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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 10  |  Issue : 4  |  Page : 358-363

The burden of mycobacteria species among children from postvaccination abscess in Southern India


1 Department of Microbiology, Aarupadai Veedu Medical College and Hospital, Puducherry, India
2 Child Surgical Clinic, Cuddalore, Tamil Nadu, India
3 Department of Anesthesiology, Sri Lakshmi Narayana Medical College and Hospital, Puducherry, India
4 Department of Paediatrics, AVM Multi Speciality Hospital, Thoothukudi, Tamil Nadu, India
5 Department of Paediatrics, Tianjin Medical University, Tianjin, China
6 Department of Surgery, Aarupadai Veedu Medical College and Hospital, Puducherry, India

Date of Submission16-Sep-2021
Date of Decision10-Oct-2021
Date of Acceptance06-Nov-2021
Date of Web Publication13-Dec-2021

Correspondence Address:
Latha Ragunathan
Department of Microbiology, Aarupadai Veedu Medical College and Hospital, Puducherry
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijmy.ijmy_190_21

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  Abstract 


Background: From the time vaccines were introduced, their impact has been beyond measurable. Mycobacteria are pathogens increasingly isolated from postvaccination abscess. Identification of these pathogens plays a very crucial role in the management of these babies. We aimed to determine Mycobacterial spp occurrence from vaccination abscess, draw local antibiogram, and guide management of babies with vaccination abscess. Methods: Babies with postvaccination abscess from 2016 to 2020 were included. Pus collected during incision and drainage was processed as per the standard guidelines. Mycobacterium isolates were identified by conventional methods, and all samples were confirmed by polymerase chain reaction. All babies underwent incision and drainage, and all were started with amoxicillin and clavulanic acid and changed later as per the sensitivity report. Results: Mycobacterium abscessus was isolated from 17% (12) pus samples from 71 postdiphtheria pertussis and tetanus vaccination, and Mycobacterium bovis was isolated from 83.3% (10) babies with post-Bacillus Calmette–Guérin vaccination. The mean interval between injection and abscess formation was 32.75 days in case of M. abscessus, whereas it was 50.4 days in case of M. bovis. All the M. abscessus were sensitive to linezolid, amikacin, and clarithromycin, whereas no treatment except incision and drainage was required for M. bovis. Conclusion: There is an increased incidence of Mycobacterial spp infection in postvaccination abscess. All babies with M abscessus responded well with combination antibiotic therapy plus drainage of abscesses, whereas M. bovis was treated by incision and drainage, and no further antibiotics were given.

Keywords: Bacillus Calmette–Guérin, diphtheria pertussis and tetanus, Mycobacterium abscessus, Mycobacterium bovis


How to cite this article:
Kavitha K, Ragunathan L, Elantheriyan P, Gopalakrishnan K, Gopala KA, Balamurugan ID, Navya RR, Marcella SS, Venkatachalam GK. The burden of mycobacteria species among children from postvaccination abscess in Southern India. Int J Mycobacteriol 2021;10:358-63

How to cite this URL:
Kavitha K, Ragunathan L, Elantheriyan P, Gopalakrishnan K, Gopala KA, Balamurugan ID, Navya RR, Marcella SS, Venkatachalam GK. The burden of mycobacteria species among children from postvaccination abscess in Southern India. Int J Mycobacteriol [serial online] 2021 [cited 2022 Jan 25];10:358-63. Available from: https://www.ijmyco.org/text.asp?2021/10/4/358/332355




  Introduction Top


The advent of vaccination has undoubtedly revolutionized the field of infectious disease prevention in most health-care systems.[1] Nevertheless, the administration of vaccines has its fair share of possible side effects such as the formation of pyogenic abscesses.[2] Postvaccination abscesses due to rapidly growing mycobacteria (RGM) were the first disease to be recognized in epidemic form.[3] Vandepitte et al. in their study described an outbreak which began in 1960 in a hospital in Kinshasa, Congo, of 100 cases of postinjection abscesses.[4],[5] Since then, seven more outbreaks of postinjection abscesses due to RGM have been reported.[3]

Mycobacterial infection results in extended wound healing times with formation of chronic serous discharge. Consequently, this prolongs the use of broad-spectrum antibiotics[6],[7] and thus increases the risk of producing antibiotic resistance as well as putting the child at risk of potential side effects. Therefore, higher diagnostic suspicion toward Mycobacterial spp is required to reduce the child's morbidity. Furthermore, prompt identification of the pathogens results in swift administration of the correct treatment regimens. As a result, a study was conducted in a tertiary care hospital, Puducherry, to analyze the magnitude of mycobacterial infections from postvaccination abscess and their clinical presentation and to draw a local antibiogram for the same to guide the pediatricians and surgeons for prompt diagnosis and treatment.


