Point/Counter

Should prophylactic antibiotic therapy be used to prevent recurrent infection in patients with lymphedema?

Click here to read the Cover Story, “Awareness, early intervention needed to reduce impact of breast cancer-related lymphedema.”

POINT

Yes.

In one study, 28% of people with cancer-related lymphedema experienced cellulitis, a common complication of all types of lymphedema. In some patients, cellulitis can result in sepsis and the need for high-dependency hospital care.

Vaughan Keeley, MD
Vaughan Keeley

People with lymphedema may experience recurrent episodes of cellulitis. These can cause further damage to the lymphatic system resulting in worsening lymphedema. This, in turn, leads to an increased risk for further cellulitis. So, a vicious circle may develop.

In lymphedema, most episodes of cellulitis are felt to be Streptococcal in origin. Antibiotic prophylaxis can be helpful to reduce the risk for recurrent cellulitis of the leg. A randomized controlled trial showed that a prophylactic dose of phenoxymethylpenicillin prevented further episodes of cellulitis, but the protective effect diminished progressively following discontinuation of the antibiotic. Those with a high BMI or with lymphedema seemed to respond less well.

Clinical experience suggests that these results can be extrapolated to lymphedema of the arm following breast cancer treatment. Therefore, antibiotic prophylaxis is recommended for women with breast cancer treatment-related lymphedema who suffer recurrent episodes of cellulitis. The British Lymphology Society/Lymphoedema Support Network guidance recommends considering this if a patient suffers two or more episodes of cellulitis in 1 year. However, it also is recommended that lymphedema treatment is optimized, as there is evidence that reducing limb volume by decongestive lymphedema treatment reduces the risk for developing further cellulitis.

The antibiotic prophylaxis of choice is phenoxymethylpenicillin; this is effective against Streptococcal bacteria, is safe to use and has minimal side effects. At present, there does not seem to be any evidence of resistance to penicillin developing in Streptococcal bacteria.

The decision to use antibiotic prophylaxis is more difficult in those who are allergic to penicillin. Alternatives such as clarithromycin, doxycycline and clindamycin may be considered. However, these are not without their risks and, in some cases, predisposition to Clostridium difficile infection. Further, some Streptococci have become resistant to these alternative antibiotics. In the interest of antibiotic stewardship, therefore, careful consideration of the need for antibiotic prophylaxis is required. An alternative approach may be to reduce the risk for further cellulitis by good skin care, addressing any underlying skin conditions and optimizing lymphedema treatment. Patients may be given a supply of oral antibiotics to keep at home so they can commence a course of treatment as soon as they develop cellulitis symptoms, thereby reducing the severity of the episode and minimizing further damage to the lymphatics.

Recurrent cellulitis in women with breast cancer treatment-related lymphedema is not uncommon and can cause significant morbidity. In some patients, antibiotic prophylaxis can be used for a limited period — such as 1 to 2 years — during which time the skin condition and lymphedema can be improved. However, indefinite use may need to be considered in others who develop further recurrence of cellulitis after discontinuing antibiotic prophylaxis.

References:

Al-Niaimi F and Cox N. J Lymphoedema. 2009;4:38-42.

Brayton KM, et al. PLoS One. 2014;doi:10.1371/journal.pone.0114597.

Thomas KS, et al. N Engl J Med. 2013;doi:10.156/NEJMoa1206300.

Vaughan Keeley, MD, is consultant physician in lymphedema at Derby Teaching Hospitals NHS Foundation Trust and honorary professor at University of Nottingham. He can be reached at vaughan.keeley@nhs.net. Disclosure: Keeley reports no relevant financial disclosures.

COUNTER

No.

Rates of upper extremity lymphedema after breast cancer treatment range from 6% to 70%. A large NLN survey showed that up to 25% of patients with lymphedema report infections. Literature suggests that 10% to 20% of patients may experience recurrent infections. Although striking, these numbers are significantly lower than the rates of infections, severe symptoms and hospitalizations for infections in patients who have lower extremity lymphedema. The randomized controlled Prophylactic Antibiotics for the Treatment of Cellulitis at Home I trial demonstrated effectiveness of penicillin for preventing recurrent cellulitis of the leg. Reports suggest that some patients with recurrent cellulitis following breast cancer treatment may benefit from prophylactic antibiotics.

