of 100 Consecutive Diabetic Foot Infections and In Vitro Susceptibility to
Bacteriology
Ampicillin/Sulbactam Versus
Cefoxitin
Edgar Borrero, M.D., F.A.C.A., F.I.C.A.,
F.I.C.S.
and Michael Rossini, Jr., M.D.
BALTIMORE, MARYLAND
Abstract
complications of diabetes mellitus is the occurrence of infection. The polymicrobial nature of diabetic foot infection has
One of the major
diabetic foot been well documented in the literature. In order to avoid amputation of the tissue affected, the ulceration and infection must be appropriately diagnosed and treated. This paper describes the microbiologic and clinical features obtained from 100 consecutive diabetic infected foot patients treated with either cefoxitin or ampicillin/sulbactam. Introduction
Severe diabetic foot infections are polymicrobial infections. 1-7 The management of the infection requires appropriate deep-tissue cultures, timely debridement, and broad-spectrum antibiotic therapy, as needed, to salvage the infected limb. Numerous parenteral antibiotics have been used over the years to eradicate the infection. At the time of this study, cefoxitin was widely used to treat these diabetic foot infections with mixed results. With the advent of newer, broad-spectrum antibiotics, such as ampicillin/sulbactam, more antimicrobial coverage can be obtained. The advantages of utilizing a broader spectrum antibiotic include (1) decreased need for addition of a second or third antibiotic, thereby containing cost; (2) avoidance of nephrotoxic, ototoxic, or hepatotoxic antibiotics; (3) reduction of time needed for the nursing staff to administer one antibiotic as opposed to two or more; and (4) decreased risk of adverse drug reactions.
From the
Department of Surgery,
Division of Vascular
Surgery, Baltimore, Maryland
357
Downloaded from ang.sagepub.com at UCSF LIBRARY & CKM on March 21, 2015
358 Materials and Methods One hundred diabetic patients with infected foot ulcers were admitted to the vascular surgery service from July 1, 1987, to November, 1988. Immediately after admission, deep-tissue cultures of the infected ulcer were obtained from all patients. Cultures were rapidly transported to the microbiology laboratory. For aerobic and microaerophilic cultures, 5 % sheep blood agar, MacConkey agar, Columbia colistin-nalidixic acid agar, and chocolate agar plates were used. Brucella blood agar with 10 gg of menadione/mL, phenylethyl alcohol-blood agar, and laked-blood agar with 75 mg of kanamycin/mL plus 7.5 ~g of vancomycin/mL were used for anaerobic cultures. Enterobacteriaceae were identified by the methods of Edwards and Ewing,g and nonfermentative bacilli, by the method of Pickett and Pedersen.9 Anaerobic bacteria were identified according to the procedures outlined in Virginia Polytechnic Institutes’ Anaerobe Laboratory Manual.’o Gas-liquid chromatographic studies of anaerobic bacteria were performed according to the criteria of the Virginia Polytechnic Institute. Resistance was determined by the disc assay method.
Results The clinical characteristics of the 100 consecutive patients studied are shown in Table I. In general, the patients were elderly, had been insulin dependent for several years, and demonstrated evidence of peripheral neuropathy. The vast majority had had the infected foot ulcer for more than one month. Approximately one third of the patients had had limb loss (above- or below-knee amputation). A total of 505 isolates (301 aerobes and 204 anaerobes) were recovered from the deeptissue cultures in the 100 patients studied (Table II and III): cultures for 10 patients yielded TABLE I General Clinical Features of 100 Consecutive Diabetic Patients with Infected Foot Ulcers
Downloaded from ang.sagepub.com at UCSF LIBRARY & CKM on March 21, 2015
.