  Methods Top


The current study included babies diagnosed with postvaccination injection site abscess attending the pediatrics and surgery department in a tertiary care hospital from October 2016 to November 2020. This prospective study was initiated after approval from ethics committee. Appropriate demographic details were collected. The type of clinical presentations such as swelling, erythema, induration, fever, and discharge was recorded.

Microbiological investigation

Pus drained during incision and drainage was sent to microbiology department. Gram stain was done, and the pus was processed in blood agar, MacConkey agar, and thioglycolate broth. Plates were incubated at 37°C. The isolated organisms were identified as per the standard bacteriological techniques.[8] Antibiotic sensitivity testing was done by Kirby–Bauer method following Clinical and Laboratory Standards Institute (CLSI) guidelines.[9] The sterile samples were further screened for acid-fast bacilli by Ziehl–Neelsen and inoculated in Lowenstein–Jensen (LJ) media for culturing the same. The growths on LJ media were further processed for additional tests, as shown in [Table 1], to confirm the identity of the organism. Antibiotic sensitivity testing was done by standard method[10] for amikacin, clarithromycin, and linezolid. All isolates were subjected to polymerase chain reaction (PCR) for confirmation.
Table 1: Biochemical test for identification of Mycobacterial spp.

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All babies underwent incision and drainage, and all were started with amoxicillin and clavulanic acid as per their body weight. Later, antibiotics were changed as per the sensitivity report. All babies [Figure 1], [Figure 2], [Figure 3], [Figure 4] with Mycobacterium abscessus were treated with antibiotics for 3 weeks. All babies responded well with no recurrence [Figure 5] and [Figure 6]. Babies [Figure 7], [Figure 8], [Figure 9] with post-Bacillus Calmette–Guérin (BCG) vaccination abscess by Mycobacterium bovis required only incision and drainage, and no further treatment was required.
Figure 1: Large abscess with skin stretch

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Figure 2: Diffuse post vaccination abscess

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Figure 3: Evolving post vaccination abscess

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Figure 4: Post vaccination abscess with erythema

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Figure 5: Healed abscess after treatment

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Figure 6: Resolved thigh abscess after treatment

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Figure 7: Post BCG vaccination abscess

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Figure 8: Abscess with skin involvement

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Figure 9: Localised post BCG abscess

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  Results Top


Eighty-five babies diagnosed with postvaccination abscess were included in our study. Majority of the babies were female (47 were female and 38 were male babies). All babies had undergone vaccination under various clinical settings. Among them, 71 babies had undergone diphtheria pertussis and tetanus (DPT) vaccine vaccination, and 12 babies had BCG vaccination. No major disease comorbidities or causes of immunosuppression were identified among the babies.

Types of microorganisms isolated from post-DPT injection site abscess and BCG are shown in [Table 2]. Of the 71 pus samples examined from post-DPT vaccination abscess, 33 (46.5%) were sterile abscess. Gram stain and Ziehl–Neelsen (ZN) stains showed no organisms and no acid-fast bacilli, respectively. The babies underwent incision and drainage alone, and no further antibiotics were given. Staphylococcus aureus was the most common pathogen isolated in 33.8% (24) samples [Table 2]. The babies were initially treated with amoxicillin–clavulanate and later changed as per the antibiotic sensitivity report. The lesions healed well in 5 days.
Table 2: Types of microorganisms isolated from postdiphtheria pertussis and tetanus injection site abscess and Bacillus Calmette–Guérin

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M. abscessus was isolated in 17% (12) samples. The demographic details are shown in [Table 3]. Initially, culture was sterile after 48 h and Gram stain showed no organisms; however, when ZN staining was performed, all the samples were acid-fast bacilli positive, and the culture yielded growth ranging between 4 and 7 days. Initially the isolates were identified as RGM and were further characterized in our laboratory as M. abscessus by standard criteria that included growth rate, morphologic structure, and biochemical tests results. All samples were tested by multiplex PCR which also confirmed as M abscessus.
Table 3: Summary of  Mycobacterium abscessus Scientific Name Search i>Mycobacterium bovis isolated from our hospital

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Cutaneous findings included subcutaneous abscesses and nonhealing ulcers. Systemic symptoms such as fever or a chill were absent in all babies. All babies were initially treated with incision and drainage and started with amoxicillin/clavulanate.

