Species designation of streptococci causing infective endocarditis in patients with mitral valve prolapse.

OBJECTIVES: Viridans group streptococci (VGS) have been previously linked to infective endocarditis (IE) in patients with mitral valve prolapse (MVP). The species identification of VGS is now available in clinical laboratories; however, it has not been examined in MVP IE. Therefore, we detailed the clinical profile, species designations, and antibiotic susceptibility of VGS isolates from patients with MVP IE. METHODS: We retrospectively queried all adults with MVP and a definite or possible IE diagnosis seen at medical centers of the Mayo Clinic Enterprise from January 2009 to December 2021. Data, including clinical characteristics, comorbidities, microbiology, and outcomes, were extracted from electronic health records. VGS isolates from patients with MVP and IE were subclassified into mutans, salivarius, anginosus, sanguinis, and mitis groups. RESULTS: A total of 38 patients with MVP with IE due to streptococcal species were included. Overall, median age was 62.4 years and 32% of patients were females. The most prevalent comorbidities were diabetes mellitus (26%), hypertension (21%), heart failure (16%), and malignancy (16%). A total of (37%) patients presented with an embolic event at the time of their IE diagnosis, 27 (66%) required valve surgery, and no patient died within the hospital stay. The Streptococcus mitis group was the predominant (n = 17, 45%) species designation; S. anginosus and S. sanguinis were identified in three (8%) each; S. mutans in two (5%); and S. salivarius in one (3%). Non-VGS streptococcal pathogens included S. agalactiae in three patients (8%), S. equi in two (5%), and S. dysgalactiae and S. bovis in one each (3%). VGS were identified in five (13%) patients, but species designation was not done. No penicillin resistance was identified among the isolates. CONCLUSION: The S. mitis group was the predominant species in our investigation. Continued evaluation of VGS species should be considered to profile the IE risk based on species identification.

Persistent Bacillus cereus Bacteremia in an Immunocompetent Patient With a History of Polysubstance Abuse.

Extraintestinal infections are rare with Bacillus cereus and include endocarditis, pneumonia, and meningoencephalitis. It has been primarily reported in immunosuppressed individuals with hematological malignancies and rarely in people who inject drugs (PWIDs). Herein, we report the case of a healthy adult woman with no underlying conditions except for injection drug use who presented with signs of meningitis. A 40-year-old female intravenous (IV) drug addict presented to the hospital with a chief complaint of severe headache. She had a fever of 38 °C, and her neurological examination was unremarkable. Laboratory results were significant for a white blood cell (WBC) count of 20.0 × 109/L (reference range: 4.5 to 11.0 × 109/L) and urine toxicology that was positive for amphetamines and cocaine. A lumbar puncture showed a total of 1,736 nucleated cells/µL, 88% neutrophils, a glucose level of 73 mg/dL, and a significantly elevated protein level of 155 mg/dL. B. cereus grew in blood cultures and cerebrospinal fluid (CSF) cultures. Once the growth of B. cereus was identified in the CSF, intravenous vancomycin was started. After leaving against medical advice (AMA), the patient presented again to the hospital, and a lumbar puncture was repeated. Cerebrospinal fluid showed total nucleated cells of 13 cells/µL, but the patient remained bacteremic. An echocardiogram, computerized tomography (CT) of the abdomen and pelvis, and tagged white blood cell scan could not identify a source for the bacteremia. Despite receiving two weeks of IV vancomycin, her blood cultures remained consistently positive for B. cereus without identifying a clear source of infection. Although B. cereus rarely affects the central nervous system, there have been a few cases where immunosuppression has been linked to the infection. We report an unusual case of a patient who continued to be bacteremic despite a thorough search for a source of B. cereus infection and IV vancomycin treatment. As a result, we raise the possibility of addictive behavior due to the patient's pattern of leaving the hospital against medical advice and returning with recurrent bacteremia. A thorough history and careful search for a source of infection are required when B. cereus grows persistently in blood cultures.

Staphylococcus aureus bacteraemia and mortality: a population-based study in Olmsted County, Minnesota, from 2006 to 2020.

