Clindamycin: An Effective Treatment for Granulomatous Mastitis Caused by Corynebacterium Kroppenstedtii in a Pregnant Patient.

Corynebacterium spp. are Gram-positive bacteria, and recent studies have proposed a potential link between granulomatous mastitis and Corynebacterium kroppenstedtii infections, posing a challenge in selecting appropriate antibiotics, particularly in pregnant women. A young pregnant woman presented with a palpable lump in her left breast. Subsequent assessment revealed the presence of necrotising granulomatous mastitis attributed to C. kroppenstedtii. Initially treated with amoxicillin/clavulanate, the patient showed no improvement. Consequently, clindamycin was administered based on culture and sensitivity results, which resulted in a favourable response with no recurrence of symptoms. This report aims to emphasise the efficacy of clindamycin as a treatment option for granulomatous mastitis caused by C. kroppenstedtii. LEARNING POINTS: Alternative antibiotics for treatment of granulomatous mastitis can be effective.The safety and efficacy of antibiotics in pregnancy is important.

Preliminary comparative genomics analysis among Corynebacterium kroppenstedtii complex necessitates a reassessment of precise species associated with mastitis.

AIMS: This study aimed to characterize the first complete genome of Corynebacterium parakroppenstedtii and clarify the evolutionary relationship in the Corynebacterium kroppenstedtii complex (CKC) by using comparative genomics analysis. METHODS AND RESULTS: The genome of isolate yu01 from a breast specimen was sequenced, and 35 CKC genomes were collected. Analysis of 16S rRNA, rpoB, and fusA suggested ambiguous identification, whereas ANI analysis assigned isolate yu01 as Coryne. parakroppenstedtii. The fourth genospecies "Corynebacterium aliikroppenstedtii" was identified in CKC. Comparative genomics analysis suggested that the genomic arrangement in CKC was highly conserved. A total of 43 potential virulence genes and 79 species-specific genes were detected. Most genome-based phylogenetic analysis were incapable of resolving the interspecific evolutionary relationships among CKCs. A total of 20 core genes were found to be distinguishable in CKC. CONCLUSIONS: This study suggested the limited divergence and unavailability of normal single gene-based identification in CKC and questioned the precise species of strains associated with mastitis, identified as Coryne. kroppenstedtii in previous studies. The 20 genes showed potential to enhance the methods for the identification and epidemiological investigation of CKC.

Granulomatous Mastitis Occurring during Pregnancy: A Case Report.

Background and Objectives: Granulomatous mastitis is a benign disease with a clinical presentation similar to that of breast cancer, and is most commonly observed in women of childbearing age. Although it has been suggested that autoimmune diseases are involved in its pathogenesis, no specific treatments have been established. The occurrence of this disease during pregnancy has rarely been reported. We presented the case of a 37-year-old woman who complained of left breast induration at 24 weeks' gestation. Materials and Methods: She was pregnant and manifested a dichorionic, diamniotic placenta. At 24 weeks of gestation, the patient experienced a sensation of hardness in her left breast. Mastitis was suspected, and she was treated with cephem antibiotics. Simultaneously, she was diagnosed with erythema nodosum in the extremities. As her symptoms did not improve, an incisional drainage was performed. Bacterial cultures were obtained at 31 weeks of gestation, and Corynebacterium kroppenstedtii was detected. Results: An elective cesarean section was performed at 37 weeks of gestation, and the baby was delivered safely. After delivery, a needle biopsy was performed, and the patient was diagnosed with granulomatous mastitis. She was completely cured with prednisolone after weaning. In this case, the patient's condition was maintained through incision and drainage, as well as antibiotic, anti-inflammatory, and analgesic drugs during pregnancy. This approach was chosen, taking into consideration the potential side effects of steroids. Conclusions: This case suggests that incisional drainage and antibiotic therapy, as well as steroids and surgery, may be considered in the treatment of granulomatous mastitis occurring during pregnancy. This may also be true for management during delivery. After delivery, breastfeeding and steroidal therapy proved to be effective in treating the condition.

Clinical characteristics and therapeutic strategy of granulomatous mastitis accompanied by Corynebacterium kroppenstedtii: a retrospective cohort study.

