Associations of fecal microbial profiles with breast cancer and nonmalignant breast disease in the Ghana Breast Health Study.

The gut microbiota may play a role in breast cancer etiology by regulating hormonal, metabolic and immunologic pathways. We investigated associations of fecal bacteria with breast cancer and nonmalignant breast disease in a case-control study conducted in Ghana, a country with rising breast cancer incidence and mortality. To do this, we sequenced the V4 region of the 16S rRNA gene to characterize bacteria in fecal samples collected at the time of breast biopsy (N = 379 breast cancer cases, N = 102 nonmalignant breast disease cases, N = 414 population-based controls). We estimated associations of alpha diversity (observed amplicon sequence variants [ASVs], Shannon index, and Faith's phylogenetic diversity), beta diversity (Bray-Curtis and unweighted/weighted UniFrac distance), and the presence and relative abundance of select taxa with breast cancer and nonmalignant breast disease using multivariable unconditional polytomous logistic regression. All alpha diversity metrics were strongly, inversely associated with odds of breast cancer and for those in the highest relative to lowest tertile of observed ASVs, the odds ratio (95% confidence interval) was 0.21 (0.13-0.36; Ptrend < .001). Alpha diversity associations were similar for nonmalignant breast disease and breast cancer grade/molecular subtype. All beta diversity distance matrices and multiple taxa with possible estrogen-conjugating and immune-related functions were strongly associated with breast cancer (all Ps < .001). There were no statistically significant differences between breast cancer and nonmalignant breast disease cases in any microbiota metric. In conclusion, fecal bacterial characteristics were strongly and similarly associated with breast cancer and nonmalignant breast disease. Our findings provide novel insight into potential microbially-mediated mechanisms of breast disease.

Characterization of Pediatric Breast Abscesses and Optimal Treatment: A Retrospective Analysis.

BACKGROUND: Literature on pediatric breast abscesses is sparse; therefore, treatment is based on adult literature which has shifted from incision and drainage (I&D) to needle aspiration. However, children may require different treatment due to different risk factors and the presence of a developing breast bud. We sought to characterize pediatric breast abscesses and compare outcomes. MATERIALS AND METHODS: A retrospective review of patients presenting with a primary breast abscess from January 2008 to December 2018 was conducted. Primary outcome was persistent disease. Antibiotic utilization, treatment required, and risk factors for abscess and recurrence were also assessed. A follow-up survey regarding scarring, deformity, and further procedures was administered. Fisher's exact and Kruskal-Wallis tests for group comparisons and multivariable regression to determine associations with recurrence were performed. RESULTS: Ninety-six patients were included. The median age was 12.8 y [IQR 4.9, 14.3], 81% were women, and 51% were African-American. Most commonly, patients were treated with antibiotics alone (47%), followed by I&D (27%), and aspiration (26%). Twelve patients (13%) had persistent disease. There was no difference in demographic or clinical characteristics between those with persistent disease and those who responded to initial treatment. The success rates of primary treatment were 80% with antibiotics alone, 90% with aspiration, and 96% with I&D (P = 0.35). The median time to follow-up survey was 6.5 y [IQR 4.4, 8.5]. Four patients who underwent I&D initially reported significant scarring. CONCLUSIONS: Treatment modality was not associated with persistent disease. A trial of antibiotics alone may be considered to minimize the risk of breast bud damage and adverse cosmetic outcomes with invasive intervention.

Mycoplasma bovis subverts autophagy to promote intracellular replication in bovine mammary epithelial cells cultured in vitro.

