{"paper_id":"981ffb68-b480-44fe-a7d9-b8f350299fcb","body_text":"Fast-growing mycobacteria (FGM) or mycobacteria non-tuberculous (MNT), have emerged\nas important human pathogens causing a variety of illnesses, such as post-traumatic\ninfections and post-surgical disseminated skin diseases. These mycobacteria are\nwidely spread in the environment, mainly in water. These microorganisms can\ncontaminate medical equipment and have been responsible for several outbreaks of\nhealthcare-associated infections \n 1 \n , but so far, there is no evidence of person-to-person transmission \n 2 \n .\nTheir occurrence has been frequently reported in surgeries of aesthetic procedures,\nbut also in videolaparoscopies \n 3 \n  and secondary to the use of catheters \n 4 \n . The nosocomial outbreaks recorded in Brazil are related to failures in\ncleaning processes of medical products \n 5 \n .\nThe prevalence of FGM infection is increasingly common in clinical practice and might\nbe related to immune system deficiencies \n 2 \n . When it comes to the extrapulmonary disease, skin and subcutaneous tissue\ninfections are commonly caused by other types of mycobacterium \n 1 \n \n , \n \n 6 \n .\n\nWe report the case of a 37 years old woman who sought the Infectious and Parasitic\nDiseases (IPD) Clinic, Hospital das Clinicas (HC), Universidade Federal de\nPernambuco (UFPE), Pernambuco State, Brazil, four months after a caesarean section,\npresenting with difficulties in healing and local pain outside the surgical\nsite.\nShe reported severe pain during the first month after surgery in a hardened palpation\narea, above the surgical incision, and on the right side of her pelvis. The\nobstetric gynecologist prescribed the anti-inflammatory nimesulide 50 mg, the\nantibiotic cephalexin 500 mg for 10 days, and an ultrasound examination (USG).\nThe result of the 1 st  USG suggested the presence of two granulomas, one on\nthe right side of the surgical scar, within the subcutaneous tissue, corresponding\nto a rounded, echogenic image, without Doppler flow, measuring 1.0 × 0.9 cm and the\nother with the same characteristics, between the surgical and umbilical scar,\nlocated within the musculature, measuring 1.3 × 0.8 cm.\nThe gynecologist interpreted the results as a probable rejection of the unabsorbed\nsutures and advised the patient to look for the medical doctor responsible for\nperforming the elective stitch removal surgery or waiting for the stiches to be\ncompletely absorbed.\nThe attending physician suggested an additional USG that showed an elongated\nhyperechoic area with a hypoechoic halo within the superficial muscular plane in the\nright pelvic region, which could correspond to a cicatricial fibrosis. The physician\nrecommended waiting for the resorption of sutures in order to prevent the patient\nfrom undergoing another surgery.\nAccording to the physician, multifilament synthetic absorbable thread was used in the\naponeuroses. In the subcutaneous tissue, the suture was made with a simple Cut-gut 0\nmultifilament natural absorbable thread, and in the skin a synthetic monofilament\nthread was used. However, after the end of drug treatment and before the wires were\nreabsorbed, the region began to show redness, intense pain and a greater hardening\nof palpation, as well as local burning ( Figure\n1A ).\nAs conditions worsened, the patient sought gynecological help and had a\n3 rd  USG that observed a liquid, hypoechoic collection in the\nsubcutaneous tissue forming a fistulous path towards the skin. There was also the\npresence of a hyperechogenic tubuliform halo adjacent to the liquid collection\nextending to the superficial muscular plane, measuring 3.2 cm in length and 0.6 cm\nin thickness, characterized as a fibrotic tissue.\nEvery time she stopped the anti-inflammatory drug, she had pain returned and she\nsought a gynecological help again. The doctor decided to make a small incision at\nthe site and found the presence of a purulent exudate, suggesting an abscess. A\ndrain was placed for 3 days, Ciprofloxacin 500 mg for 10 days and Nimesulide 50 mg\nfor 5 days were prescribed. The incision made for drainage healed within 18 days\n( Figure 1B ) as well as the right corner of\nthe cesarean section.\nHowever, 24 days after the drainage, she reported having the same symptoms, but this\ntime on the left side, close to the navel. Finally, she turned to the doctor to\ndiscuss possible causes, including some type of allergic reaction to sutures, seroma\nor post-cesarean endometriosis. Considering that she had a problem related to\nhealing, she was referred to a plastic surgeon and then to an infectious disease\nspecialist due to a new amamnesis and the lack of response to treatment, possibly\ncaused by a resistant microorganism.