BACKGROUND: Increasing evidence has suggested that Corynebacterium kroppenstedtii is associated with some cases of granulomatous mastitis, mostly based on pathology or microbiology. We aimed to identify the clinical characteristics and treatment regimens for granulomatous mastitis with Corynebacterium kroppenstedtii infection. Understanding these clinical features is essential for patient care. METHODS: We retrospectively collected data on 201 patients who were pathologically diagnosed with granulomatous mastitis and had microbiological results of either Corynebacterium kroppenstedtii or no bacterial growth and recorded and analysed their demographics, clinical characteristics, and clinical outcomes. RESULTS: There were 107 patients in the CK group and 94 patients in the negative group. Sinus formation (x2 = 13.028, p = 0.000), time to complete remission at the first treatment period (Z = -3.027, p = 0.002), diameter of breast mass at first-time medical consultancy (Z = -2.539, p = 0.011) and recurrence (x2 = 4.953, p = 0.026) were statistically significant. Age (Z = -1.046, p = 0.295), laterality (x2 = 4.217, p = 0.121), time to presentation since the last delivery (x2 = 0.028, p = 0.868), BMI (Z = -0.947, p = 0.344), lactation time (Z = -1.378, p = 0.168), parity (x2 = 1.799, p = 0.180), gravida (Z = -0.144, p = 0.885), history of lactational mastitis or abscess (x2 = 0.115, p = 0.734), local trauma (x2 = 0.982, p = 0.322), hyperprolactinemia (x2 = 0.706, p = 0.401), erythema nodosum (x2 = 0.292, p = 0.589), and nipple discharge (x2 = 0.281, p = 0.596) did not demonstrate statistical significance. Regarding recurrence related to therapeutic strategy, except for surgery combined with immunosuppressants (x2 = 9.110, p = 0.003), which was statistically significant, none of the other treatment regimens reached statistical significance. The recurrence rate of patients in the CK group using rifampicin in their treatment course was 22.0% (x2 = 4.892, p = 0.027). CONCLUSIONS: Granulomatous mastitis accompanied by Corynebacterium kroppenstedtii more easily forms sinuses and has a higher recurrence rate. Both of the clinical characteristics may indicate that Corynebacterium kroppenstedtii plays an important role in the development and progression of granulomatous mastitis. Lipophilic antibiotics may be essential for granulomatous mastitis with Corynebacterium kroppenstedtii infection.

Clinical characteristics and microbiota analysis of 44 patients with granulomatous mastitis.

Introduction: Granulomatous mastitis (GM) is a chronic inflammatory breast disease. In recent years, the role of Corynebacterium in GM onset has received more and more attention. This study aims to detect the dominant bacterium in GM patients and analyze the association between clinical characteristics and infectious factors. Methods: In this study, 88 samples from 44 GM patients, six acute lactation mastitis (ALM) patients, and 25 non-inflammatory breast disease (NIB) patients were divided into a GM pus group, a GM tissue group, an ALM pus group, and a NIB tissue group; then, 16S ribosomal DNA sequencing was used to explore their microbiota. The clinical data of all 44 GM patients were also retrospectively collected and analyzed to determine their relationship with infection. Results: The median age of the 44 GM patients was 33 years, and 88.6% of patients had primary-onset cases, while 11.4% were recurrences; additionally, 89.5% of patients were postpartum and 10.5% were nulliparous. The serum prolactin level was abnormal in nine patients (24.3%). Samples from 15 GM patients (34.1%) had a Corynebacterium abundance of >1% (1.08-80.08%), with eight (53.3%) displaying an abundance of >10%. Corynebacterium was the only genus with significant differences between the GM pus group and the other three groups (p < 0.05). Corynebacterium kroppenstedtii was the predominant Corynebacterium species. Among clinical characteristics, a statistical difference in breast abscess formation was observed according to Corynebacterium abundance in Corynebacterium-positive and- negative patients (p < 0.05). Discussion: This study explored the relationship between Corynebacterium infection and GM, compared the clinical characteristics between Corynebacterium-positive and- negative patients, and provided support for the role of Corynebacterium species-in particular, C. kroppenstedtii-in the pathogenesis of GM. The detection of Corynebacterium can predict GM onset, especially in patients with high prolactin levels or a history of recent lactation.

Clinical features and recurrence of Corynebacterium kroppenstedtii infection in patients with mastitis.

