Rifampicin versus Doxycycline in Prevention of recurrent Boils

(A Comparative Therapeutic Study)

 

Rzan A. Al-Battat1, Basman Medhat Fadheel2, Shatha Al-Bayati3

1Dermatologist at College of Medicine Baghdad University, Iraq.

2College of Medicine Baghdad University, Iraq.

3Dermatologist at Al-Yarmouk teaching hospital, Baghdad, Iraq.

*Corresponding Author E-mail: rzan.a@comed.uobaghdad.edu.iq, bmflili@yahoo.com, Shatha99a@yahoo.com, gooacc29@gmail.com

 

ABSTRACT:

Background: Suffering from recurrent boils (furunclosis) is a common problem in our locality as it is noticed by many dermatologists especially in association with increasingly hot weather. The most common causative organisms are staphylococci. Objective: The aim of the study was to shed the light upon this problem and compare two systemic therapeutic agents for the prevention of recurrence, doxycycline and rifampicin. Patient and method: One hundred thirty-five (135) Patients with recurrent boils from Al-Yarmouk teaching hospital dermatology outpatient department were included in this study; age ranged from 10 to 64 years old and out of total patients 32 were males and 103 were females. Patients were assessed by full history and clinical examination done by dermatologist. An aspirate from the content of the boil was taken from 30 patients for bacteriological culture. The patients were treated by topical with or without systemic anti-staph antibiotics followed by a preventive protocol of doxycycline100mg twice daily for two months duration in 50 patients and rifampicin 600mg for ten days in the other 85 patients. Both groups used topical sodium fucidate 2% ointment twice daily in nostrils, axilla and perineum for ten days. All were followed up for 2 years to assess the recurrence after treatment. Results: Out of 135 patients treated, 3 (2.22%) patients defaulted from follow up (they were from doxycyclin group) and out of the remainder 132, only 9 (6.8%) patients had recurrence after treatment; 7 (14.89%) patients from the doxycycline group and 3(3.52%) patients from rifampicin group. Forty 40 (85.1%) patients responded well to doxycycline without recurrence for 2 years compared to 83 (97.65%) patients treated with Rifampicin with no recurrence during the 2 years of follow up. The noticed side effects were gastric upset in doxycycline and urine discoloration in rifampicin. Conclusion: Rifampicin regimen in prevention of recurrent boils significantly showed higher effectiveness in addition to more tolerable, easier, shorter course, and fewer side effects than doxycyclin.

 

KEYWORDS: Recurrent boils, Furenclosis, Staphylococcus aureus, Rifampicin, Doxycycline.

 

 


INTRODUCTION:

Recurrent furunclosis (boils) is a common problem especially in Iraq as it is noticed by many dermatologists especially in association with increasingly hot weather during summer season. Furuncle (boil) is a deep infection of the hair follicle causing tissue destruction with formation of pus and necrotic tissue.

 

Boiles appear as red, swollen, and tender nodules on hair-bearing areas of the body1,2. The commonest causative agent is Staphylococcus aureus (S.aureus) that is coagulase positive3,4, however, other bacteria may also be causative like streptococci and other microorganisms could be obtained by cultures from the skin lesions5.

 

Most of the patients with recurrent boils are actually carriers. Humans are natural reservoirs of S. aureus. About thirty to 50 percent of adults are colonized with staphylococci, with 10 to 20 percent persistently colonized. Both methicillin-sensitive and methicillin-resistant isolates are persistent colonizers. Those who are colonized with S. aureus are at higher risk for recurrent infections6,7. In another word recurrent staphylococcal skin infections raise the question of probable colonization by Staphylococcus aureus and the need for eradication to stop this recurrence8,9.

 

There are many predisposing factors for recurrent boils like diabetes mellitus, associated skin diseases such as atopic dermatitis, positive family history, and multiplicity of lesions, anemia, and history of antibiotic therapy, hospitalization, personal hygiene, and immunity problems10,11. Furunculosis (boils) increased in the United States due to CA-MRSA (community associated methicillin resistant staphylococcus aureus) epidemic and the resistant organism’s close association with the Panton–Valentine leucocidin (PVL) virulence factor. This factor is associated with follicular infections and strongly associated with furunculosis and its recurrence. Most cases of furunclosis in United States are caused by CA-MRSA, while elsewhere in the world they are mostly caused by methicillin-sensitive S. aureus (MSSA)12,13.

 

In a study in Iraq, approximately 46.1% of S. aureus were MRSA, with increase in numbers of yearly isolates with most MRSA were community-acquired with limited nosocomial spread15, Nasal carriage of S. aureus is main risk factor for recurrent boils and occurs in 60% of individuals 12. Furuncle (boil) usually presents as a painful tender papule that soon enlarge to become a nodule surrounding a hair, it may fluctuate or reveal a drop of pus upon squeezing pressure. Recurrence could be defined as three or more attacks of boils within the previous twelve months 10.