OBJECTIVES: To provide an evaluation of predictors of 6-month mortality in incident Staphylococcus aureus bacteraemia cases. METHODS: A retrospective population-based study of 541 adult residents of Olmsted County, MN with monomicrobial S. aureus bacteraemia from 1 January 2006 through 31 December 2020. Multivariable Cox regression was used to investigate risk factors of 6-month mortality. RESULTS: The median (interquartile range [IQR]) age of 541 patients with S. aureus bacteraemia was 66.8 (54.4-78.5) years and 39.6% were female. The median (IQR) Charlson Comorbidity Index was 6 (3-9). Overall, 144 patients died during the six-month period following their initial episode (30-day and 6-month mortality = 16.5% and 26.7%, respectively). In a multivariable analysis, older age, ICU admission, and unknown source of infection were significant predictors of increased 6-month mortality. In contrast, having an infectious diseases (ID) consultation was associated with reduced mortality in the first 2 weeks of follow-up. Secondary analyses revealed an early benefit of ID consultation during the first 30 days of follow-up and that infective endocarditis was an additional predictor of 6-month mortality. CONCLUSIONS: To our knowledge, this investigation represents the only US population-based study evaluating predictors of mortality in patients with S. aureus bacteraemia. The finding of a short-term survival benefit associated with early ID consultation may be due to more extensive diagnostic efforts.

A Population-Based Evaluation of Polymicrobial Staphylococcus aureus Bacteremia.

OBJECTIVE: To provide an evaluation of incidence and six-month mortality rates of polymicrobial Staphylococcus aureus bacteremia (p-SAB) in the United States (US). METHODS: A retrospective population-based study of all incident adults with monomicrobial SAB (m-SAB) and p-SAB in Olmsted County, Minnesota (MN) from 1 January 2006, through 31 December 2020, was conducted. Demographics, clinical characteristics, in-hospital outcomes, and six-month survival were compared between groups. RESULTS: Overall, 31 incident p-SAB cases occurred during the 15-year study period, corresponding to an overall age- and sex-standardized incidence rate of 1.9/100,000 person-years (95% CI, 1.3-2.6). One-third of p-SAB cases were due to MRSA, and almost one-half (15/31) were caused by Gram-positive bacteria. As compared to the 541 cases with incident m-SAB, p-SAB patients were more likely to have a catheter-related infection (p = 0.008) and less likely to be community-acquired cases (p = 0.027). The unadjusted risk of six-month mortality was greater in the p-SAB group (14/31, 45.2%) compared to the m-SAB group (144/541, 26.6%) (HR = 1.94, 95% CI = 1.12-3.36, p = 0.018). After adjusting for relevant covariates, this difference approached significance (HR = 1.93, 95% = CI 0.96-3.87, p = 0.064). CONCLUSIONS: To our knowledge, the current investigation represents the only US population-based study evaluating p-SAB patients. We found lower incidence rates for p-SAB than previously reported, with almost one-half of the cases caused by Gram-positive bacteria. Furthermore, these patients had poor survival compared to incident m-SAB cases.

Antimicrobial Treatment of Pseudomonas aeruginosa Severe Sepsis.

Pseudomonas aeruginosa is a pathogen often encountered in a healthcare setting. It has consistently ranked among the most frequent pathogens seen in nosocomial infections, particularly bloodstream and respiratory tract infections. Aside from having intrinsic resistance to many antibiotics, it rapidly acquires resistance to novel agents. Given the high mortality of pseudomonal infections generally, and pseudomonal sepsis particularly, and with the rise of resistant strains, treatment can be very challenging for the clinician. In this paper, we will review the latest evidence for the optimal treatment of P. aeruginosa sepsis caused by susceptible as well as multidrug-resistant strains including the difficult to treat pathogens. We will also discuss the mode of drug infusion, indications for combination therapy, along with the proper dosing and duration of treatment for various conditions with a brief discussion of the use of non-antimicrobial agents.

Mycobacterium ulcerans lung infection in an immunocompetent patient.