Mycoplasma species are the smallest prokaryotes capable of self-replication. To investigate Mycoplasma induced autophagy in mammalian cells, Mycoplasma bovis (M. bovis) and bovine mammary epithelial cells (bMEC) were used in an in vitro infection model. Initially, intracellular M. bovis was enclosed within a membrane-like structure in bMEC, as viewed with transmission electron microscopy. In infected bMEC, increased LC3II was verified by Western blotting, RT-PCR and laser confocal microscopy, confirming autophagy at 1, 3 and 6 h post-infection (hpi), with a peak at 6 hpi. However, the M. bovis-induced autophagy flux was subsequently blocked. P62 degradation in infected bMEC was inhibited at 3, 6, 12 and 24 hpi, based on Western blotting and RT-PCR. Beclin1 expression decreased at 12 and 24 hpi. Furthermore, autophagosome maturation was subverted by M. bovis. Autophagosome acidification was inhibited by M. bovis infection, based on detection of mCherry-GFP-LC3 labeled autophagosomes; the decreases in protein levels of Lamp-2a indicate that the lysosomes were impaired by infection. In contrast, activation of autophagy (with rapamycin or HBSS) overcame the M. bovis-induced blockade in phagosome maturation by increasing delivery of M. bovis to the lysosome, with a concurrent decrease in intracellular M. bovis replication. In conclusion, although M. bovis infection induced autophagy in bMEC, the autophagy flux was subsequently impaired by inhibiting autophagosome maturation. Therefore, we conclude that M. bovis subverted autophagy to promote its intracellular replication in bMEC. These findings are the impetus for future studies to further characterize interactions between M. bovis and mammalian host cells.

LsrR, the effector of AI-2 quorum sensing, is vital for the H2O2 stress response in mammary pathogenic Escherichia coli.

Mammary pathogenic Escherichia coli (MPEC) is an important causative agent of mastitis in dairy cows that results in reduced milk quality and production, and is responsible for severe economic losses in the dairy industry worldwide. Oxidative stress, as an imbalance between reactive oxygen species (ROS) and antioxidants, is a stress factor that is common in most bacterial habitats. The presence of ROS can damage cellular sites, including iron-sulfur clusters, cysteine and methionine protein residues, and DNA, and may cause bacterial cell death. Previous studies have reported that Autoinducer 2 (AI-2) can regulate E. coli antibiotic resistance and pathogenicity by mediating the intracellular receptor protein LsrR. This study explored the regulatory mechanism of LsrR on the H2O2 stress response in MPEC, showing that the transcript levels of lsrR significantly decreased under H2O2 stress conditions. The survival cell count of lsrR mutant XW10/pSTV28 was increased about 3080-fold when compared with that of the wild-type WT/pSTV28 in the presence of H2O2 and overexpression of lsrR (XW10/pUClsrR) resulted in a decrease in bacterial survival rates under these conditions. The ß-galactosidase reporter assays showed that mutation of lsrR led to a remarkable increase in expression of the promoters of ahpCF, katG and oxyR, while lsrR-overexpressing significantly reduced the expression of ahpCF and katG. The electrophoretic mobility shift assays confirmed that LsrR could directly bind to the promoter regions of ahpCF and katG. These results revealed the important role played by LsrR in the oxidative stress response of MPEC.

Bacteriology of pediatric breast abscesses beyond the neonatal period.

BACKGROUND: Limited data exist regarding the presentation and bacteriology of nonneonatal pediatric breast abscess. OBJECTIVE: To determine the bacteriology and characteristic presentation of pediatric breast abscesses in a tertiary care center. METHODS: Cross-sectional study of patients age 1 month to 21 years admitted to a pediatric Emergency Department (ED) between 1996 and 2018 with a breast abscess. Patients with pre-existing conditions were excluded. Records were reviewed to determine demographics, history, physical exam findings, wound culture results, imaging and ED disposition. We used descriptive statistics to describe prevalence of different bacteria. RESULTS: We identified 210 patients who met study criteria. Median age was 13.6 years [IQR 6.6, 17.4], and 91% (191/210) were females. Ninety-two patients (43.8%) were 'pre-treated' with antibiotics prior to ED visit, and 33/210 (16%) were febrile. Ultrasound was obtained in 85 patients (40.5%), 69 patients had a single abscess and 16 had multiple abscesses. Most patients were treated with antibiotics and 100 had a surgical intervention, of these 89 had I&D and 11 a needle aspiration. Admission rate was 45%. Culture results were available for 75 (75%). Thirty-three (44%) had a negative culture, or grew non-aureus staphylococci or other skin flora. Culture were positive for MSSA 21 (28%), MRSA 13 (17%), Proteus mirabilis 2 (2.6%), Serratia 1 (1.3%). Other organisms include Gram-negative bacilli, group A Streptococcus and enterococcus. CONCLUSIONS: Non-neonatal pediatric breast abscess bacteriology is no different than data published on other skin abscesses. MRSA coverage should be considered based on local prevalence in skin infections.

