Oral Amoxicillin Clavulanic Acid as Systemic Therapy in a Patient

Suspected with Actinomycetoma

Laila Tsaqilah, Lies Marlysa,

Risa Miliawati.

Department of Dermatology and Venereology, Faculty of Medicine, Universitas Padjadjaran - Dr. Hasan Sadikin Hospital,

Bandung 40161 Indonesia

Keywords: actinomycetoma, amoxicillin clavulanic acid, Propionibacterium propionicum.

Abstract: Actinomycetoma is a local chronic granulomatous infectious disease that affects both cutaneous and

subcutaneous tissues, and is caused by anaerobic facultative Gram-positive filamentous bacteria of the

Actinomycetaceae and Propionibacteriaceae family. Propionibacterium propionicum (family

Propionibacteriaceae) and Actinomyces species are very sensitive to beta lactam antibiotics, especially

penicillin G or amoxicillin. A rare case of actinomycetoma in a 38-year-old woman was reported. The

working diagnosis was based on clinical features and anaerobic bacterial culture from the erythematous

papules and nodules of the left arm, left elbow, right hip, and buttocks, as well as shallow ulcers on the left

buttocks, and the growth of Propionibacterium propionicum. Based on antibiotic susceptibility test results,

the patient was treated with amoxicillin clavulanic acid for 7 days. The size of ulcerative lesion with

granulation tissues became smaller. Various antibiotics combination therapy may be given to

actinomycetoma, but the combination of amoxicillin and clavulanic acid has significant effect.

1 INTRODUCTION

Mycetoma known as Maduramycosis or Madura foot

is a chronic localized granulomatous infection that

affects cutaneous and subcutaneous tissues.

Infections caused by fungi are called eumycetoma,

and actinomycetoma are caused by filamentous

bacteria (Branscomb, 2003; Sobera & Elewski, 2008;

Hay & Asbee, 2010; Hay, 2012). The filamentous

bacteria that cause mycetoma are Actinomyces sp.,

Streptomyces sp., and Nocardia sp. (Welsh et al.,

2007; Bravo et al., 2012).

Actinomycetoma is a

bacterial infection of the skin, subcutaneous tissues,

muscles, and bones with a chronic and suppurative

joint gaps, due to endemic facultative anaerobic

bacteria (Sardana et al., 2001; Bravo et al., 2012). The

Gram-positive bacilli family were Actinomycetaceae

and Propionibacteriaceae (Bravo et al., 2012).

Actinomycetoma can be diagnosed when there is one

of three clinical features, which are the existence of

an inflammatory infiltration of the skin or

subcutaneous tissue, a sinus formation with drainage,

and responsiveness to short-term antibiotics

(Reichenbach, 2009; Bravo et al., 2012).

The most

common predilections of actinomycetoma are the

legs, lower limbs, hands, head and back (Hay, 2012).

In the case reported, the lesions on the buttocks

atypical mycetoma (Chaves et al., 2002).

Actinomyces

sp. a bacteria which sensitive to beta lactam

antibiotics especially penicillin G or amoxicillin.

Therefore, the appropriate treatment options were

penicillin G or amoxicillin (Valour et al., 2014).

There were two cases of actinomycetoma treated with

amoxicillin clavulanic acid. The first case was treated

for 5 months and the second case for 6 months. There

were a clinical improvements and bone

improvements as shown by the radiological

examination. Also the absence of grain was shown by

direct mycological microscopy examination (Gomez

et al., 1993).

To our knowledge, this is a rare case of

actinomycetoma which could be treated by oral

amoxicillin clavulanic acid.

2 CASE

A 38-year-old woman, came with the chief complaint

of multiple painful ulcers on the left buttock, and

nodules on the left arm, left elbow, right waist, and

buttock that sometimes feelts itchy. Since two months

before the consultation, there were nodules on the left

arm, left elbow, right hip, and buttock that sometimes

Tsaqilah, L., Marlysa, L. and Miliawati, R.

Oral Amoxicillin Clavulanic Acid as Systemic Therapy in a Patient Suspected with Actinomycetoma.

DOI: 10.5220/0008159504510455

In Proceedings of the 23rd Regional Conference of Dermatology (RCD 2018), pages 451-455

ISBN: 978-989-758-494-7

451

felts itchy. Since a month before consultation, the

nodules on the left buttock were getting bigger and

became ulcers which were accompanied by edema

and induration around the nodules. There were no

lymphadenitis. A history of black, red, or pale grain

in the fluid from an ulcer on the left buttock was

denied.