Mycobacterium ulcerans has been implicated in cutaneous manifestations in humans, causing persistent wounds called Buruli ulcer. However, it has not been associated with pulmonary infections in humans to date. Herein, we report a case of an immunocompetent adult man with no underlying medical problems presenting with dyspnoea and generalised malaise and diagnosed with M. ulcerans lung infection. The patient was prescribed clarithromycin 500 mg two times per day, rifampin 300 mg two tablets daily and moxifloxacin 400 mg daily for 6 months, with complete resolution of his symptoms.

Incidence of Monomicrobial Staphylococcus aureus Bacteremia: A Population-Based Study in Olmsted County, Minnesota-2006 to 2020.

Background: Population-based studies of Staphylococcus aureus bacteremia (SAB) in the United States are limited. We provide a contemporary evaluation of SAB incidence in Olmsted County, Minnesota, from 2006 to 2020. Methods: This was a retrospective population-based study of all adult patients with SAB residing in Olmsted County from 1 January 2006 through 31 December 2020. Initial episodes of SAB were identified using the microbiology laboratory databases at both Olmsted Medical Center and Mayo Clinic Rochester. Results: Overall, 541 incident SAB cases were identified with a median age of 66.8 (interquartile range, 54.4-78.5) years, and 60.4% were male. Among these cases, 298 (56.2%) were due to methicillin-susceptible S aureus (MSSA) and 232 (43.8%) cases of methicillin-resistant S aureus (MRSA). The overall age- and sex-adjusted SAB incidence rate (IR) was 33.9 (95% confidence interval [CI], 31.0-36.8) cases/100 000 person-years (PY). Males had a higher age-adjusted IR of 46.0 (95% CI, 41.0-51.0) cases/100 000 PY compared to females (IR, 24.4 [95% CI, 21.1-27.7] cases/100 000 PY). Age- and sex-adjusted SAB IRs due to MSSA and MRSA were 18.7 and 14.6 cases/100 000 PY, respectively, and the percentage of incident SAB cases due to MRSA fluctuated across the study period. There was no apparent temporal trend in SAB incidence over the study period (P = .093). Conclusions: Our investigation represents the only contemporary population-based study in the United States. Despite the impression that SAB incidence may have increased based on Centers for Disease Control and Prevention surveillance data, our finding of no change in SAB incidence was somewhat unanticipated.

Incidence Trends and Epidemiology of Staphylococcus aureus Bacteremia: A Systematic Review of Population-Based Studies.

OBJECTIVES: To determine incidence trends of Staphylococcus aureus bacteremia (SAB) from population-based studies from multiple countries. METHODS: A contemporary systematic review was conducted using Ovid Cochrane Central Register of Controlled Trials (1991+), Ovid Embase (1974+), Ovid Medical Literature Analysis and Retrieval System Online (MEDLINE) (1946+ including epub ahead of print, in-process & other non-indexed citations), and Web of Science Core Collection (Science Citation Index Expanded 1975+ and Emerging Sources Citation Index 2015+). Two authors (J.R.H. and J.A.Q.M.) independently reviewed all studies and included those that reported population-based incidence of SAB in patients aged 18 years and older. RESULTS: Twenty-six studies met inclusion criteria with the highest number (n=6) of studies conducted in Canada. The incidence of SAB ranged from 9.3 to 65 cases/100,000/year. The median age of patients with SAB ranged from 62 to 72 years and SAB cases were more commonly observed in men than in women. The most common infection sources were intravascular catheters and skin and soft tissue infections. SAB incidence trends demonstrated high variability for geographic regions and calendar years. Overall, there was no change in the incidence trend across all studies during the past two decades. CONCLUSION: Multiple factors, both pros, and cons are likely responsible for the overall stable SAB incidence in countries included in this systematic review. Some of these factors vary in geographic location and prompt additional investigations from countries not included in the current review so that a more global characterization is defined.

Burkholderia cepacia Infections at Sites Other than the Respiratory Tract: A Large Case Series from a Tertiary Referral Hospital in Lebanon.