BACKGROUND: Few studies have investigated the differences in clinical features of patients with mastitis following Corynebacterium kroppenstedtii infection, and most focused on the bacterial antimicrobial susceptibility, detection methods and therapy. METHODOLOGY: There were 133 patients with mastitis infected by C. kroppenstedtii between August 2016 and September 2019. C. kroppenstedtii was identified using mass spectrometry. The demographics, clinical diagnosis, laboratory test results of different types of mastitis combined with bacillus infection, and the effects of different treatments in reducing recurrence were compared. RESULTS: The incidence of pus following C. kroppenstedtii infection was higher in patients with non-granulomatous lobular mastitis (NGLM; 56.6%) than in those with granulomatous lobular mastitis (GLM; 33.3%; χ2 = 7.072, p = 0.008). While C-reactive protein (CRP) was higher in the GLM group (12.50 mg/L) than in the NGLM group (6.05 mg/L; Z = - 2.187, p = 0.029). Treatment with local lavage (triamcinolone acetonide) and antibiotics (cefuroxime) showed a recurrent rate of 25.9% in C. kroppenstedtii infection. CONCLUSION: Increased pus, large masses, and an elevated CRP level may occur in patients with mastitis infected by C.kroppenstedtii. These clinical features may guide the determination of the bacterial infection in patients with mastitis. Combining an antibiotic with a triamcinolone acetonide lavage, preferably cefuroxime, may reduce the recurrence.

New Insights of Corynebacterium kroppenstedtii in Granulomatous Lobular Mastitis based on Nanopore Sequencing.

BACKGROUND: The etiology of granulomatous lobular mastitis (GLM) remains unknown. This study aimed to detect bacteria in GLM using Nanopore sequencing and identify the relationship between GLM and Corynebacterium kroppenstedtii. METHODS AND MATERIALS: The bacterial detection on fresh samples (including breast pus and tissue) of 50 GLM patients using nanopore sequencing and culture methods. The bacterial detection rate of participants with different stages were compared and analyzed. Formalin-fixed and paraffin-embedded (FFPE) tissues from 39 patients were performed on Gram staining to identify Gram-positive bacilli (GPB) within lipid vacuoles. Moreover, the clinicopathological characteristics of GLM patients in different bacterial subgroups were also conducted. RESULTS: In 50 GLM patients, the detection rate of bacteria was 78% using nanopore sequencing method, especially in the early stage of GLM (over 80%), which was significantly higher than that using culture methods (24%, p < 0.001). The dominant bacteria were Corynebacterium species (64%), especially for the Corynebacterium kroppenstedtii. The detection rate of C. kroppenstedtii in nanopore sequencing method (56%) was higher than that in culture methods (16%, p < 0.001). Gram staining positive of bacteria in 7 patients, and 5 of them were C. kroppenstedtii. Thirty-one patients (31/39, 79.5%) exhibited typical histological structure of cystic neutrophilic granulomatous mastitis (CNGM), and eighteen patients detected with C. kroppenstedtii. CONCLUSION: Nanopore sequencing showed rapid and accurate bacteria detection over culture method in GLM patients. GLM is not sterile inflammation and closely related to C. kroppenstedtii. CNGM was associated with Corynebacterium infection, especially for C. kroppenstedtii.

Corynebacterium kroppenstedtii breast abscesses in context, a retrospective cohort study.

Corynebacterium kroppenstedtii breast abscesses and granulomatous mastitis have gained increased recognition in the 20 years since their association was first described. No studies to date have described this organism in the context of all breast abscess pathogens. We retrospectively reviewed 160 community-acquired breast abscess samples from 135 patients in a 3 year period, describing the organisms isolated along with risk factors, site of infection and outcomes. We compared patient subgroups with acute and chronic abscesses, the latter defined as having a requirement for repeat aspiration more than 1 month apart. The prevalence of C. kroppenstedtii breast abscesses was 8 % in all patients (11/135), rising to 32 % in chronic abscesses (10/31), but only 1 % in acute abscesses (1/104; P<0.01). Only 10 % (1/10) of patients with C. kroppenstedtii chronic abscesses were smokers, whereas 75 % of patients (15/20) with non-C. kroppenstedtii chronic abscesses were smokers (P=0.01). C. kroppenstedtii should be considered in recurrent and prolonged infections, especially in non-smokers, and diagnostic methods altered accordingly. Identifying C. kroppenstedtii provides diagnostic clarity and alters management with recommendations for longer courses of treatment using non-beta-lactam antibiotics.