Three weeks before the consultation, the nodules

were getting bigger. The patient went to the

dermatologist and was given systemic and topical

therapy but there was no improvement, after which

the patient was referred to the RSHS Bandung. There

was no a history of insects bite, trauma, or skin

disorders, before the ulcers appeared. The patient did

not have diabetes mellitus, tuberculosis, hepatitis, in

her family history. She was a textile worker who did

not do any gardening, farming, or working in swamps

or fish ponds. She did not have pets at home. The

hygiene of the patient was quite good. The general

status shown by the physical examination was within

normal limits. Direct microscopic examination with

10% potassium hydroxide (KOH) solution showed

that there were no hyphae nor spores. There were no

Gram positive, Gram negative, or acid-fast from the

ulcer on the left buttock. Propionibacterium

propionicum was identified by anaerobic bacterial

culture from the tissue, and the antibiotic

susceptibility test showed those to be sensitive to

amikacin, amoxcillin clavulanic acid, clindamycin,

ceftriaxone, ceftazidime, ciprofloxacin, orbenin,

gentamicin, aztreonam, and vancomycin. There was

hyalinization of fibrocollageneous tissue with

inflammation cells (lymphocytes, histiocytes,

eosinofil, and polymorphonuclear cells). The

histopathology examination showed lymphocytes on

the perivascular tissue, no spores, no hyphae, no

epitelioid datia Langhans cells or caseous necrosis.

3 DISCUSSION

Figure 1: Clinical manifestation.

RCD 2018 - The 23rd Regional Conference of Dermatology 2018

452

Figure 2: Histopathological results revealed lymphocytes on the perivascular tissue, no spores, no hyphae, no epitelioid datia

Langhans cells or caseous necrosis (hematoxylin and eosin, x400).

Mycetoma is a common disease in tropical and

subtropical developing countries (Linchon &

Khachemoune, 2006; Hay, 2012). Actinomycetoma

is more common in Central and South America. The

incidence rate of mycetoma in Indonesia has not been

clearly documented (Prasetyo & Suyoso; 2011).

Males are generally more affected than females, The

male to females rate in mycetoma patients is 3: 12

(Branscomb, 2003). Mycetoma affected mostly

adults (20 to 50 years) (Hay, 2012).

Mycetoma is

more common among people with livelihoods as

farmers, laborers, or shepherds (Bravo et al., 2012;

WHO, 2015). In this case, the patient was a 38 years

old woman that worked as a textile worker. The

commonest predilection of mycetoma are the feet

(68.7%), as in many cases their feet not protected by

footwear. In addition, mycetoma can occur on the

lower limbs (11.3%), the body (6.1%), the hands

(4%), arm (2.9%), head (2.1%), and buttocks (1,3 %).

There is one case report of mycetoma on the buttocks

which is a atypical mycetoma case in Senegal. The

lesions from that case were similar to this case report

were the affected area was the left buttock which is

an anusual predilection area.

The most common causes of actinomycetoma are

Nocardia brasiliensis, Actinomadura madurae,

Actinomadura pelletieri, and Streptomyces

somaliensis

5.12

which can be found in plants and

soils.

Whereas Actinomyces sp. and Nocardia sp. are

filamentous bacteria which have the same Class as

Actinobacteria and same Order as Actinomycetales

which can cause disease in the human skin. Aerobic

bacteria like Actinomyces sp. normally live at the

respiratory, digestive, and genitourinary systems and

can cause local suppurative disease by forming

fistulae. The aerobic environment of Nocardia sp. and

Actinomyces sp. can cause actinomycetoma (Bravo et

al., 2012). Propionibacterium propionicum known as

Actinomyces meyeri is a form of Actinomyces species

bacteria (Bravo et al., 2012). Actinomycetoma in this

case report was caused by Propionibacterium

propionicum that could be found by anaerobic

bacteria tissue culture.

The trias of mycetoma symptoms are tumefaction,

grains in the abscess, and the sinuses thorough which

that grains can emerge and reach the skin surface

(Sobera et al., 2008). At the early stages of mycetoma

the symptoms were, a small chronic solitary lesion of

painless subcutaneous nodules which have a hard or

soft consistency,

and no erythema lesion around the

nodules (Hay, 2012). The clinical forms of

actinomycetoma and eumycetoma are very similar,

but there are some differences between them. At the

early stage, the lesions of actinomycetoma are firm

nodules which tend to coalesce with the surrounding

tissues and progress rapidly (Branscomb, 2003).

