removing bacterial biofilms, which have led to persistent wound infection [31]. Diabetic foot infection is one of some complication of diabetes that is very difficult to overcome, and therefore the management of diabetic foot infection should be performed by a multidisciplinary approach [4,19,32]. Pharmacists, as the most accessible health care professional has a central role in helping to prevent diabetic foot infections. Pharmacists should play a role in empowering and educating patients with diabetes to maintain optimal blood glucose levels and monitor medication adherence of patient. In addition pharmacists should be involved with other health care professionals to choose the most appropriate antimicrobial regimen for the patient, including dosage, route of administration,
Table 2 Sensitivity patterns of isolated microorganisms. Microorganism
Antibiotic sensitivity pattern (%) AMP
AK
CFP
CTX
CPR
CAZ
CRO
C
CIP
E
FOS
CN
IMP
K
MEM
NET
OFX
FEP
VA
Streptococcus spp S. aureus MRSA Peudomonas spp E. coli Proteus spp Enterobacter spp Acinetobacter spp
100
100
70
50
80
70
40
100
90
70
90
100
100
70
100
90
100
100
100
100 0 10
100 0 70
60 0 10
80 0 20
70 0 10
60 0 30
50 0 10
90 40 30
70 0 60
60 0 40
80 30 70
90 0 60
100 20 80
60 0 70
100 20 90
80 0 80
80 40 80
100 0 80
100 100 0
60 30 10
80 70 30
60 60 20
70 50 40
70 40 50
80 70 50
60 60 40
100 90 80
90 60 40
70 70 30
70 70 70
50 80 70
100 80 70
60 50 40
100 80 60
80 70 30
100 80 60
90 80 70
20 10 20
10
60
40
50
60
30
40
70
40
60
80
50
40
50
40
60
40
50
10
AMP = ampicillin; AK = amikacin; CFP = cefoperazon; CTX = cefotaxime; CPR = cefrozil; CAZ = ceftazidine; CRO = ceftriaxone; C = chloramphenicol; CIP = ciprofloxacine; E = erythromycin; FOS = fosfomycin; CN = gentamycin; IMP = imipenem; K = kanamycin; MEM = meropenem; NET = nethilmycin; OFX = ofloxacin; FEP = sefepime; VA = vancomycin.
Please cite this article in press as: Radji M, et al. Antibiotic therapy for diabetic foot infections in a tertiary care hospital in Jakarta, Indonesia. Diab Met Syndr: Clin Res Rev (2014), http://dx.doi.org/10.1016/j.dsx.2014.09.006
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DSX-429; No. of Pages 4 M. Radji et al. / Diabetes & Metabolic Syndrome: Clinical Research & Reviews xxx (2014) xxx–xxx
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frequency and duration of therapy. Pharmacists also play a role in monitoring the efficacy and safety of administering antibiotics in patients [32]. 5. Conclusion It can be concluded that diabetic foot infections (62.8%) were polymicrobial infections. S. aureus was most commonly found in the foot infections. Most of the microorganisms isolated from diabetic foot infections were resistant to many types of antibiotics. Conflict of interest We declare that we have no conflict of interest. References [1] International Diabetes Federation. IDF diabetes atlas. 6th edn. Brussels, Belgium: International Diabetes Federation; 2013, http://www.idf.org/diabetesatlas. [2] Pendsey SP. Understanding diabetic foot. Int J Diabetes Dev Ctries 2010;30:75–9. [3] Khanolkar MP, Bain SC, Stephens JW. The diabetic foot. QJM 2008;101:685–95. [4] Lipsky BA, Berendt AR, Cornia PB, Pile JC, Peters EJG, Armstrong DG, et al. Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis 2012;54:e132–73. [5] Citron DM, Goldstein EJC, Merriam CV, Lipsky BA, Abramson MA. Bacteriology of moderate-to-severe diabetic foot infections and in vitro activity of antimicrobial agents. J Clin Microbiol 2007;45:2819–28. [6] Gadepalli R, Dhawan B, Sreenivas V, Kapil A, Ammini AC, Chaudhry R. A clinicomicrobiological study of diabetic foot ulcers in an Indian tertiary care hospital. Diabetes Care 2006;29:1727–32. [7] Hefni AAH, Ibrahim AMR, Attia KM, Moawad MM, El-ramah AF, Shahin MM, et al. Bacteriological study of diabetic foot infection in Egypt. J Arab Soc Med Res 2013;8:26–32. [8] Lipsky BA. Empirical therapy for diabetic foot infections: are there clinical clues to guide antibiotic selection? Clin Microbiol Infect 2007;13:351–3. [9] Bader MS. Diabetic foot infection. Am Fam Physician 2008;78:71–9. [10] Shah SF, Hameed S, Khawaja Z, Abdullah T, Waqar SH, Zahid MA. Evaluation and management of diabetic foot: a multicenter study conducted at Rawalpindi, Islamabad. Ann Pak Inst Med Sci 2011;7(4):233–7. [11] Zgonis T, Stapleton JJ, Roukis TS. A stepwise approach to the surgical management of severe diabetic foot infections. Foot Ankle Spec 2008;1:46–53. [12] Clemens MW, Attinger CE. Functional reconstruction of the diabetic foot. Semin Plast Surg 2010;24:43–56.
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Please cite this article in press as: Radji M, et al. Antibiotic therapy for diabetic foot infections in a tertiary care hospital in Jakarta, Indonesia. Diab Met Syndr: Clin Res Rev (2014), http://dx.doi.org/10.1016/j.dsx.2014.09.006