\nAfter five months without an accurate diagnosis and after reviewing the tests\nperformed, the infectious disease specialist told the patient that she had an\ninfection most likely due to FGM. During this time, more USG, blood and urine tests\nwere performed to assess her renal and hepatic functions.\nAll blood and urine tests results were within normalranges. . Nonetheless, the new\nUSG revealed that at the first drainage site there was a collection together with\nand inflammatory process and a fistulous tract that deepened to the muscular\naponeurosis ( Figure 2A ). On the left of the\nalba line, there was a collection and a fistulous pathway that deepened to the\nmuscular aponeurosis near the fistula reported previously, but without a deeper\ncollection ( Figure 2B ).\nBased on the clinical signs, recent USG data, and non-response to the conventional\nantibiotic therapy prescribed, an empirical treatment for FGM was started. To this\nend, 500 mg of oral clarithromycin was prescribed every 12 h for a period of one\nyear. Surgery was performed for debridement and sample collection (subcutaneous\ntissue for histopathology and exudate for culture). Amikacin 1g/dose three times a\nweek intravenously was administered for a period of six months beginning on the day\nof surgery and periodically maintained at the IPD/UFPE.\nThe histopathological analysis of hematoxylin-eosin (HE)-stained tissue fragments\nrevealed a chronic inflammatory process with the presence of tuberculoid granulomas\ncomposed of epithelioid cell clusters, surrounded by lymphocytes, permeated by\nneutrophils and occasionally by multinucleated giant cells ( Figure 3 ). During the Ziehl-Nieelsen testing, no bacilli were\nidentified. Microbiological tests were negative for both, bacterial and mycological\ncultures.\nBecause the culture did not show mycobacterial species, the paraffin-embedded tissues\nwere extracted and underwent a real-time PCR at the Oswaldo Cruz/UFPE Foundation's\nAggeu Magalhaes-CPqAM Research Center's Immunoepidemiology Laboratory. The\nmicroorganism identified belonged to the species  Micobacterium\nfortuitum .\nDuring the combined antibiotic therapy with injectable amikacin and oral\nclarithromycin, the patient showed a considerable clinical improvement, without new\nfoci or recurrences of hard nodules. After one month of treatment, the USG did not\nreveal the presence of new collections or fistulas in the subcutaneous tissue. By\nthe 4 th  month of treatment, fistulas were closing and the patient\nreported skin hypersentivity on the affected region, as well as mild pain.\nAfter six months, amikacin was discontinued, but clarithromycin continued for a year.\nDuring the six months of combined treatment, blood and urine tests revealed no\nchanges. However, the audiometry testing performed at the beginning and at the end\nof treatment showed a slight loss of hearing. The patient reported that after the\n4 th  month of treatment she started to have sporadic tinnitus in ears.\nAfter the end of the combined therapy, the patient continued without relapses and\nthe last two USG found no collections but showed the healing of fistulas. The\npatient will remain under observation for another year.\n\nDiseases caused by FGM on skin or soft tissues usually present with signs and\nsymptoms of inflammation. The incubation period may vary from one week to two\nyears \n 6 \n . Fever is rare and drainage may be purulent, usually odorless and colorless,\nresembling a sterile seroma. Patients do not respond to conventional antibiotic\ntherapy, leading to delayed diagnoses \n 7 \n .\nFGM are capable of biofilm formation directly linked to a greater persistence of\nthese pathogens in the environment \n 8 \n . The species are commonly found in nosocomial skin and soft tissue\ninfections, mainly in aesthetic procedures \n 3 \n \n , \n \n 9 \n . This explains why the plastic surgeon suspected a resistant microorganism\ninfection and referred the patient to an infectious disease specialist.\nInfections caused by FGM are not considered a public health problem. Therefore, their\nreporting is not mandatory, although some species are highly pathogenic and are\nresponsible for diseases and deaths \n 10 \n . FGM infections have emerged as an important cause of hospital-acquired\nsurgical site infection causing great morbidity and mortality. They are poorly\ndescribed in the literature in cesarean sections and in clinical practice, being\ncommonly associated to surgical site infections \n 11 \n . These factors may have contributed to a lengthy diagnosis.\nIt was not possible to trace the source of the infection. FGMs do not easily\npenetrate the host tissues, and that is why they are related to post-trauma\ninfections or after invasive procedures. These bacteria can survive and reproduce\nover a broad spectrum of pH, temperature, salinity and oxygen availability. In\naddition, many FGMs do not respond well to routinely used disinfectants \n 12 \n .