Grains are the product of organisms that grow and

survive after inoculation. Grains are the components

of filamentous bacteria or fungi (Sobera & Elewski,

2008). Grain can be found in the abscess and contain

polymorphonuclear (PMN) cells, which will come

out onto the skin surface through the sinus tract (Hay,

2012). The size of the grains vary from 0.2 to 5 mm

and can be seen as sand grains attached to the sinuses

(Hay, 2012). Direct microscopic examination is

important to examine the grain because it can

determine the cause of mycetoma. Fungal grain is

black or brown, Actinomycetaceae grain is red or

pink, when the grain is white, this could be cause by

fungi and bacteria (Sobera & Elewski, 2008; Hay &

Ashbee, 2010; Hay, 2012).

A single case of

mycetoma was reported in a man who had no history

of grain. Histopathologic examination with

hematoxycillin-eosin-safran (HES) and Periodic

Acid-Schiff (PAS) staining diagnosed the patient

with mycetoma. Mycetoma can be diagnosed from

the culture of fungal and bacteria from the grains,

exudate or from tissue or aspiration (Branscomb,

2003). However, the culture often does not produce

satisfactory results due to various conditions such as,

bacterial contamination, or cultured tissue obtained

from late stage lesion containing fibrosis tissue rather

than purulent exudates. The negative cultured results

occur because the fungi did not grow as it has

received antibiotic therapy before. Direct

microscopic examination using Ziehl-Neelsen

Oral Amoxicillin Clavulanic Acid as Systemic Therapy in a Patient Suspected with Actinomycetoma

453

staining was done to detect the presence of acid fast

bacilii that could cause cutaneous tuberculosis or

infections of atypical Mycobacteria.

Polymerase chain reaction (PCR) examination

can detect the tuberculosis and nontuberculosbacteria

DNA from skin tissue. In this case report, the patient

first complained of painless nodules in the left arm,

left elbow, right hip, and buttocks since two months

before consultation. The nodules were getting bigger

and multiplied in the month before consultation and

the nodules on the left buttock became ulcers. There

was edema and indurations around the nodules. There

was no hystory of lymphadenitis or grain in the fluid

from the ulcer, no fungal growth in the fungal

cultures, no acid fast bacteria from the Ziehl-Neelsen

staining, and the results from the PCR was negative.

The results from the bacterial culture was anaerobic

bacteria (Propionibcaterium propionicum).

Histopathology examination showed hyalinisation of

the fibrocollageneous tissue with inflammation cells

(lymphocytes, histiocytes, eosinofil, and

polymorphonuclear cells), there were lymphocytes on

the perivascular tissue, no spores, no hyphae, and no

epitelioid datia Langhans cells or caseous necrosis.

The treatment of actinomycetoma could be done

with antimicrobial agents and surgery. Amputation as

a single therapy rarely gives good results. Surgery can

remove small lesions or reduce the size of the lesion.

The recommendations of drug regimens are based on

expert experience. There are no randomized

controlled trials for effective therapy regimens for

mycetoma. The treatment is given in combination

regimens to prevent drug resistance. The duration of

therapy is 3-24 months depending on the response of

the patient. The healing of the lesions can be assessed

based on subcutaneous nodules and sinus, or

indurations of the skin. Various antibiotic therapies

for actinomycetoma are aminoglycosides (amikacin

or netilmicin), rifampicin, amoxicillin-clavulanic

acid, fusidic acid, clindamycin, imipenem-silastin,

(Hay, 2012) moxifloxacin, or the tetracycline group

(oxytetracycline, minoxycline, or doxycycline)

(Bravo et al., 2012).

There is a case reporting actinomycetoma in a 32-

year-old woman treated with benzylpenicillin

8,000,000 IU injections four times daily and

cotrimoxazole tablet twice daily for twenty days,

followed by twice daily cotrimoxazole and 500 mg

amoxicillin four times daily. Two months after the

therapy there was significant improvement of sinus

fibrosis, no induration, no secretions, no new lesions,

and no systemic symptoms. The mechanism of action

of beta lactam antibiotics is bactericidal by binding to

specific proteins of penicillin-binding, inhibit

peptidoglycan synthesis and inhibit the autolithic

enzymes of bacterial cell walls. Clavulanic acid

obtained from isolated metabolite Streptomyces

clavuligerus,

can inhibit beta lactamase.

Amoxicillin-clavulanic acid has a major influence for

Gram positive and Gram negative bacteria.

In this

case the patients was given amoxicillin clavulanic

acid based on the results of antibiotic susceptibility

test against Propionibacterium propionicum and the

recommended therapy for actinomycetoma.

4 CONCLUSION

Our case demonstrates actinomycetoma with oral

amoxicillin clavulanic acid for therapy. Actinomyces

sp. can cause actinomycetoma. Propionibacterium

propionicum or known as Actinomyces meyeri is a

form of bacteria incorporated in the species

Actinomyces microorganisms cause actinomycetoma

(Bravo et al., 2012). Various regimens of antibiotics

can be given for actinomycetoma, such as

aminoglycoside group, rifampicin, amoxicillin-

clavulanic acid, fusidic acid, clindamycin, imipenem-

silastin, moxifloxacin, or tetracycline group

(oxytetracycline, minoxycline, or doxycycline).