 

The patient may have increased body temperature or an enlarged possibly tender lymph node in draining area, the condition could be complicated by abscess formation especially if untreated especially in some sites like perianal areas. Other complications include cellulitis, sinus, fistula, abscess, distance abscess, osteomyelitis, local scars and or hyperpigmentation16,17,18. The underling pathogenesis of boils is staphylococcal or other bacterial infection of the deep part of the hair follicle; with suppurative Inflammation and pus formation mainly because of bacterial lytic enzymes like protease, lipase and lecithinase19. A boil or furuncle usually treated successfully by drainage if there was any bus collected, topical antibiotic like fucidic acid or mupirocin with or without systemic antistaphylococal antibiotic like amoxicillin-clvulonic acid (coamoxclav) or floxacillin, but the problem is how to prevent recurrence when this condition is frequently             recurring16,20.

 

Many antimicrobial agents have been used to prevent recurrence or to irradicate carrier state. Tetracyclines (doxycycline and minocycline) had been used for management of recurrent skin infections with both MRSA and MSSA (methicillin sensitive Staphylococcus aureus)1. Prolonged antimicrobial prophylaxis like erythromycin 250 mg twice daily for 18 months have been used to prevent recurrent skin infections like cellulitis or erysipelas due to methicillin sensitive staphylphylococci; proving that prolonged antimicrobial prophylaxis is effective in preventing recurrent episodes of soft-tissue infections, however such long courses are not free from side effects21. Azithromycin also found to be effective in treatment and prevention of recurrent furunculosis due to methicillin sensitive Staphylococcus aureus in 3 months of weekly 500 mg dose22, other antibiotics used for the same purpose include oral clindamycin, sodium fusidate or trimethoprim plus sulfamethoxazole depending on susceptibility of the organism in addition to treatment of the underlying cause of infection which is an important step in management23. Fuoroquinolones also used in some cases of MRSA carriage21, 22.

 

Rifampicin also have been used to manage difficult cases of recurrent boils13. Rifampicin (Rif) is one of the most potent broad spectrum antibacterial  and is used as a main drug in anti-tuberculosis therapy. It acts by inhibiting the bacterial RNA polymerase. Rifampicin is bactericidal, diffuses freely to the tissues and cells24,25. Some studies revealed that rifampicin is beneficial in the treatment of (MRSA) in combination with other antibiotics like a β-lactam or vancomycin and concluded that adding rifampicin improves the outcomes in staphylococcus aureus bacteremia26. Rifampicin  is better to be taken on an empty stomach, absorbed easily from intestine metabolized in the liver excreted mainly in feces and to lesser extent in urine it is generally well tolerated with urine (and sometimes other body fluids) discoloration being the most noticeable side effect; others include nausea vomiting diarrhea ,skin rash and rarely hepatotoxicity. Since it is a powerful enzyme inducer it may decrease the efficacy of many other drugs like warfarin, contraceptives and others 27.

 

Doxycycline is a broad-spectrum antibiotic of tetracycline class. It is bacteriostatic acts by inhibition of protein production28. It is Absorbed from the stomach and the upper small intestine. Absorption of doxycycline is impaired by milk products, sodium bicarbonate, aluminum hydroxide gels, calcium and magnesium salts, and iron preparations, so it is better to take doxycycline on an empty stomach. Its side effects include gastrointestinal upset, nausea, vomiting and diarrhea. Oral doxycycline can cause pill esophagitis, especially if it is swallowed without adequate amount of water18. It increases risk of sunburn and may cause skin rash. Use after the first trimester of pregnancy or in young children may cause discoloration of teeth, so it is usually not used underage of ten years. Its use during breastfeeding is probably safe28. Many topical agents have been used in staphylococcal infections in general and specifically furuncolosis for treatment and prevention of recurrence or eradication of carrier state whether the causative agent was MRSA or MSSA strains, the most important of these topicals are sodium fusidate 2% ointment (or fucidic acid 2% cream) and mupirocin (pseudomonic acid) 2% ointment1. General hygienic measures are especially important in decreasing the recurrence like regular bathing, frequent hand washing and household cleanliness2,5,7.

 

The aim of the study was to shed the light upon the problem of recurrent boils, to assess its response to antibiotic preventive treatment with rifampicin and doxycycline in comparison with each other.