Laura Stewart Dominici, MD, FACS
Laura Stewart Dominici

The number of patients needed to treat to show benefit is much higher for patients with upper extremity than lower extremity lymphedema. However, it is not clear what the benefit of prophylactic antibiotics is even in that group. The most effective duration of treatment and dosing has not been established; patients continued to have recurrent infections once they stopped antibiotics. Given that antibiotics may have significant side effects that affect patient quality of life — such as anaphylactic reactions, nausea, diarrhea or rash — there is not enough evidence to suggest sufficient benefit. Concern also exists about increasing resistance to antibiotics, given rising rates of methicillin-resistant Staphylococcus aureus.

Mainstays of treatment for lymphedema include complete decongestive therapy and meticulous skin care, both of which are associated with lowering risk for recurrent cellulitis. The studies on prophylactic antibiotics did not examine impact of these treatments. For those patients with significant lymphedema not well controlled with these conservative methods, surgical procedures such as lymphatic microsurgical preventative healing approach, vascularized lymph node transfer or lymphaticovenular anastomosis can be considered.

At present, attention should be on complete decongestive therapy, good skin care, and consideration of surgical intervention for appropriate patients, and acute infections should be rapidly treated with appropriate antibiotics.

References:

Arsenault K, et al. Rehabil Oncol. 2011;29:14-20.

Dalal A, et al. Cochrane Database Syst Rev. 2017;doi:10.1002/14651858.CD009758.pub2.

Forcade NA, et al. J Am Board Fam Med. 2011;doi:10.3122/jabfm.2011.05.110073.

Inghammar M, et al. BMC Infect Dis. 2014;doi:10.1186/1471-2334-14-270.

McLaughlin SA. Oncology (Williston Park). 2012;26:242-249.

Mihara M, et al. Br J Surg. 2014;doi:10.1002/bjs.9588.

Ridner SH, et al. Lymphology. 2012;45:113-123.

Stevens DL, et al. Clin Infect Dis. 2005;doi:10.1086/497143.

Thomas KS, et al. N Engl J Med. 2013;doi:10.1056/NEJMoa1206300.

Laura Stewart Dominici, MD, FACS, is division chief of breast surgery at Brigham and Women’s Faulkner Hospital. She can be reached at ldominici@bwh.harvard.edu. Disclosure: Dominici reports no relevant financial disclosures.

COUNTER

No.

Incidence of breast cancer-related lymphedema is decreasing due to the use of sentinel lymph node biopsy and avoiding axillary lymph node dissection. The rate of lymphedema is reported to be 5% to 9% after sentinel lymph node biopsy and up to 40% among patients undergoing lymph node dissection. Development of lymphedema has been correlated with a history of arm infection. Therefore, reducing the risk for upper extremity infection has been recommended. These skin precautions include avoiding procedures that puncture the skin (vaccination, intravenous line and phlebotomy), wearing gloves while gardening, avoiding bites from pets or insects, and using skin lotion to avoid chapped skin. However, the use of prophylactic antibiotics to prevent extremity infection has been controversial and has not been widely recommended.

Akiko Chiba

A retrospective cohort study by Vignes and Dupuy evaluated the recurrence of lymphedema-associated cellulitis among patients receiving prophylactic antibiotic therapy. This study included patients with breast cancer-associated lymphedema and demonstrated that 26% developed upper extremity infection while on prophylactic antibiotic treatment. It is unclear whether prophylactic antibiotic use is of benefit. Further, the efficacy of antibiotic prophylactic treatment is transient and the recurrence risk returns to baseline after discontinuation of antibiotic prophylaxis. There are several adverse events relating to antibiotic use including development of Clostridium difficile infection, development of multidrug-resistant organisms, allergic reaction and renal toxicity.

Due to lack of data demonstrating advantages of prophylactic antibiotics over skin care precautions, routine use of prophylactic antibiotic therapy to prevent recurrent infection in breast cancer-related lymphedema patients is not widely used or recommended.

References:

DiSipio T, et al. Lancet Oncol. 2013;doi:10.1016/S1470-2045(13)70076-7.

Duvanel T, et al. Dermatologica. 1986;doi:10.1159/000249253.

Herd-Smith A, et al. Cancer. 2001;doi:10.1002/1087-0142(20011001)92:7<1783::AID-CNCR1694>3.0.CO;2-G.

Petrek JA, et al. Cancer. 2001;doi:10.1002/1097-0142(20010915)92:6<1368::AID-CNCR1459>3.0.CO;2-9.

Vignes S and Dupuy A. J Eur Acad Dermatology Venereol. 2006;doi:10.1111/j.1468-3083.2006.01648.x.

Akiko Chiba, MD, is assistant professor of surgery at Wake Forest Baptist Health. She can be reached at achiba@wakehealth.edu. Disclosure: Chiba reports no relevant financial disclosures.