359 for 1, only anaerobes; and for 89, mixed aerobes and anaerobes. On average, 5 bacterial isolates per specimen with an average of 3 aerobes and 2 anaerobes per deep-tissue culture were recovered. There were 98 aerobes (45 Group D Streptococcus, 2 Staph. aureus, 15 Enterobacter, 3 E. coli, 10 coagulase-negative staphylococci, 2 Klebsiella, 8 Proteus, 2 Providencia, 9 Pseudomonas, 2 Serratia) and 67 anaerobes resistant to cefoxitin. In comparison, there were only 20 aerobes (2 microaerophilic streptococci, 2 corynebacteria, 1 Enterobacter, 1 Klebsiella, 2 Proteus, 1 Providencia, 9 Pseudomonas, 2 Serratia) and 5 anaerobes resistant to ampicillin/ sulbactam. All of the Group D streptococci (enterococci) were resistant to cefoxitin and sensitive to ampicillin/sulbactam. The relationship of clinical features to deep-tissue microbiology was as follows: the total number of isolates; the number of aerobic or anaerobic isolates; the density of growth of aerobes, anaerobes, or combined aerobes and anaerobes; and the presence or absence of anaerobes did not differ significantly between these patients with, respectively (1) duration of foot infection less than one month or greater than one month, (2) insulin dependence and noninsulin dependence, (3) presence or absence of gas in soft tissue (by physical or radiologic examination), (4) presence or absence of osteomyelitis (by roentgenogram), (5) presence or absence of peripheral leukocytosis (WBC count > 10,000/mm), or (6) presence or absence of a fever (oral temperature > 101 ° F) .
only aerobes;
TABLE II Aerobic Microorganisms Isolated from the Deep-Tissue Cultures of 100 Diabetic Patients with Infected Feet
TABLE III Anaerobic Bacteria Isolated from the Deep-7-issue Diabetic Patients with Infected Feet
Downloaded from ang.sagepub.com at UCSF LIBRARY & CKM on March 21, 2015
of 100
360
Sixty patients had foul-smelling lesions and all 60 patients’ ulcers yielded anaerobes on deep-tissue culture. All patients received iodophor or sodium hypochlorate wet to dry dressings to open ulcers during their hospitalization. There was no significant difference, in terms of limb salvage, between the two groups.
Discussion The polymicrobial nature of foot infections in the diabetic patient is again documented in this report. This is, however, the first report comparing the sensitivity of the bacteria cultured from infected diabetic feet to ampicillin/sulbactam and cefoxitin. Ampicillin/sulbactam is a new broad-spectrum beta-lactamase-inhibiting antiobiotic. This unique antibiotic has been used for severe, polymicrobial intraabdominal and gynecological infections with excellent results. Because of the excellent results reported in treating peritoneal infections, we wanted to determine whether it would be appropriate for treating diabetic foot infections. The microorganisms most frequently isolated in this study were Bacteroides, gram-negative enteric bacilli, group D Streptococcus, anaerobic streptococci, and Clostridia. The majority of the anaerobes were Bacteroides (7 different species being isolated). Among the gram-negative enteri bacilli, Proteus mirabiis was the most frequently seen, followed by E. coli, Proteus vulgaris, and Klebsiella. Of the 67 isolates of gram-positive anaerobic cocci, Peptococcus magnus was the most frequently seen. The mainstay of treatment of the infected diabetic foot is appropriate debridement and drainage combined with broad-spectrum parenteral antibiotic therapy.1l,12 Monotherapy has been advocated because of its ease of administration (ie, pharmacy preparation and nursing administration time), lower cost, and increased safety. Avoidance of aminoglycoside antibiotics in diabetic patients with cardiovascular disease has also been advocated to avoid nephrotoxicity (especially in patients requiring an arteriogram). 13 We try to avoid the use of aminoglycoside antibiotics in our diabetic patients, when feasible. In the past, anaerobes have frequently been overlooked in the antibiotic management of the infected diabetic foot. With improved culture techniques, however, anaerobic bacteria have been found to play a major role in a large number of human infections, especially in the diabetic. The vast majority of infections in which anaerobics play a role are polymicrobial. Use of aminoglycosides may predispose to anaerobic superinfection because they are typically inactive against these organisms.’4 This is also true for monotherapy with an antibiotic that has minimal activity against anaerobes or an antibiotic to which anaerobes have developed resistance.