OBJECTIVES: The Burkholderia cepacia complex (Bcc), which was originally thought to be a single species, represents a group of 24 distinct species that are often resistant to multiple antibiotics, and usually known to cause life-threatening pulmonary infections in cystic fibrosis patients. Herein we describe a series of non-respiratory Bcc infections, the risk factors and epidemiologic factors, in addition to the clinical course. PATIENTS AND METHODS: This is a retrospective chart review of 44 patients with documented B. cepacia infections isolated from sites other than the respiratory tract admitted between June 2005 and February 2020 to the American University of Beirut Medical Center (AUBMC), a tertiary referral hospital for Lebanon and the Middle East region. The epidemiological background of these patients, their underlying risk factors, the used antibiotic regimens, and the sensitivities of the B. cepacia specimens were collected. RESULTS: The majority of the Bcc infections (26/44, 59.1%) were hospital-acquired infections. The most common nationality of the patients was Iraqi (18/44, 40.9%), and the most common site of infection was bacteremia (17/44, 38.6%), followed by skin and soft tissues infections (16/44, 36.4%) and vertebral osteomyelitis (8/44, 18.2%). Most of the isolated B. cepacia were susceptible to ceftazidime, carbapenems, followed by TMP-SMX. Patients responded well to therapy with good overall outcome. CONCLUSIONS: Bcc can cause infections outside the respiratory tract, mostly as hospital-acquired infections and in immunocompromised patients. Most patients were referred from countries inflicted by wars raising the possibility of a potential role of conflicts which need to be investigated in future studies. Directed therapy according to susceptibility results proved effective in most patients.

Contemporary demographics, diagnostics and outcomes in non-bacterial thrombotic endocarditis.

OBJECTIVE: Non-bacterial thrombotic endocarditis (NBTE) is a syndrome characterised by cardiac valve vegetations and/or thickening due to non-infective mechanisms. Nowadays, a premortem diagnosis of NBTE is possible based on echocardiographic findings. Therefore, to better characterise this disease, we performed a contemporary review of the epidemiology, demographics, diagnosis and clinical outcomes of these patients. METHODS: Adults with a diagnosis of NBTE seen within the Mayo Clinic Enterprise from December 2014 to December 2021 were included. NBTE diagnosis was identified by clinicians representing at least two specialties including cardiology, infectious diseases, rheumatology and oncology. Patients with positive blood cultures, infective endocarditis, culture-negative endocarditis and denial of research authorisation were excluded. All patients had a 1-year follow-up. RESULTS: Forty-eight cases were identified; mean age was 60.0±13.8 years, 75% were female. The most prevalent comorbidities were malignancy (52.1%) and connective tissue disease (37.5%). Valvular abnormalities included 41 (85.4%) patients with vegetations, 43 (89.6%) patients with thickening and 26 (54.2%) with moderate to severe regurgitation. Thirty-eight (79.2%) patients had an embolic event (stroke in 26 (54.2%) patients) within 1 month of NBTE diagnosis and 16 (33.3%) patients died within 1 year of NBTE diagnosis. Metastatic tumours and lung cancer were associated with 1-year all-cause mortality (p=0.0017 and p=0.0004, respectively). CONCLUSIONS: NBTE was more prevalent in females and embolic complications were the most frequent clinical finding. Overall, patients with NBTE had a poor prognosis, particularly in those with lung cancer or metastatic tumours. Further studies in patients with NBTE are needed given its morbidity and mortality.

A clinical profile of infective endocarditis in patients with recent COVID-19: A systematic review.