Amoxicillin is often combined with clavulanic acid

which has a major effect on disease therapy infections

caused by Gram positive and Gram negative bacteria.

In this case patients are given amoxicillin clavulanic

acid therapy in accordance with the results of

antibiotic susceptibility test against

Propionibacterium propionicum and recommended

therapy for actinomycetoma.

REFERENCES

Branscomb, R., 2003. Mycetoma: an overview. Laboratory

Medicine. 11, pp. 803-808.

Bravo, F.G., Arenas, R., Sigall, D.A. 2012. Actinomycosis,

nocardiosis, and actinomycetoma. In: Goldsmith LA,

Katz SI, Gilchrest BA, Paller AS, Leffel DA, Wolff K,

editor. Fitzpatrick’s dermatology in general medicine.

edition. New York: McGraw-Hill. Page:2241-52.

Chávez, G., Estrada, R., Bonifaz, A., 2002. Perianal

actinomycetoma experience of 20 cases, in:

International Journal of Dermatology. pp. 491–493.

doi:10.1046/j.1365-4362.2002.01550.x

Executive Board. Mycetoma., 2015. World Health

Organization (WHO).

Gomez, A., Saul, A., Bonifaz, A., Lopez, M. 1993.

Amoxicillin and Clavulanic Acid in The Treatment Of

Actinomycetoma. International Journal of

RCD 2018 - The 23rd Regional Conference of Dermatology 2018

454

Dermatology 32, 218–220. doi:10.1111/j.1365-

4362.1993.tb02800.x

Hay, R.J., 2012. Deep fungal infection. In: Goldsmith, L.A.,

Katz, S.I., Gilchrest, B.A., Paller, A.S., Leffel, D.A.,

Wolff, K., editor. Fitzpatrick’s dermatology in general

medicine. 8

edition. New York: McGraw-Hill.

Page:2312-28.

Hay, R.J., Ashbee, H.R., 2010. Mycology. In: Burns, T.,

Breathnatch, S., Cox, N., Griffiths, C., penyunting.

Rook’s textbook of dermatology. 8

edition. Oxford:

Blackwell. Page:36.5-93.

Lichon, V., Khachemoune, A., 2006. Mycetoma: a review.

American Journal of Clinical Dermatology.

doi:10.2165/00128071-200607050-00005

Prasetyo, A.D., Suyoso, S. 2011. Retrospective study:

subcutaneous mycoses treated in the ward of

Dermatology and Venereology Department of Dr.

Soetomo General Hospital, year 2000–2009 (10 years

period). Berkala Ilmu Kesehatan Kulit dan Kelamin.

2011;23(1):17-24.

Reichenbach, J., Lopatin, U., Mahlaoui, N., Beovic, B.,

Siler, U., Zbinden, R., Seger, R.A., Galmiche, L.,

Brousse, N., Kayal, S., Güngör, T., Blanche, S.,

Holland, S.M., 2009. Actinomyces in Chronic

Granulomatous Disease: An Emerging and

Unanticipated Pathogen. Clinical Infectious Diseases

49, 1703–1710. doi:10.1086/647945

Sardana, K., Mendiratta, V., Sharma, R.C., 2001. A

suspected case of primary cutaneous actinomycosis on

the buttock. Journal of Dermatology 28, 276–278.

doi:10.1111/j.1346-8138.2001.tb00132.x

Sobera, J.O., Elewski, B.E. 2008. Fungal disease. In:

Bolognia, J.L., Jorizzo, J.L., Rapini, R.P., editor.

Dermatology. 2

edition. Edinburgh: Mosby Elsevier.

Page: 1135-57.

Valour, F., Sénéchal, A., Dupieux, C., Karsenty, J., Lustig,

S., Breton, P., Gleizal, A., Boussel, L., Laurent, F.,

Braun, E., Chidiac, C., Ader, F., Ferry, T., 2014.

Actinomycosis: Etiology, clinical features, diagnosis,

treatment, and management. Infection and Drug

Resistance. doi:10.2147/IDR.S39601

Welsh, O., Vera-Cabrera, L., Salinas-Carmona, M.C.,

2007. Mycetoma. Clinics in Dermatology 25, 195–202.

doi:10.1016/j.clindermatol.2006.05.011

Oral Amoxicillin Clavulanic Acid as Systemic Therapy in a Patient Suspected with Actinomycetoma

455