experiencing increasing resistance to cefoxitin. Clinically, an increasing number of patients with persistent infections due to anaerobic &dquo;superinfections&dquo; were seen. When ampicillin/sulbactam was used, no persistent anaerobic infections were evident clinically. Persistent infection in the diabetic foot may also be due to group D Streptococcus (Enterococcus). The majority of patients who develop enterococcal superinfections have received a cephalosporin.’S Gibbons and Eliopoulos state: &dquo;in the patient with progressive infection deAt
our
institution,
we were
Downloaded from ang.sagepub.com at UCSF LIBRARY & CKM on March 21, 2015
361
spite an extended course of therapy with a cephalosporin, organisms such as enterococci and Ps. aeruginosa may predominate.,,13 In a study of 30 patients with diabetic foot infections by Fierer et al, 6 patients (20%) had persistent enterococcal infection after cofoxitin therapy, requiring amputation above the ankle level . In a study of 75 patients with enterococcal bacteremia, Gullberg et al state that &dquo;enterococcal bacteremia, commonly acquired nosocomially, can lead to significant morbidity and death&dquo; (30% of the patients died in the hospital).’6 The widespread use of cephalosporin antibiotics presumably is a predisposing factor.’6 In our study, all of the group D streptococci (enterococci) were resistant to cefoxitin as opposed to all 45 group D streptococci, which were sensitive to ampicillin/sulbactam. 4
Conclusions Diabetic foot infections should be treated as limb-threatening infections requiring emergency admission and immediate attention. Early and aggressive surgical debridement of necrotic, infected tissues and drainage of purulent collections is crucial for limb salvage. In addition, therapeutic parenteral antimicrobial therapy must be instituted immediately. When choosing an antimicrobial for the treatment of diabetic foot infections, one should consider, not only the spectrum of causative organisms and their resistance patterns, but also the efficacy, safety, and cost of therapy. Ampicillin/sulbactam has excellent broad-spectrum coverage and is the antibiotic of choice for treatment of diabetic foot infections in patients who do not have a penicillin allergy.
Edgar Borrero, M.D., FACA, FICA, Good Samaritan Hospital 786 Montauk Highway West Islip, NY 11795
FICS
References 1. Pratt TC: Gangrene and infection in the diabetic. Med Clin North Am 49:987-1004, 1965. 2. Sharp CS, Bessman AN, Wagner FW Jr, et al: Microbiology of deep tissue in diabetic gangrene. Diabetes Care 1:289-292, 1978. 3. Louie TJ, Bartlett JG, Tally FP, et al: Aerobic and anaerobic bacteria in diabetic foot ulcers. Ann Int Med 85:461-463, 1976. 4. Fierer J, Daniel D, Davis C: The fetid foot; lower extremity infections in patients with diabetes mellitus. Rev Infect Dis 1:210-217, 1979. 5. Sharp CS, Bessman AN, Wagner FW Jr, et al: Microbiology of superficial and deep tissues in infected diabetic gangrene. Surg Gynecol Obstet 149:217-219, 1979. 6. Sapico FL, Witte JL, Canawati HN, et al: The infected foot of the diabetic patient: Quantitative microbiology and analysis of clinical features. Rev Infect Dis 6:S171-S176, 1984. 7. Towne JB: Management of foot lesions in the diabetic patient. In: Vascular Surgery. Philadephia; WB Saunders Co, 1984, pp 661-669 8. Edwards PR, Ewing WH: Identification of Enterobacteriaceae, ed. 3. Minneapolis: Burgess Publising Co,
1972 9. Pickett MJ, Pedersen MM: Nonfermentative bacilli associated in man. II. Detection and identification. Am J Clin Pathol 54:164-177, 1970. 10. Holdeman LV, Cato EP, Moore WEC: Anaerobe Laboratory Manual, ed. 4. Blacksburg, Va: Anaerobe Laboratory, Virginia Polytechnic Institute and State University, 1977. 11. Gibbons GW: The diabetic foot: Amputations and drainage of infection. J Vasc Surg 5:791-793, 1987. 12. Kahn O, Wagner W, Bessman A: Mortality of diabetic patients treated surgically for lower limb infection and/ or gangrene. Diabetes 23:287-292, 1974. 13. Gibbons GW, Eliopoulos GM: Infection of the diabetic foot. In: Management of Diabetic Foot Problems. Philadelphia : WB Saunders Co. 1984, pp 97-102. 14. Finegold SM: Anaerobic bacteria: Their role in infection and their management. Postgrad Med 81:141-147, 1987. 15. Mills J: Enterococcal superinfections. Infections in Surg, 1986 Special Supplement, pp 13-16. 16. Gullberg RM, Homann SR, Phair JP: Enterococcal bacteremia: Analysis of 75 episodes. Rev Infect Dis 11:74-85, 1989.