Differences in virulence between the two more prevalent Staphylococcus aureus clonal complexes in rabbitries (CC121 and CC96) using an experimental model of mammary gland infection.

Staphylococcal mastitis is a major health problem in humans and livestock that leads to economic loss running in millions. This process is currently one of the main reasons for culling adult rabbit does. Surprisingly, the two most prevalent S. aureus lineages isolated from non-differentiable natural clinical mastitis in rabbits (ST121 and ST96) generate different immune responses. This study aimed to genetically compare both types of strains to search for possible dissimilarities to explain differences in immune response, and to check whether they showed similar virulence in in vitro tests as in experimental intramammary in vivo infection. The main differences were observed in the enterotoxin gene cluster (egc) and the immune-evasion-cluster (IEC) genes. While isolate ST121 harboured all six egc cluster members (seg, sei, selm, seln, selo, selu), isolate ST96 lacked the egc cluster. Strain ST96 carried a phage integrase Sa3 (Sa3int), compatible with a phage integrated into the hlb gene (ß-haemolysin-converting bacteriophages) with IEC type F, while isolate ST121 lacked IEC genes and the hlb gene was intact. Moreover, the in vitro tests confirmed a different virulence capacity between strains as ST121 showed greater cytotoxicity for erythrocytes, polymorphonuclear leukocytes and macrophages than strain ST96. Differences were also found 7 days after experimental intramammary infection with 100 colony-forming units. The animals inoculated with strain ST121 developed more severe gross and histological mastitis, higher counts of macrophages in tissue and of all the cell populations in peripheral blood, and a significantly larger total number of bacteria than those infected by strain ST96.

Fecal non-aureus Staphylococci are a potential cause of bovine intramammary infection.

The presence of non-aureus staphylococci (NAS) in bovine rectal feces has recently been described. Similar to other mastitis causing pathogens, shedding of NAS in the environment could result in intramammary infection. The objective of this study was to investigate whether NAS strains present in feces can cause intramammary infection, likely via teat apex colonization. During a cross-sectional study in 5 dairy herds, samples were collected from the habitats quarter milk, teat apices, and rectal feces from 25%, 10%, and 25% of the lactating cows, respectively, with a cow serving as the source of one type of sample only. Samples from clinical mastitis cases were continuously collected during the 1-year study period as well. The 6 most prevalent NAS species, Staphylococcus (S.) chromogenes, S. cohnii, S. devriesei, S. equorum, S. haemolyticus, and S. hominis, were further subtyped by random amplification of polymorphic deoxyribonucleic acid polymerase chain reaction (RAPD-PCR), when the same NAS species was present in the same herd in the three habitats. For S. chromogenes, S. cohnii, S. devriesei, and S. haemolyticus, the same RAPD type was found in rectal feces, teat apices, and quarter milk, indicating that fecal NAS can infect the mammary gland. For S. hominis and S. equorum, we were unable to confirm the presence of the same RAPD types in the three habitats.

Imaging and clinical features of breast tuberculosis: a review series of 62 cases.

AIM: To outline the disease burden of breast tuberculosis (TB) as a quantitative analysis amongst three tertiary hospitals in South Africa, with correlation to their clinical, demographic, and imaging features. MATERIALS AND METHODS: A retrospective analysis was undertaken over an 18-month period (01/01/2017-30/06/2018) of all patients undergoing laboratory investigations for breast disease at the mammography departments of these three tertiary centres. RESULTS: The prevalence of breast TB was 2.5% (n=62) of 2,516 patients. The median age of presentation was 38.5 years (interquartile range [IQR] 33-45). HIV status was known in 45 patients, of whom 36 were HIV infected (80%, 95% CI: 0.65-0.90, p<0.0001). Based on the ultrasound and/or mammogram findings, the patients were classified into five categories: TB breast abscess (40.3%), inflammatory/disseminated (24.2%), isolated TB lymphadenitis (22.6%), nodular (11.3%), and sclerosing form (1.6%). Histology demonstrated necrotising granulomatous inflammation in 57 cases (92%). Acid-fast bacilli (AFB) were positive in 8.1% (n=5) of the cytology and 16.1% (n=10) of the histology specimens. Culture for Mycobacterium tuberculosis was positive in 27% (17 cases), and in 12.9% (n=8). AFB were detected histologically using polymerase chain reaction (PCR) testing. CONCLUSION: Knowledge of the varied clinical and radiological features is necessary to maintain a high degree of suspicion to prevent misdiagnoses, inappropriate management, and complications. Ultrasound-guided core biopsy rather than fine-needle aspiration (FNA) is advocated as the first-line intervention in diagnosing or excluding this disease, as it yields a better tissue sample and more often a positive diagnosis.