Click here to read the Cover Story, “Awareness, early intervention needed to reduce impact of breast cancer-related lymphedema.”

POINT

Yes.

In one study, 28% of people with cancer-related lymphedema experienced cellulitis, a common complication of all types of lymphedema. In some patients, cellulitis can result in sepsis and the need for high-dependency hospital care.

Vaughan Keeley, MD
Vaughan Keeley

People with lymphedema may experience recurrent episodes of cellulitis. These can cause further damage to the lymphatic system resulting in worsening lymphedema. This, in turn, leads to an increased risk for further cellulitis. So, a vicious circle may develop.

In lymphedema, most episodes of cellulitis are felt to be Streptococcal in origin. Antibiotic prophylaxis can be helpful to reduce the risk for recurrent cellulitis of the leg. A randomized controlled trial showed that a prophylactic dose of phenoxymethylpenicillin prevented further episodes of cellulitis, but the protective effect diminished progressively following discontinuation of the antibiotic. Those with a high BMI or with lymphedema seemed to respond less well.

Clinical experience suggests that these results can be extrapolated to lymphedema of the arm following breast cancer treatment. Therefore, antibiotic prophylaxis is recommended for women with breast cancer treatment-related lymphedema who suffer recurrent episodes of cellulitis. The British Lymphology Society/Lymphoedema Support Network guidance recommends considering this if a patient suffers two or more episodes of cellulitis in 1 year. However, it also is recommended that lymphedema treatment is optimized, as there is evidence that reducing limb volume by decongestive lymphedema treatment reduces the risk for developing further cellulitis.

The antibiotic prophylaxis of choice is phenoxymethylpenicillin; this is effective against Streptococcal bacteria, is safe to use and has minimal side effects. At present, there does not seem to be any evidence of resistance to penicillin developing in Streptococcal bacteria.

The decision to use antibiotic prophylaxis is more difficult in those who are allergic to penicillin. Alternatives such as clarithromycin, doxycycline and clindamycin may be considered. However, these are not without their risks and, in some cases, predisposition to Clostridium difficile infection. Further, some Streptococci have become resistant to these alternative antibiotics. In the interest of antibiotic stewardship, therefore, careful consideration of the need for antibiotic prophylaxis is required. An alternative approach may be to reduce the risk for further cellulitis by good skin care, addressing any underlying skin conditions and optimizing lymphedema treatment. Patients may be given a supply of oral antibiotics to keep at home so they can commence a course of treatment as soon as they develop cellulitis symptoms, thereby reducing the severity of the episode and minimizing further damage to the lymphatics.

Recurrent cellulitis in women with breast cancer treatment-related lymphedema is not uncommon and can cause significant morbidity. In some patients, antibiotic prophylaxis can be used for a limited period — such as 1 to 2 years — during which time the skin condition and lymphedema can be improved. However, indefinite use may need to be considered in others who develop further recurrence of cellulitis after discontinuing antibiotic prophylaxis.

References:

Al-Niaimi F and Cox N. J Lymphoedema. 2009;4:38-42.

Brayton KM, et al. PLoS One. 2014;doi:10.1371/journal.pone.0114597.

Thomas KS, et al. N Engl J Med. 2013;doi:10.156/NEJMoa1206300.

Vaughan Keeley, MD, is consultant physician in lymphedema at Derby Teaching Hospitals NHS Foundation Trust and honorary professor at University of Nottingham. He can be reached at vaughan.keeley@nhs.net. Disclosure: Keeley reports no relevant financial disclosures.

PAGE BREAK

COUNTER

No.

Rates of upper extremity lymphedema after breast cancer treatment range from 6% to 70%. A large NLN survey showed that up to 25% of patients with lymphedema report infections. Literature suggests that 10% to 20% of patients may experience recurrent infections. Although striking, these numbers are significantly lower than the rates of infections, severe symptoms and hospitalizations for infections in patients who have lower extremity lymphedema. The randomized controlled Prophylactic Antibiotics for the Treatment of Cellulitis at Home I trial demonstrated effectiveness of penicillin for preventing recurrent cellulitis of the leg. Reports suggest that some patients with recurrent cellulitis following breast cancer treatment may benefit from prophylactic antibiotics.