Downloaded from ang.sagepub.com at UCSF LIBRARY & CKM on March 21, 2015
Bacteriology
Ampicillin/Sulbactam Versus
Cefoxitin
Edgar Borrero, M.D., F.A.C.A., F.I.C.A.,
F.I.C.S.
and Michael Rossini, Jr., M.D.
BALTIMORE, MARYLAND
Abstract
complications of diabetes mellitus is the occurrence of infection. The polymicrobial nature of diabetic foot infection has
One of the major
diabetic foot been well documented in the literature. In order to avoid amputation of the tissue affected, the ulceration and infection must be appropriately diagnosed and treated. This paper describes the microbiologic and clinical features obtained from 100 consecutive diabetic infected foot patients treated with either cefoxitin or ampicillin/sulbactam. Introduction
Severe diabetic foot infections are polymicrobial infections. 1-7 The management of the infection requires appropriate deep-tissue cultures, timely debridement, and broad-spectrum antibiotic therapy, as needed, to salvage the infected limb. Numerous parenteral antibiotics have been used over the years to eradicate the infection. At the time of this study, cefoxitin was widely used to treat these diabetic foot infections with mixed results. With the advent of newer, broad-spectrum antibiotics, such as ampicillin/sulbactam, more antimicrobial coverage can be obtained. The advantages of utilizing a broader spectrum antibiotic include (1) decreased need for addition of a second or third antibiotic, thereby containing cost; (2) avoidance of nephrotoxic, ototoxic, or hepatotoxic antibiotics; (3) reduction of time needed for the nursing staff to administer one antibiotic as opposed to two or more; and (4) decreased risk of adverse drug reactions.
From the
Department of Surgery,
Division of Vascular
Surgery, Baltimore, Maryland
357
Downloaded from ang.sagepub.com at UCSF LIBRARY & CKM on March 21, 2015
358 Materials and Methods One hundred diabetic patients with infected foot ulcers were admitted to the vascular surgery service from July 1, 1987, to November, 1988. Immediately after admission, deep-tissue cultures of the infected ulcer were obtained from all patients. Cultures were rapidly transported to the microbiology laboratory. For aerobic and microaerophilic cultures, 5 % sheep blood agar, MacConkey agar, Columbia colistin-nalidixic acid agar, and chocolate agar plates were used. Brucella blood agar with 10 gg of menadione/mL, phenylethyl alcohol-blood agar, and laked-blood agar with 75 mg of kanamycin/mL plus 7.5 ~g of vancomycin/mL were used for anaerobic cultures. Enterobacteriaceae were identified by the methods of Edwards and Ewing,g and nonfermentative bacilli, by the method of Pickett and Pedersen.9 Anaerobic bacteria were identified according to the procedures outlined in Virginia Polytechnic Institutes’ Anaerobe Laboratory Manual.’o Gas-liquid chromatographic studies of anaerobic bacteria were performed according to the criteria of the Virginia Polytechnic Institute. Resistance was determined by the disc assay method.
Results The clinical characteristics of the 100 consecutive patients studied are shown in Table I. In general, the patients were elderly, had been insulin dependent for several years, and demonstrated evidence of peripheral neuropathy. The vast majority had had the infected foot ulcer for more than one month. Approximately one third of the patients had had limb loss (above- or below-knee amputation). A total of 505 isolates (301 aerobes and 204 anaerobes) were recovered from the deeptissue cultures in the 100 patients studied (Table II and III): cultures for 10 patients yielded TABLE I General Clinical Features of 100 Consecutive Diabetic Patients with Infected Foot Ulcers
Downloaded from ang.sagepub.com at UCSF LIBRARY & CKM on March 21, 2015
.