The microbiome and breast cancer: a review.

The human microbiome plays an integral role in physiology, with most microbes considered benign or beneficial. However, some microbes are known to be detrimental to human health, including organisms linked to cancers and other diseases characterized by aberrant inflammation. Dysbiosis, a state of microbial imbalance with harmful bacteria species outcompeting benign bacteria, can lead to maladies including cancer. The microbial composition varies across body sites, with the gut, urogenital, and skin microbiomes particularly well characterized. However, the microbiome associated with normal breast tissue and breast diseases is poorly understood. Collectively, studies have shown that breast tissue has a distinct microbiome with particular species enriched in the breast tissue itself, as well as the nipple aspirate and gut bacteria of women with breast cancer. More importantly, the breast and associated microbiomes may modulate therapeutic response and serve as potential biomarkers for diagnosing and staging breast cancer.

Outbreak report of investigation and control of an outbreak of Panton-Valentine Leukocidin-positive methicillin-sensitive Staphylococcus aureus (PVL-MSSA) infection in neonates and mothers.

BACKGROUND: In January 2011, there was an outbreak of Panton-Valentine Leukocidin-positive methicillin-sensitive Staphylococcus aureus (PVL-MSSA) infection in a neonatal unit (NNU). We describe the investigation and control of an outbreak of PVL-MSSA infection in neonates. SETTING: Neonatal unit in West London. METHODS: We performed descriptive and analytical (case-control study) epidemiological investigations. Microbiological investigations including screening of MSSA isolates by PCR for the presence of the luk-PV, mecA and mecC genes and comparison of isolate with Pulsed field gel electrophoresis (PFGE). Control measures were also introduced. RESULTS: Sixteen babies were infected/colonised with the outbreak strain. Of these, one baby developed blood stream infection, 12 developed skin pustules and four babies were colonised. Four mothers developed breast abscesses. Eighty-seven babies in the unit were screened and 16 were found to have same PVL-MSSA strain (spa type t005, belonging to MLST clonal complex 22). Multivariate analysis showed gestational age was significantly lower in cases compared to controls (mean gestational age: 31.7 weeks v 35.6 weeks; P = 0.006). Length of stay was significantly greater for cases, with a median of 25 days, compared to only 6 days for controls (P = 0.01). Most (88%) cases were born through caesarean section, compared to less than half of controls. (P = 0.002). No healthcare worker carriers and environmental source was identified. The outbreak was controlled by stopping new admissions to unit and reinforcing infection control precautions. The outbreak lasted for seven weeks. No further cases were reported in the following year. CONCLUSIONS: Infection control teams have to be vigilant for rising prevalence of particular S. aureus clones in their local community as they may cause outbreaks in vulnerable populations in healthcare settings such as NNUs.

Fulminant gas-forming breast abscess associated with synergistic Veillonella infection.

We present a rare case of a rapidly fulminant and destructive breast abscess with gas production by the synergistic infection of Veillonella and Streptococcus species. To our knowledge, this is the first reported case of Veillonella infection in the breast. Early recognition, empiric antibiotic cover, aggressive surgical debridement, and drainage are necessary to avoid systemic septicemia. Staged reconstructive breast surgery allows for correction any resultant breast deformity.

Post-traumatic necrotising fasciitis of the breast: a case study with literature review.

Necrotising fasciitis is a rare infection of the skin and underlying soft tissue. It primarily involves the extremities and rarely the breast. Primary necrotising fasciitis of the breast in a non-lactating, healthy female is rarer still. The authors present the case report of a patient presenting with primary necrotising fasciitis of the breast after sustaining a penetrating injury. The patient was managed successfully with serial debridement and negative pressure wound therapy (NPWT). To our knowledge only 19 such cases have been reported in the indexed literature so far. This is also the eighth case globally of primary necrotising fasciitis of the breast in a non-lactating female without any associated immunosuppression, which is the basis of reporting this case.