All isolates analyzed for antimicrobial susceptibility patterns were sensitive to clarithromycin, linezolid, and amikacin. All babies with M. abscessus were treated with clarithromycin and amikacin. The babies responded well and started healing in 7 to 10 days and absolutely cured in 14 days.

Of the 14 post-BCG vaccination abscesses, ten (83.3%) yielded M. bovis and one S. aureus (8%). M. bovis strain was identified as it was negative in a pyrazinamidase test, an assay used for presumptive differentiation between Mycobacterium tuberculosis and M. bovis. The result of this test was compatible with M. bovis/BCG. All samples were further confirmed by PCR.


  Discussion Top


The impact of vaccinations has been immense. Since the start of the vaccination era, vaccines have protected children from numerous debilitating infectious diseases.[11] BCG remains the only widely used vaccine against tuberculosis (TB).[12] Hence, BCG vaccination is accepted as an important preventive measure in many national TB programs.[13] The advantages of vaccinations far outweigh the risks.[2] It has been suggested that almost all the issues stemming from the procedure are associated with local trauma of the injection or by the local irritation of the drug. Many of the complications also are associated with inadequate training in proper injection technique itself.[14],[15]

The most important complication of intramuscular injections (IM) was abscess formation and in one study, in 31% of patients who had developed complications.[14] The abscesses can either be pyogenic or sterile. Sterile abscesses seen in IM injections are composed of liquefied fat and muscle that occur as a consequence of necrosis of involved tissues. These abscesses are the results of hypersensitivity to the injected medication. This hypersensitivity is manifested by local tissue necrosis and liquefaction with a surrounding area of intense inflammation.[16],[17] A total of 85 injection site abscesses, of which 71 DPT vaccinations given in thigh and 14 BCG vaccinations given in arm, were included in the study. Among the DPT vaccination, 33 (46.5%) were sterile abscesses. It has been hypothesized that vaccines with adjuvants are the notorious risk factors for sterile abscess instead of improper storage, preparation, or administration of a vaccine.[18]

Pyogenic abscesses are usually caused by bacteria that enter during inoculation either from the needle syringe or medication. These bacteria gain access as a result of poor site preparation and are carried to tissues, thereby leading to the formation of infectious abscesses.[17] Among pyogenic abscesses, S. aureus has been most typically isolated for a very long time. Similarly in the current study, S. aureus was the major pathogen isolated in 33.8% (24) of the abscesses. The other organism isolated in our study was M. abscessus, 17% (12). Among the BCG postvaccination abscess M. bovis was isolated in 78.6% (11), S. aureus in 7% (1), and sterile in 14.2% (2). There is a scarcity of published literature to determine the prevalence of organisms in postvaccination abscess. Hence, further studies are needed for confirmation.

Postinjection cutaneous abscess due to RGM was first reported as early as 1938 by Da Costa Cruz.[19] M. abscessus is known to be a major cause of skin infections among the rapidly growing Mycobacterial species.[20] Inman et al.[21] in 1969 reported an outbreak amongst 12 patients who were treated at an ear, nose, and throat clinic by contaminated histamine injections. Galil et al.[22] reported on a multistate outbreak of postinjection abscesses related to the utilization of an unlicensed injectable product that was contaminated by mycobacterium. In our current study, M. abscessus was isolated in 17% of the abscesses.

Postinjection abscesses from RGM, including M. abscessus, have resulted from both intrinsic contamination nd extrinsic contamination of injectable drug preparations or injection equipment.[7] These bacteria have been increasingly recognized even from harsh environments (i.e., temperature extremes, low nutrients, and low pH). These hydrophobic organisms successfully survive by biofilm formation and their occurrence in early biofilms in water pipes may make them real biofilm “pioneers.” These RGM are difficult to eradicate with common decontamination practices and are relatively resistant (compared with coliforms) to standard disinfectants such as alkaline glutaraldehydes, chlorine, and organomercurials.[23] The probable hypothesis for the source of infection in our cases could be the organism would have been in the gluteal region after showering in water and not been decontaminated properly before injection. Contamination of vaccines is unlikely, as only sporadic cases were reported and not as an outbreak.