359 for 1, only anaerobes; and for 89, mixed aerobes and anaerobes. On average, 5 bacterial isolates per specimen with an average of 3 aerobes and 2 anaerobes per deep-tissue culture were recovered. There were 98 aerobes (45 Group D Streptococcus, 2 Staph. aureus, 15 Enterobacter, 3 E. coli, 10 coagulase-negative staphylococci, 2 Klebsiella, 8 Proteus, 2 Providencia, 9 Pseudomonas, 2 Serratia) and 67 anaerobes resistant to cefoxitin. In comparison, there were only 20 aerobes (2 microaerophilic streptococci, 2 corynebacteria, 1 Enterobacter, 1 Klebsiella, 2 Proteus, 1 Providencia, 9 Pseudomonas, 2 Serratia) and 5 anaerobes resistant to ampicillin/ sulbactam. All of the Group D streptococci (enterococci) were resistant to cefoxitin and sensitive to ampicillin/sulbactam. The relationship of clinical features to deep-tissue microbiology was as follows: the total number of isolates; the number of aerobic or anaerobic isolates; the density of growth of aerobes, anaerobes, or combined aerobes and anaerobes; and the presence or absence of anaerobes did not differ significantly between these patients with, respectively (1) duration of foot infection less than one month or greater than one month, (2) insulin dependence and noninsulin dependence, (3) presence or absence of gas in soft tissue (by physical or radiologic examination), (4) presence or absence of osteomyelitis (by roentgenogram), (5) presence or absence of peripheral leukocytosis (WBC count > 10,000/mm), or (6) presence or absence of a fever (oral temperature > 101 ° F) .
only aerobes;
TABLE II Aerobic Microorganisms Isolated from the Deep-Tissue Cultures of 100 Diabetic Patients with Infected Feet
TABLE III Anaerobic Bacteria Isolated from the Deep-7-issue Diabetic Patients with Infected Feet
Downloaded from ang.sagepub.com at UCSF LIBRARY & CKM on March 21, 2015
of 100
360
Sixty patients had foul-smelling lesions and all 60 patients’ ulcers yielded anaerobes on deep-tissue culture. All patients received iodophor or sodium hypochlorate wet to dry dressings to open ulcers during their hospitalization. There was no significant difference, in terms of limb salvage, between the two groups.
Discussion The polymicrobial nature of foot infections in the diabetic patient is again documented in this report. This is, however, the first report comparing the sensitivity of the bacteria cultured from infected diabetic feet to ampicillin/sulbactam and cefoxitin. Ampicillin/sulbactam is a new broad-spectrum beta-lactamase-inhibiting antiobiotic. This unique antibiotic has been used for severe, polymicrobial intraabdominal and gynecological infections with excellent results. Because of the excellent results reported in treating peritoneal infections, we wanted to determine whether it would be appropriate for treating diabetic foot infections. The microorganisms most frequently isolated in this study were Bacteroides, gram-negative enteric bacilli, group D Streptococcus, anaerobic streptococci, and Clostridia. The majority of the anaerobes were Bacteroides (7 different species being isolated). Among the gram-negative enteri bacilli, Proteus mirabiis was the most frequently seen, followed by E. coli, Proteus vulgaris, and Klebsiella. Of the 67 isolates of gram-positive anaerobic cocci, Peptococcus magnus was the most frequently seen. The mainstay of treatment of the infected diabetic foot is appropriate debridement and drainage combined with broad-spectrum parenteral antibiotic therapy.1l,12 Monotherapy has been advocated because of its ease of administration (ie, pharmacy preparation and nursing administration time), lower cost, and increased safety. Avoidance of aminoglycoside antibiotics in diabetic patients with cardiovascular disease has also been advocated to avoid nephrotoxicity (especially in patients requiring an arteriogram). 13 We try to avoid the use of aminoglycoside antibiotics in our diabetic patients, when feasible. In the past, anaerobes have frequently been overlooked in the antibiotic management of the infected diabetic foot. With improved culture techniques, however, anaerobic bacteria have been found to play a major role in a large number of human infections, especially in the diabetic. The vast majority of infections in which anaerobics play a role are polymicrobial. Use of aminoglycosides may predispose to anaerobic superinfection because they are typically inactive against these organisms.’4 This is also true for monotherapy with an antibiotic that has minimal activity against anaerobes or an antibiotic to which anaerobes have developed resistance.