A novel therapy for granulomatous lobular mastitis: Local heat therapy.

Granulomatous lobular mastitis (GLM) is a chronic inflammatory breast condition that is characterized by granulomatous inflammation. GLM remains a refractory disease due to its failure to respond to routine anti-inflammatory therapies and its high recurrence rate. Thus, the present study aimed to investigate the application of local heat therapy in GLM as a potential therapeutic strategy. The results revealed that the application of local heat therapy was associated with a shortened remission time for GLM, while the remission and recurrence rates were similar to those of existing therapies. The median first remission time following local heat therapy was significantly decreased compared with that following corticosteroid therapy (5.30 months vs. 11.27 months; P<0.05). The remission rates were not significantly different between the local heat therapy (76.9%), extensive excision (90.4%) and the corticosteroid therapy (85.7%) groups (P>0.05). In addition, the recurrence rates were not statistically different between the groups (local heat therapy, 8.3%; extensive excision, 10%; and corticosteroid therapy, 10%; P>0.05). The local heat therapy showed mild adverse effects and shortened healing times compared to the other therapies; however, further confirmation is required.

Corynebacterium kroppenstedtii y patología mamaria / Corynebacterium kroppenstedtii and breast pathology

Resumen Corynebacterium kroppenstedtii es un bacilo gram positivo corineforme lipofílico, poco frecuente en la clínica humana. Forma parte de la microbiota cutánea de los seres humanos y, por esta razón, su interpretación clínica es compleja. La mastitis granulomatosa es una enfermedad inflamatoria de origen incierto con baja incidencia. Se presentan dos casos clínicos en los que se describe la asociación de C. kroppenstedtii con mastitis granulomatosa. El tejido mamario es rico en lípidos. El carácter lipofílico de este microorganismo podría explicar su presencia en dicho tejido.

Abstract Corynebacterium kroppenstedtii is a rare lipophilic coryneform gram-positive bacillus. It is part of the human skin microbiota and, for this reason, its clinical interpretation is complex. Granulomatous mastitis is an inflammatory disease of uncertain origin with a low incidence. The association of C. kroppenstedtii with granulomatous mastitis was described in two clinical case reports. The lipophilic characteristics of this microorganism explains why it can be found in lipid-rich breast tissue.

Resumo Corynebacterium kroppenstedtii é um bacilo gram-positivo corineforme lipofílico poco frecuente. Faz parte da microbiota do seres humanos, por isso sua interpretação clínica é complexa. A mastite granulomatosa é uma doença inflamatória de origem incerta com baixa incidência. Foram apresentados dois casos clínicos nos quais é descrita a associação de C. kroppenstedtii com mastite granulomatosa. O tecido mamário é rico em lipídios. O caráter lipofílico desse microrganismo pode explicar sua presença em tal tecido.

[Corynebacterium kroppenstedtii breast infections: Report of four cases]. / Infecciones mamarias por Corynebacterium kroppenstedtii: comunicación de 4 casos.

Corynebacterium kroppenstedtii is an immobile, non-sporulated, glucose-fermenting and lipophilic gram-positive rod of the skin microbiota. In recent years, numerous isolates of this species have been reported mainly in breast infections, such as abscesses and granulomatous mastitis. We present here four cases of C. kroppenstedtii infections isolated from breast aspiration samples in women. C. kroppenstedtii was identified by conventional methodology and mass spectrometry (MALDI-TOF MS). Using the epsilometric method, these isolates showed susceptibility to penicillin, ceftriaxone, minocycline, ciprofloxacin, and vancomycin, and variable susceptibility to clindamycin and trimethoprim sulfamethoxazole. Due to the association of C. kroppenstedtii with mammary infections, the identification at the species level of those corynebacteria isolated from this location is highly advisable in order to reach the final diagnosis and to test the antimicrobial susceptibility in order to apply the appropriate antibiotic treatment.

Cystic Neutrophilic Granulomatous Mastitis: A Clinicopathological Study With 16s rRNA Sequencing for the Detection of Corynebacteria in Formalin-Fixed Paraffin-Embedded Tissue.