 

Patients and method:

One hundred thirty-five (135) patients with recurrent boils from Al-Yarmouk teaching hospital dermatology outpatient department where included in this study in the duration between 1st of June 2016to 1st of January 2017 and followed up for at least two years (2017 and 2018) to January 2019. Patients were 32 (23.7%) males and 103 (76.3%) females with ages ranging from 10 to 64 years old. Recurrence was defined as repeated appearance of boils for three times or more during the last twelve months. Patients were assessed by history and clinical examination done by dermatologist. Exclusion criteria include patients who were sensitive to any of drugs used in the study, patients less than 10 years’ age, women who were pregnant or on contraceptives, patients with a renal or hepatic impairment and any patient who was on treatment that interacts with the drugs we use was excluded.

 

In the first visit an aspirate from the content of the boil was taken for bacteriological culture and sensitivity test from the first 30 patients. The test was done in the hospital’s laboratory. Bus was drained if present. All the patients were treated with topical sodium fusidate 2% ointment twice daily until healing of the lesion along with the use of hydrogen peroxide soap 2.5% for bathing and hand washing from the first visit for two weeks duration. Oral co-amoxiclav tablets (in a dose of 625mg or 375mg three times per day according to age, body weight and severity) was used in severe conditions with multiple boils, cellulitis, abscess or when fever is present for a duration of 5 to7 days according to the severity.

 

In the second visit after 5-7 days the response was assessed, and patients were given the treatment for prevention of recurrence. Fifty (50) patients were given doxycycline 100mg twice daily for two months duration, along with topical sodium fusidate 2% ointment twice daily in three sites: nostrils, perineum and axilla for the first ten days of this duration. The other 85 patients were given rifampicin 600 mg single morning dose (in form of two300mg capsules) for 10 days and they were informed that urine will turn red due to this treatment (to reassure them) in addition to the use of sodium fusidate 2% ointment in the same way and duration as in the doxycyclin group. Patients in both groups were given the instructions regarding general hygienic measures that include regular bathing, frequent hand washing and household cleanliness. Both groups were given the mobile number of the researcher dermatologist to inform the later about any side effects and recurrence if happened. Follow up continued two years to record any recurrence. At the end of follow up period the dermatologist contacts the patient by phone to ensure if there was any missed recurrence.

 

A prospective clinical comparative therapeutic study, descriptive, and analytical statistics were done. The data was evaluated by statistical program SPSS (Statistical Package for Social Sciences, Chicago, USA) Version 11.0. Frequency tables were used to describe the categorical variables. P value<0.05 considered significant. The agreement of ethical and scientific committee in department of medicine in college of medicine Baghdad University was taken before establishing the study. In addition to the agreement of each patient (or the parents if under eighteen) that was taken orally and individually.

 

RESULTS:

Total patients’ number was 135 patients; 32 (23.7%) males and 103 (76.3%) females with ages ranging from 10 to 64 years old. (Mean age 31.95±11.69)

 

 

Table 1: Age distribution among patients

 

N

Minimum

Maximum

Mean (± Std. Deviation)

Age

135

10

64

31.95 (±11.69)

 

Table 2: Mean age of patients grouped by gender

Gender

N

% of Total N

Mean Age (± Std. Deviation)

Male

32

23.7%

32.91 (±7.28)

Female

103

76.3%

31.65 (±12.77)

Total

135

100.0%

31.95 (±11.69)

 

Culture was done for 30 patients of them. Twenty five (83.33 %) of the patients cultures reveals staphylococcus aureus, 3 cultures (10%) reveal streptococci, 1 (3.33%) reveals klebsiella and 1 (3.33%) reveals E.coli.

 

Table 3: Types of causative bacteria according to the culture

Staphylococcus aureus

Streptococci

Klebsiella

E. coli

Total

25

3

1

1

30

83.33%

10.00%

3.33%

3.33%

100%

 

The sensitivity test reveals that all S.aureus strains were methicillin sensitive. The entire patients (100%) respond very well to the initial treatment with drainage, hydrogen peroxide 2.5% soap, topical sodium fucidate and co-amoxiclav if needed. Regarding the group treated with doxycycline; 3 (6%) patients defaulted, so 47 patients completed the follow up, only 7 (14.89%) patients developed recurrence after treatment, 40 (85.1 %) patients have no recurrence during 2 years follow up. Patients’ earliest recurrence occurred after 6 months duration after completing treatment. The most common side effect was gastric upset that occurred in 6 patients (12.7%). Regarding the 85 patients who were treated with rifampicin only 2 patients developed recurrence (2.35%); while 83 (97.65%) patients have no recurrence during 2 years follow up. Patients’ earliest recurrence occurred after 16 months duration after completing treatment. The most common side effect was urine discoloration that occurred in all patients (100%) but none of them complaint from any other side effect.

 

Statistically significant difference was found in recurrence with different treatment options (p value = 0.010) with Rifampicin having lower recurrence of 2.35% when compared to 14.89% recurrence with Doxycycline.