Laura Stewart Dominici, MD, FACS
Laura Stewart Dominici

The number of patients needed to treat to show benefit is much higher for patients with upper extremity than lower extremity lymphedema. However, it is not clear what the benefit of prophylactic antibiotics is even in that group. The most effective duration of treatment and dosing has not been established; patients continued to have recurrent infections once they stopped antibiotics. Given that antibiotics may have significant side effects that affect patient quality of life — such as anaphylactic reactions, nausea, diarrhea or rash — there is not enough evidence to suggest sufficient benefit. Concern also exists about increasing resistance to antibiotics, given rising rates of methicillin-resistant Staphylococcus aureus.

Mainstays of treatment for lymphedema include complete decongestive therapy and meticulous skin care, both of which are associated with lowering risk for recurrent cellulitis. The studies on prophylactic antibiotics did not examine impact of these treatments. For those patients with significant lymphedema not well controlled with these conservative methods, surgical procedures such as lymphatic microsurgical preventative healing approach, vascularized lymph node transfer or lymphaticovenular anastomosis can be considered.

At present, attention should be on complete decongestive therapy, good skin care, and consideration of surgical intervention for appropriate patients, and acute infections should be rapidly treated with appropriate antibiotics.

References:

Arsenault K, et al. Rehabil Oncol. 2011;29:14-20.

Dalal A, et al. Cochrane Database Syst Rev. 2017;doi:10.1002/14651858.CD009758.pub2.

Forcade NA, et al. J Am Board Fam Med. 2011;doi:10.3122/jabfm.2011.05.110073.

Inghammar M, et al. BMC Infect Dis. 2014;doi:10.1186/1471-2334-14-270.

McLaughlin SA. Oncology (Williston Park). 2012;26:242-249.

Mihara M, et al. Br J Surg. 2014;doi:10.1002/bjs.9588.

Ridner SH, et al. Lymphology. 2012;45:113-123.

Stevens DL, et al. Clin Infect Dis. 2005;doi:10.1086/497143.

Thomas KS, et al. N Engl J Med. 2013;doi:10.1056/NEJMoa1206300.

Laura Stewart Dominici, MD, FACS, is division chief of breast surgery at Brigham and Women’s Faulkner Hospital. She can be reached at ldominici@bwh.harvard.edu. Disclosure: Dominici reports no relevant financial disclosures.

PAGE BREAK

COUNTER

No.

Incidence of breast cancer-related lymphedema is decreasing due to the use of sentinel lymph node biopsy and avoiding axillary lymph node dissection. The rate of lymphedema is reported to be 5% to 9% after sentinel lymph node biopsy and up to 40% among patients undergoing lymph node dissection. Development of lymphedema has been correlated with a history of arm infection. Therefore, reducing the risk for upper extremity infection has been recommended. These skin precautions include avoiding procedures that puncture the skin (vaccination, intravenous line and phlebotomy), wearing gloves while gardening, avoiding bites from pets or insects, and using skin lotion to avoid chapped skin. However, the use of prophylactic antibiotics to prevent extremity infection has been controversial and has not been widely recommended.

Akiko Chiba

A retrospective cohort study by Vignes and Dupuy evaluated the recurrence of lymphedema-associated cellulitis among patients receiving prophylactic antibiotic therapy. This study included patients with breast cancer-associated lymphedema and demonstrated that 26% developed upper extremity infection while on prophylactic antibiotic treatment. It is unclear whether prophylactic antibiotic use is of benefit. Further, the efficacy of antibiotic prophylactic treatment is transient and the recurrence risk returns to baseline after discontinuation of antibiotic prophylaxis. There are several adverse events relating to antibiotic use including development of Clostridium difficile infection, development of multidrug-resistant organisms, allergic reaction and renal toxicity.

Due to lack of data demonstrating advantages of prophylactic antibiotics over skin care precautions, routine use of prophylactic antibiotic therapy to prevent recurrent infection in breast cancer-related lymphedema patients is not widely used or recommended.

References:

DiSipio T, et al. Lancet Oncol. 2013;doi:10.1016/S1470-2045(13)70076-7.

Duvanel T, et al. Dermatologica. 1986;doi:10.1159/000249253.

Herd-Smith A, et al. Cancer. 2001;doi:10.1002/1087-0142(20011001)92:7<1783::AID-CNCR1694>3.0.CO;2-G.

Petrek JA, et al. Cancer. 2001;doi:10.1002/1097-0142(20010915)92:6<1368::AID-CNCR1459>3.0.CO;2-9.

Vignes S and Dupuy A. J Eur Acad Dermatology Venereol. 2006;doi:10.1111/j.1468-3083.2006.01648.x.

Akiko Chiba, MD, is assistant professor of surgery at Wake Forest Baptist Health. She can be reached at achiba@wakehealth.edu. Disclosure: Chiba reports no relevant financial disclosures.