Cystic neutrophilic granulomatous mastitis (CNGM) is a histologically characterized variant of granulomatous lobular mastitis that is associated with lipophilic Corynebacterium species. It remains a largely underrecognized entity in India. Our aim was to study CNGM in the Asian Indian population and explore if 16s rRNA sequencing could be used on formalin-fixed paraffin-embedded (FFPE) tissue to identify the causative organism. We studied 24 cases with histological features of CNGM with hematoxylin and eosin, Gram, Ziehl-Neelsen, and Periodic acid-Schiff stains. Tuberculosis-polymerase chain reaction and 16s rRNA gene sequencing on DNA extracted from FFPE was attempted (N = 23). Gram-positive bacilli were seen in 20/24 cases. Routine culture with prolonged incubation yielded Corynebacterium species in 8 cases; 7 of these cases were evaluated by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for species identification. C matruchotti was identified in one case by BD Phoenix. MALDI-TOF MS identified the remaining 7 cases as C kroppenstedtii (N = 4) and C tuberculostearicum (N = 2), with no identification in one. Corynebacteria were identified by 16s rRNA sequencing on DNA extracted from FFPE in 12/23 cases using a primer targeting the V5-V6 region that was found to be more conserved in Corynebacterium species. All cases were negative for the diagnosis of tuberculosis. CNGM can be identified by routine stains. Culture using routine media with prolonged incubation is often adequate to isolate the organism. 16s rRNA sequencing on DNA extracted from FFPE tissue can help make an etiological diagnosis in some cases where only paraffin blocks are available.

Corynebacterium kroppenstedtii as a pathogen of a Jones tube infection following conjunctivo-dacryocystorhinostomy.

A 35-year-old woman complained of an unpleasant odor for a few days after a change in foundation cream. The patient had previously undergone conjunctivo-dacryocystorhinostomy with a Jones tube fixed with non-absorbable suture. Slit-lamp examination revealed an orange-colored discharge in the tube. A culture test of the discharge showed Corynebacterium kroppenstedtii (1+), Aspergillus versicolor (1+), and Mycobacterium chelonae (1+). After medical treatment and suture removal, the discharge completely disappeared. This is the first reported case of a Jones tube infection following conjunctivo-dacryocystorhinostomy with multiple microorganisms, including C. kroppenstedtii.

Corynebacterium kroppenstedtii in granulomatous mastitis: Analysis of formalin-fixed, paraffin-embedded biopsy specimens by immunostaining using low-specificity bacterial antisera and real-time polymerase chain reaction.

Granulomatous mastitis (GM) is a rare inflammatory disease of the post-lactation breast, clinically mimicking breast cancer. GM is microscopically characterized by formation of epithelioid granulomas and abscess (suppurative granulomas) with lipid droplet-centered inflammation. Corynebacterium kroppenstedtii (Ck) is known as a causative bacterium of GM, and identification of Ck infection within the lesion should thus be essential for confirming the diagnosis. In the present study, we analyzed formalin-fixed, paraffin-embedded (FFPE) biopsy specimens of a total of 18 GM lesions with immunostaining and real-time PCR for Ck genome. Widely cross-reactive rabbit antisera against Bacillus Calmette-Guerin (BCG), Bacillus cereus, Treponema pallidum and Escherichia coli were chosen. With real-time PCR, Ck genome was demonstrated in 7 of 18 GM lesions. Immunohistochemically, the low-specificity antisera reacted with the cytoplasm of phagocytes and/or granuloma-engulfed lipid droplets in 12 of 18 GM lesions. Antigenic positivity was observed in the following order: BCG > B. cereus > T. pallidum > E. coli. Real-time PCR using DNA extracted from FFPE sections was useful but not consistent for identifying the Ck genome in GM, while immunostaining using cross-reactive antisera against four kinds of bacteria was not Ck-specific but was applicable to visualizing bacterial infection within the GM lesions.

Corynebacterium kroppenstedtii Is an Emerging Cause of Mastitis Especially in Patients With Psychiatric Illness on Antipsychotic Medication.

This retrospective study of patients with Corynebacterium kroppenstedtii infections revealed a predominance of mastitis and a potential association with psychiatric illnesses. At least one third of our patients with C kroppenstedtii mastitis had psychiatric illness, and >92% received antipsychotic medications. Drug-induced hyperprolactinemia may be an important modifiable risk factor in these patients.