Validation of the American Association for the Surgery of Trauma's emergency general surgery breast infection grading system.

BACKGROUND: The American Association for the Surgery of Trauma (AAST) developed emergency general surgery (EGS) grading systems for multiple diseases to standardize classification of disease severity. The grading system for breast infections has not been validated. We aimed to validate the AAST breast infection grading system. METHODS: Multi-institutional retrospective review of all adult patients with a breast infection diagnosis at Mayo Clinic Rochester 1/2015-10/2015 and Pietermaritzburg South African Hospital 1/2010-4/2016 was performed. AAST EGS grades were assigned by two independent reviewers. Inter-rater reliability was measured using the agreement statistic (kappa). Final AAST grade was correlated with patient and treatment factors using Pearson's correlation coefficient. RESULTS: Two hundred twenty-five patients were identified: grade I (n = 152, 67.6%), II (n = 44, 19.6%), III (n = 25, 11.1%), IV (n = 0, 0.0%), and V (n = 4, 1.8%). At Mayo Clinic Rochester, AAST grades ranged from I-III. The kappa was 1.0, demonstrating 100% agreement between reviewers. Within the South African patients, grades included II, III, and V, with a kappa of 0.34, due to issues of the grading system application to this patient population. Treatment received correlated with AAST grade; less severe breast infections (grade I-II) received more oral antibiotics (correlation [-0.23, P = 0.0004]), however, higher AAST grades (III) received more intravenous antibiotics (correlation 0.29, P <0.0001). CONCLUSIONS: The AAST EGS breast infection grading system demonstrates reliability and ease for disease classification, and correlates with required treatment, in patients presenting with low-to-moderate severity infections at an academic medical center; however, it needs further refinement before being applicable to patients with more severe disease presenting for treatment in low-/middle-income countries.

Predictors of outcomes in managing breast abscesses-A large retrospective single-center analysis.

We have retrospectively examined a wide range of clinical characteristics, sonographic features, microbiology, and antibiotic regimens in patients with breast abscesses to seek predictive features related to outcome. Because consensus for optimal treatment of breast abscesses has moved toward minimally invasive management using single or repeated needle aspiration (ASP) coupled with adjuvant antibiotics, we assessed whether any factors correlate with the need for repeat procedures by analyzing the number of ASPs and/or surgical incision and drainage (I&D) per abscess. We examined 127 abscesses in 114 patients from a single urban public hospital, and among clinical characteristics, we found that only smoking history (P = .021) and the presence of nipple rings (P = .005) were associated with greater likelihood of necessitating repeat for abscess resolution procedures. Neither diabetes, lactational status, and HIV nor ultrasound features imaging of an abscess including size >3 cm, multiloculation, rind thickness, or central vs peripheral location were correlated with the need for a repeat procedure. Likewise, no specific micro-organisms predicted a greater likelihood of requiring repeat procedures, and no specific initial antibiotic regimen (gram-positive and/or gram-negative or multiresistance coverage) impacted clinical outcomes. Our data indicate that no specific imaging abscess characteristics, type of micro-organism, or initial choice of antibiotics affect outcomes, and therefore, these features should not preclude attempts at conventional therapy by repeated aspiration and antibiotic treatment. While a smoking history and presence of a nipple ring may increase the risk of a prolonged course, the decision to change antibiotics or repeat aspiration should rely instead on clinical evaluation and judgment by experienced physicians.

In vitro antibiotic susceptibility and biofilm production of Staphylococcus aureus isolates recovered from bovine intramammary infections that persisted or not following extended therapies with cephapirin, pirlimycin or ceftiofur.