experiencing increasing resistance to cefoxitin. Clinically, an increasing number of patients with persistent infections due to anaerobic &dquo;superinfections&dquo; were seen. When ampicillin/sulbactam was used, no persistent anaerobic infections were evident clinically. Persistent infection in the diabetic foot may also be due to group D Streptococcus (Enterococcus). The majority of patients who develop enterococcal superinfections have received a cephalosporin.’S Gibbons and Eliopoulos state: &dquo;in the patient with progressive infection deAt
our
institution,
we were
Downloaded from ang.sagepub.com at UCSF LIBRARY & CKM on March 21, 2015
361
spite an extended course of therapy with a cephalosporin, organisms such as enterococci and Ps. aeruginosa may predominate.,,13 In a study of 30 patients with diabetic foot infections by Fierer et al, 6 patients (20%) had persistent enterococcal infection after cofoxitin therapy, requiring amputation above the ankle level . In a study of 75 patients with enterococcal bacteremia, Gullberg et al state that &dquo;enterococcal bacteremia, commonly acquired nosocomially, can lead to significant morbidity and death&dquo; (30% of the patients died in the hospital).’6 The widespread use of cephalosporin antibiotics presumably is a predisposing factor.’6 In our study, all of the group D streptococci (enterococci) were resistant to cefoxitin as opposed to all 45 group D streptococci, which were sensitive to ampicillin/sulbactam. 4
Conclusions Diabetic foot infections should be treated as limb-threatening infections requiring emergency admission and immediate attention. Early and aggressive surgical debridement of necrotic, infected tissues and drainage of purulent collections is crucial for limb salvage. In addition, therapeutic parenteral antimicrobial therapy must be instituted immediately. When choosing an antimicrobial for the treatment of diabetic foot infections, one should consider, not only the spectrum of causative organisms and their resistance patterns, but also the efficacy, safety, and cost of therapy. Ampicillin/sulbactam has excellent broad-spectrum coverage and is the antibiotic of choice for treatment of diabetic foot infections in patients who do not have a penicillin allergy.
Edgar Borrero, M.D., FACA, FICA, Good Samaritan Hospital 786 Montauk Highway West Islip, NY 11795
FICS
References 1. Pratt TC: Gangrene and infection in the diabetic. Med Clin North Am 49:987-1004, 1965. 2. Sharp CS, Bessman AN, Wagner FW Jr, et al: Microbiology of deep tissue in diabetic gangrene. Diabetes Care 1:289-292, 1978. 3. Louie TJ, Bartlett JG, Tally FP, et al: Aerobic and anaerobic bacteria in diabetic foot ulcers. Ann Int Med 85:461-463, 1976. 4. Fierer J, Daniel D, Davis C: The fetid foot; lower extremity infections in patients with diabetes mellitus. Rev Infect Dis 1:210-217, 1979. 5. Sharp CS, Bessman AN, Wagner FW Jr, et al: Microbiology of superficial and deep tissues in infected diabetic gangrene. Surg Gynecol Obstet 149:217-219, 1979. 6. Sapico FL, Witte JL, Canawati HN, et al: The infected foot of the diabetic patient: Quantitative microbiology and analysis of clinical features. Rev Infect Dis 6:S171-S176, 1984. 7. Towne JB: Management of foot lesions in the diabetic patient. In: Vascular Surgery. Philadephia; WB Saunders Co, 1984, pp 661-669 8. Edwards PR, Ewing WH: Identification of Enterobacteriaceae, ed. 3. Minneapolis: Burgess Publising Co,
1972 9. Pickett MJ, Pedersen MM: Nonfermentative bacilli associated in man. II. Detection and identification. Am J Clin Pathol 54:164-177, 1970. 10. Holdeman LV, Cato EP, Moore WEC: Anaerobe Laboratory Manual, ed. 4. Blacksburg, Va: Anaerobe Laboratory, Virginia Polytechnic Institute and State University, 1977. 11. Gibbons GW: The diabetic foot: Amputations and drainage of infection. J Vasc Surg 5:791-793, 1987. 12. Kahn O, Wagner W, Bessman A: Mortality of diabetic patients treated surgically for lower limb infection and/ or gangrene. Diabetes 23:287-292, 1974. 13. Gibbons GW, Eliopoulos GM: Infection of the diabetic foot. In: Management of Diabetic Foot Problems. Philadelphia : WB Saunders Co. 1984, pp 97-102. 14. Finegold SM: Anaerobic bacteria: Their role in infection and their management. Postgrad Med 81:141-147, 1987. 15. Mills J: Enterococcal superinfections. Infections in Surg, 1986 Special Supplement, pp 13-16. 16. Gullberg RM, Homann SR, Phair JP: Enterococcal bacteremia: Analysis of 75 episodes. Rev Infect Dis 11:74-85, 1989.
Downloaded from ang.sagepub.com at UCSF LIBRARY & CKM on March 21, 2015