Cystic neutrophilic granulomatous mastitis associated with Corynebacterium including Corynebacterium kroppenstedtii.

Granulomatous (lobular) mastitis is a rare inflammatory breast disease affecting parous reproductive-aged women. Once considered idiopathic, there is growing evidence of an association with corynebacteria infection, especially in the setting of a distinct histological pattern termed cystic neutrophilic granulomatous mastitis (CNGM). We describe 15 cases with histological features either confirming (n = 12) or suggesting (n = 3) CNGM, and concurrent microbiological evidence of Corynebacterium species. The organism was detected by culture or 16S rRNA gene sequencing of specimens obtained at surgery or fine needle aspiration. In seven cases, Gram-positive organisms were seen within vacuolated spaces. Speciation was performed in nine cases, with Corynebacterium kroppenstedtii subsequently identified. These cases provide further evidence in support of this association and in doing so highlight the importance of recognising these histological clues as well as the limitations of Gram stain and microbiological culture in detecting this previously under-recognised disease process.

Characterization and antimicrobial susceptibility of one antibiotic-sensitive and one multidrug-resistant Corynebacterium kroppenstedtii strain isolated from patients with granulomatous mastitis.

Human infections associated with Corynebacterium kroppenstedtii are rarely reported, and this organism is usually described as antibiotic sensitive. Almost all published cases of C. kroppenstedtii infections have been associated with breast pathology in women and have been described in New Zealand, France, Canada, India and Japan. Here we describe the microbiologic characteristics of two strains isolated from two women diagnosed of granulomatous mastitis in Spain. One C. kroppenstedtii isolate was antibiotic sensitive while the other was multidrug resistant. Biochemical identification was possible using a wide battery of methods including API Coryne V2.0, API Strep, API NH, API NE, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and 16S rRNA gene amplification and sequencing. Antimicrobial susceptibility to 28 antibiotics as determined by Etest showed one isolate being sensitive to benzylpenicillin, ciprofloxacin, moxifloxacin, gentamicin, vancomycin, clindamycin, tetracycline, linezolid and rifampin. The second isolate showed resistance to ciprofloxacin, moxifloxacin, clindamycin, tetracycline and rifampin. The multidrug-resistant isolate contained the erm(X), tet(W), cmx, aphA1-IAB, strAB and sul1 resistance genes known from the R plasmid pJA144188 of Corynebacterium resistens. These genes were absent in the genome of the antibiotic-sensitive isolate. This report confirms the tropism of this microorganism for women's breasts and presents the first description of a multidrug-resistant C. kroppenstedtii strain.

A microbiological and clinical review on Corynebacterium kroppenstedtii.

The genus Corynebacterium represents a taxon of Gram-positive bacteria with a high G+C content in the genomic DNA. Corynebacterium kroppenstedtii is an unusual member of this taxon as it lacks the characteristic mycolic acids in the cell envelope. Genome sequence analysis of the C. kroppenstedtii type strain has revealed a lipophilic (lipid-requiring) lifestyle and a remarkable repertoire of carbohydrate uptake and utilization systems. Clinical isolates of C. kroppenstedtii have been obtained almost exclusively from female patients and mainly from breast abscesses and cases of granulomatous mastitis. However, the role of C. kroppenstedtii in breast pathologies remains unclear. This review provides a comprehensive overview of the taxonomy, microbiology, and microbiological identification of C. kroppenstedtii, including polyphasic phenotypic approaches, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and the use of 16S rRNA gene sequencing. A clinical review presents reported cases, various antimicrobial treatments, antibiotic susceptibility assays, and antibiotic resistance genes detected during genome sequencing. C. kroppenstedtii must be considered a potential opportunistic human pathogen and should be identified accurately in clinical laboratories.

Early prosthetic valve endocarditis caused by Corynebacterium kroppenstedtii.

Corynebacterium (C.) kroppenstedtii is a rarely detected agent of bacterial infections in humans. Here, we describe the first case of prosthetic valve endocarditis caused by C. kroppenstedtii. Application of molecular methods using surgically excised valve tissue was a cornerstone for the establishment of the microbiological diagnosis, which is crucial for targeted antimicrobial treatment.