 

Figure1: Culture Results

 

Table 4: Recurrence by medication type (During 2 years of follow up)

Medication

Total Patients

Defaulted (%)

Followed Up

Recurrence

No recurrence

P- Value

(%)

(%)

Doxycycline

50

3

(6.00%)

47

7 (14.89%)

40 (85.11%)

0.010

Rifampicin

85

0

(0.00%)

85

2 (2.35%)

83 (97.65%)

P value < 0.05 is considered significant

 


 

Figure 2: Recurrence in two years per drug

 

Figure 3: Onset of earliest recurrence per drug in months

The correlation of age, gender and family history with recurrence of condition was explored but no statistical significance was discovered.

 

DISCUSSION:

Staphylococcal infections especially boil and recurrent boils are fairly common in our locality especially during hot season so we need to prove the causative agent, to determine the effectiveness of primary treatment, and to compare the preventive treatment. The culture was carried out for small group of our patients and it reveals that the most common causative agent was staphylococcus aureus as we did expect and as had been proved by many previous studies so there was no need to repeat the same work29,30. The sensitivity test reveals that all 25 S.aureus isolates were methicillin sensitive, and this not necessarily means that MRSA is not present it is more likely due to small number cultured. Regarding the effectiveness of primary treatment with drainage of bus, topical sodium fusidate 2% ointment and co-amoxiclav orally when needed along with 2.5% hydrogen peroxide soap (for regular bathing and hand washing for two weeks) fortunately it was effective and similar type of treatment was recommended by many other studies31.

 

The most important part of the study reveals that both doxycycline and rifampicin were effective preventive treatment for recurrence. Rifampicin 600mg daily along with topical sodium fusidate 2% ointment in possible colonization sites for ten days was effective in (97.65%) of patient in recurrence prevention during two years of follow up with shorter (only ten days) and easier (single morning dose) course so has better patient compliance and less side effect apart from the red discoloration of urine that the patient formerly informed about so causes no problem. Rifampicin has been used previously for prevention of recurrent staphylococcal infections with variable rates of success(32,33). Doxycycline as was effective in prevention for recurrence in (85.11%) of patients, but it has obviously longer course, multiple dosage and causes noticeable gastric upset in few patients. Similar finding was noticed in other studies34.

 

Another important note is that there were some protocols that advise the use of topical antibiotics like sodium fusidate acid ointment at sites of carriage of staphylococci; in the nose, axilla and perineum33. It was used it in order to decrease the recurrence that result from probable colonization at these sites, to potentiate the effect of the two systemic drugs we wanted to study and decrease probable resistance so the successes rates we achieved in prevention of recurrence with rifampicin and doxycycline; (97.65%) and (85.11%) respectively was comparable to the results of eradication achieved by studies using other algorithms of one month duration oral antibiotics which was 90% for MRSA and 83.4% for non MRSA colonization(8), taking in consideration that we have recurrence in 7 out of 132 patient(5.3%) during two years follow up while on the mentioned study 18 patient out of 79 colonized patients (22.7%) recurred during three years follow up. The other factor that helped us in achieving these high success rates could be the use of 2.5% hydrogen peroxide soap for general hygiene in the first two weeks of management. We chose it because the mechanism of action of hydrogen peroxide is due to its oxidation effect. The oxidation of the different molecules within the microorganisms will result in disruptions in structure and function and the loss of their viability or infectivity35,36. The general mechanism of action of hydrogen peroxide reduces the risk of development of resistance to the antimicrobial agents over time37,38.

 

CONCLUSION:

The most common cause for recurrent boils was staphylococcus aureus. Drainage of bus, topical sodium fusidate ointment and co-amoxiclav orally when needed along with 2.5% hydrogen peroxide soap (for regular washing for two weeks) was effective primary treatment of boils. Both doxycycline and rifampicin along with topical sodium fusidate 2% ointment in possible colonization sites were effective preventive treatment for recurrence. Rifampicin was significantly more effective in recurrence prevention; with less side effects, shorter, easier course and better tolerance. This work may helps to control a common type of skin infections in this country among all age groups from early childhood on.

 

RECOMMENDATION:

We recommend topical sodium fusidate ointment and co-amoxiclav orally when needed along with 2.5% hydrogen peroxide soap (for regular washing for two weeks) as effective primary treatment of boils and rifampicin 600mg daily for ten days along with topical sodium fusidate 2% ointment in possible colonization sites to prevent recurrence in cases of recurrent boils.

 

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Received on 24.12.2021            Modified on 24.02.2022

Accepted on 26.03.2022           © RJPT All right reserved

Research J. Pharm. and Tech 2022; 15(7):3041-3046.

DOI: 10.52711/0974-360X.2022.00508