Post-BCG vaccination has relatively uncommon, local, or systemic side effects and is usually seen in cases of overdose, poor injection techniques, and fortuitous revaccination. Review of literature shows only rare cases.[24] In the current study, there have been ten babies with BCG lymphadenitis caused by M. bovis. If the injection is injected at the suggested sites (i.e., in deltoid) under sterile conditions and indicated dosage, then abscesses are relatively uncommon.[24]

A study by Yuan et al.[7] reported on M. abscessus causing postinjection abscess using nine cases with single injections, and the median incubation period was 31 days (range: 13–87 days). Similarly in our study, the median time between vaccine administration and onset of symptoms was 31.5 (ranging between 25 and 49) days in case of abscess due to M. abscessus. The mean incubation period was 50.4 days (ranging between 33 and 73 days) in case of M. bovis. A similar observation was noted in a case report by d'Aleo et al.[24] where postvaccination abscess by M. bovis developed 6 weeks later.

Cutaneous abscesses caused by M abscessus are usually localized in immunocompetent patients. Typical manifestations of a cutaneous abscess include cellulitis, nodules, ulceration plaques, and fistula formation, with tenderness or fluctuation.[25] Similarly, our entire postvaccination abscess presented with localized cellulitis or abscess formation. d'Aleo et al.[24] stated that rarely keloid formation and regional lymphadenitis may occur additionally to ulceration and abscess formation. However, seven among ten cases in our current study with post-BCG injection abscess had regional lymphadenitis together with local swelling and erythema.

Appropriate management of babies with M. abscessus depends on drug susceptibility testing (DST) performed by standard methodology. We performed DST as per CLSI guidelines. American Thoracic Society/Infectious Diseases Society of America guidelines usually recommend a combination of antibiotics supported in vitro results (CLSI).[10] Amikacin was found to inhibit all our RGM isolates that were tested, and similarly, all RGM were susceptible to clarithromycin, similar to the study by Kumar et al.[26] where all M. abscessus were susceptible to clarithromycin and amikacin. In our setting, treatment options for RGM infections would be a combination of two agents with in vitro activity and that may include amikacin[27] with clarithromycin.[28] All our cases with M abscessus were healed in 2–3 weeks duration and the drugs were continued yet one more week after clinical cure. All babies responded well and there were no sequelae. Unlike infection with surgical site infections where healing occurred only after months of therapy ranging from 3 months to 6 months, RGM in injection site abscess responded well in fewer weeks.

Management of babies with post-BCG abscess and lymphadenitis follows various recommendations. These vary from no treatment to incision and drainage, needle aspiration, treatment with drugs, or a combination of these. Some authors even believe that needle aspiration is an effective management of choice although this treatment is not effective and may require additional treatment.[22] All our babies with BCG abscess and regional lymphadenitis responded well with incision and drainage alone and did not require further drugs. This was similar to another study by d'Aleo et al.[24] where they treated the baby with gentamicin sulfate ointment locally who cured completely within 2 weeks without recurrence.


  Conclusion Top


Our study demonstrated an increased emergence of Mycobacterial spp from injection site abscess and the utmost necessity of aseptic precautions and proper cleaning of the injection site and in addition proper inoculation technique to prevent these abscess. M. bovis requires no treatment except for incision and drainage, whereas a combination of antibiotics as per the sensitivity report is essential for proper treatment of M. abscessus.

Ethical clearance

AVMC/IEC2016/007.

Acknowledgments

We thank the babies and their mothers who participated in the study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Treadwell T. Intramuscular injection site injuries masquerading as pressure ulcers. Wounds 2003;15:302-12.  Back to cited text no. 15
    
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Kwon YH, Lee GY, Kim WS, Kim KJ. A case of skin and soft tissue infection caused by Mycobacterium abscessus. Ann Dermatol 2009;21:84-7.  Back to cited text no. 20
    
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Chen X, Jin Y, Torres KM, Li B, Zhuo F, Ding X, et al. Mycobacterium abscessus cutaneous infection secondary to botulinum toxin injection: A report of 2 cases. JAAD Case Rep 2019;5:982-4.  Back to cited text no. 25
    
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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9]
 
 
    Tables

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