\nThe pathogenesis of FGM is mediated by T lymphocytes. Their spread is usually due to\nimmune system deficiencies associated to reduced levels of interleukin-12 and\ninterferon-gamma \n 13 \n . The patient was HIV-negative and her leukocyte parameters were normal.\nHowever, during pregnancy there are many hormonal and steroids changes modulating\nthe immune response. Several studies have shown that suppression of the\nimmunocellular system occurs during pregnancy to prevent fetal rejection by\nincreasing estrogen and/or progesterone levels, especially the latter which\nincreases the synthesis of proinflammatory cytokines \n 14 \n . Therefore, it is suggested that the gestational and post-gestational period\nmay have made the patient temporarily more susceptible.\nIn clinical practice of gynecology and obstetrics, absorbable and nonabsorbable,\nmonofilament and multifilament sutures are used. Cutgut thread can cause many tissue\nreactions and have an unpredictable absorption time \n 15 \n . As sutures were not found, it was not possible to prove that they were the\nsource of the infection.\nEven with negative results from the main form of diagnosis, a patient who underwent\ninvasive procedures and presents with two or more signs of a compatible\nsymptomatology such as hyperemia, edema for more than a week, hard to heal\nerythematous lesions, nodular lesions with or without secretion drainage, fistulas,\nulcerations, hot or cold abscess, non-response to conventional antimicrobial\ntreatments should begin FGM-specific antimicrobials. Except for hyperemia, the\npatient in question presented with all clinical signs referred by the National\nHealth Surveillance Agency (ANVISA)technical note \n 5 \n  and only responded to specific treatment for fast-growing mycobacteria.\nThe time between the collection of material (exudate) and the arrival at the\nlaboratory, at room temperature, should not exceed one hour for the culture of FGM.\nIf a longer time is required, the sample should be transported in a Styrofoam\ncontainer, insulated in a plastic bag, kept refrigerated at 2-8 °C for up to 72\nh \n 16 \n . The sample (exudate) was only taken to the lab 5 h after collection in an\nice bag and this may have compromised the viability of FGM.\nUSG, magnetic resonance imaging, tomography and histopathological exams are the most\nrecommended tools for diagnosis of FGM. Regarding the therapeutic scheme, it should\ninclude surgery for debridement and antibiotic therapy \n 5 \n \n , \n \n 16 \n . In case of negative cultures, but with the presence of granulomas in the\nhistopathological examination, the patient should be prescribed clarithromycin for\nsix months and amikacin three times a week for 1-2 months, that may be extended up\nto six months.\nThe histopathological findings caused by FGM are chronic granulomatous inflammatory\nlesions and necrotizing granulomas with epithelioid cells, histiocytes and giant\ncells \n 5 \n . Because it fit the histopathological conditions described above, as well as\npresenting withhyperemia, hyperthemia, fistulas, collection and more than one\nlesion, even being immunocompetent, we opted for the extended treatment for this\npatient.\nMolecular examinations, such as RT-PCR, are another option for identifying FGM\nspecies and differentiating them from the  Mycobacterium\ntuberculosis  complex \n 17 \n  and in the case of this patient, the species was only identified using this\nmethod.\nTreatment for FGM is often complicated due to the side effects of antibiotic therapy,\nespecially the amikacin ototoxicity \n 18 \n . Normally, aminoglycosides predominantly affect a portion of the inner ear,\nthe cochlear and labyrinth hair cells, which may cause permanent hearing loss or\ntinnitus secondary to the degeneration of cochlear sensory hair cells. There may\nalso be dizziness or imbalance as a result of damage to the sensory structures of\nthe vestibular system \n 19 \n . According to the audiometry exams, the patient had no significant hearing\nloss, just sporadic tinnitus.\nThe most important aspect in mycobacterial infections is their prevention. There is\nneed for a rigorous care in cleaning and sterilizing material after surgical\nprocedures.  M. fortuitum  and  M. chelonae  strains\nare resistant to various disinfectants, including polyvinylpyrolidone (PVPI),\nformaldehyde and glutaraldehyde \n 5 \n .\n\nIt is of extreme importance to share these occurrences with gynecological-obstetric\nspecialists. A multidisciplinary team can assist in a faster and more accurate\ndiagnosis, saving the patient from prolonged suffering in both psychological and\npathophysiological aspects related to the toxicity of long-term medications.","source_license":"CC-BY-4.0","license_restricted":false}