Staphylococcus aureus intramammary infections (IMIs) have low cure rates using standard antibiotic treatment and increasing the duration of treatment usually improves therapeutic success. Chronic IMIs are thought to be caused by bacteria presenting a specific virulence phenotype that includes the capacity to produce greater amounts of biofilm. In this study, antibiotic susceptibility and biofilm production by S. aureus isolates recovered from IMIs that were cured or not following an extended therapy with cephapirin, pirlimycin or ceftiofur for 5, 8 and 8 days, respectively, were compared. An isolate was confirmed as from a persistent case (not cured) if the same S. aureus strain was isolated before and after treatment as revealed by the same VNTR profile (variable number of tandem repeats detected by multiplex PCR). The antibiotic minimal inhibitory concentrations (MICs) were determined for these isolates as well as the capacity of the isolates to produce biofilm. Isolates from persistent cases after extended therapy with cephapirin or ceftiofur had higher MICs for these drugs compared to isolates from non-persistent cases (p < 0.05) even though the antibiotic susceptibility breakpoints were not exceeded. Isolates of the ceftiofur study significantly increased their biofilm production in presence of a sub-MIC of ceftiofur (p < 0.05), whereas isolates from the pirlimycin group produced significantly less biofilm in presence of a sub-MIC of pirlimycin (p < 0.001). Relative antibiotic susceptibility of the isolates as well as biofilm production may play a role in the failure of extended therapies. On the other hand, some antibiotics may counteract biofilm formation and improve cure rates.

Breast abscess due to Finegoldia magna in a non-puerperal women.

Finegoldia magna is a Gram-positive anaerobic coccus involved in a wide variety of infections. We report a unusual case of breast abscess in a non-puerperal patient. A 46-year-old woman presented with pain and a nodular lesion in the left breast. Culture of abscess drainage resulted in isolation of F. magna. Initial treatment with clindamycin was changed to a definitive treatment with amoxicillin-clavulanate for 10 days due to resistance to clindamycin, and improvement of this infection was documented.

Drop the Knife and Pick Up the Transducer.

Ultrasound has a diagnostic and procedural role when managing breast abscesses. We present the case of an adolescent girl diagnosed with a breast abscess with point-of-care ultrasound who subsequently underwent ultrasound-guided aspiration as a form of definitive management.

Mammary candidiasis: molecular-based detection of Candida species in human milk samples.

In this prospective and monocentric study, we investigated the performance of a commercialized real-time polymerase chain reaction (RT-PCR) test system for the specific detection of DNA from Candida albicans, C. dubliniensis, C. glabrata, C. krusei, C. lusitaniae, C. parapsilosis, and C. tropicalis in human milk samples of patients suspicious of mammary candidiasis. For this purpose, 43 breast-feeding women with characteristic symptoms of mammary candidiasis and 40 asymptomatic controls were enrolled. By culture, Candida spp. were detected in 8.8 % (4/46) and 9.3 % (4/43) of patient and control samples, respectively. Candida albicans (2/46), C. parapsilosis (1/46), and C. guilliermondii (1/46) were present in patient samples, and C. lusitaniae (3/43) and C. guilliermondii (1/43) were present in the controls. After RT-PCR was applied, Candida spp. were found to be present in 67.4 % (31/46) and 79.1 % (34/43) of patient and control samples investigated, respectively. PCR detection of C. albicans and C. parapsilosis revealed only a low sensitivity and specificity of 67.4 % and 41.9 %, respectively. Our data do not support the use of Candida RT-PCR for sensitive and specific diagnosis of mammary candidiasis.

Breast abscess due to Salmonella Typhimurium in a patient with rheumatoid arthritis: a case report.

BACKGROUND: This is the first report of breast abscess due to Salmonella enterica serotype Typhimurium. Staphylococcus aureus is known as the most common cause of breast abscess. Salmonella spp. may occasionally form localized abscesses after dissemination to various organ systems following a bacteraemia. But breast abscess related to Salmonella spp is a very rare complication. CASE PRESENTATION: A 43-year-old female patient referred to our hospital with a lump, fever and mild pain in her breast. The patient was not pregnant or lactating at that time. She had a history of rheumatoid arthritis for 5 years and was under immunosuppressive therapy. Ultrasonography of the breast revealed an abscess. The abscess was drained and sent for culture to medical microbiology laboratory. The microorganism was identified as Salmonella enterica serotype Typhimurium and found to be sensitive to all antibiotics tested. The patient was cured after surgical debridement and antibiotic therapy. The abscess did not recur again. CONCLUSIONS: This case is presented to draw attention to non-typhoidal Salmonella as rare causes of breast abscess and submission of specimens to the microbiology laboratory for accurate diagnosis and treatment especially in patients with underlying immunosuppressive diseases.