BACKGROUND: Coronavirus disease 2019 (COVID-19) can progress to cardiovascular complications which are linked to higher in-hospital mortality rates. Infective endocarditis (IE) can develop in patients with recent COVID-19 infections, however, characterization of IE following COVID-19 infection has been lacking. To better characterize this disease, we performed a systematic review with descriptive analysis of the clinical features and outcomes of these patients. METHODS: Our search was conducted in 8 databases for all published reports of probable or definite IE in patients with a prior COVID-19 confirmed diagnosis. After ensuring an appropriate inclusion of the articles, we extracted data related to clinical characteristics, modified duke criteria, microbiology, outcomes, and procedures. RESULTS: Searches generated a total of 323 published reports, and 20 articles met our inclusion criteria. The mean age of patients was 52.2 ± 16.9 years and 76.2% were males. Staphylococcus aureus was isolated in 8 (38.1%) patients, Enterococcus faecalis in 3 patients (14.3%) and Streptococcus mitis/oralis in 2 (9.5%) patients. The mean time interval between COVID-19 and IE diagnoses was 16.7 ± 15 days. Six (28.6%) patients required critical care due to IE, 7 patients (33.3%) underwent IE-related cardiac surgery and 5 patients (23.8%) died during their IE hospitalization. CONCLUSIONS: Our systematic review provides a profile of clinical features and outcomes of patients with a prior COVID-19 infection diagnosis who subsequently developed IE. Due to the ongoing COVID-19 pandemic, it is essential that clinicians appreciate the possibility of IE as a unique complication of COVID-19 infection.

Diagnosis and Management of Invasive Candida Infections in Critically Ill Patients.

Invasive candidiasis (IC) has become a serious problem in the intensive care unit patients with an attributable mortality rate that can reach up to 51%. Multiple global surveillance studies have shown an increasing incidence of candidemia. Despite their limited sensitivity (21-71%), cultures remain the gold standard for the diagnosis of IC associated with candidemia. Many adjunct laboratory tests exist to support or rule out the diagnosis, each with its indications and limitations, including procalcitonin, 1,3-ß-D-glucan, mannan and anti-mannan antibodies, and Candida albicans germ tube antibody. In addition, polymerase chain reaction-based methods could expedite species identification in positive blood cultures, helping in guiding early empirical antifungal therapy. The management of IC in critically ill patients can be classified into prophylactic, preemptive, empiric, and directed/targeted therapy of a documented infection. There is no consensus concerning the benefit of prophylactic therapy in critically ill patients. While early initiation of appropriate therapy in confirmed IC is an important determinant of survival, the selection of candidates and drug of choice for empirical systemic antifungal therapy is more controversial. The choice of antifungal agents is determined by many factors, including the host, the site of infection, the species of the isolated Candida, and its susceptibility profile. Echinocandins are considered initial first-line therapy agents. Due to the conflicting results of the various studies on the benefit of preemptive therapy for critically ill patients and the lack of robust evidence, the Infectious Diseases Society of America (IDSA) omitted this category from its updated guidelines and the European Society of Intensive Care Medicine (ESICM) and the Critically Ill Patients Study Group of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) do not recommend it.

A Case of Concomitant Plasmodium falciparum Malaria and Bacillus cereus Bacteremia in a Returning Traveler From Tanzania.

Malaria has been associated with bacterial co-infections, but the importance of bacterial co-infections in uncomplicated malaria is poorly described. We report a unique case of a 27-year-old female with concomitant Plasmodium falciparum and Bacillus cereus bacteremia who acquired those infections while traveling in Tanzania but became ill only after returning to the United States. Blood parasites screen revealed Plasmodium falciparum and blood cultures obtained at presentation showed Bacillus cereus. Even after completing treatment for malaria, she continued to have abdominal pain and watery diarrhea, which improved only after IV vancomycin. Bacillus cereus bacteremia cases are reported in travelers and immigrants returning from countries where malaria transmission occurs, mainly from sub-Saharan Africa but co-infection with Plasmodium falciparum and Bacillus cereus has not been described in the literature yet. In this case, malaria symptoms resolved after targeted treatment was initiated but persistent diarrhea improved only after appropriate therapy against Bacillus cereus. Persistent watery diarrhea and dehydration in patients with malaria should raise concerns about Bacillus cereus co-infection.

New drugs for methicillin-resistant Staphylococcus aureus skin and soft tissue infections.

PURPOSE OF REVIEW: Staphylococcus aureus is a pathogen incriminated in skin and soft tissue infections (SSTIs), with methicillin-resistant S. aureus (MRSA) becoming the predominant cause and representing a significant burden to the healthcare system. The last updated Infectious Diseases Society of America (IDSA) guidelines concerning MRSA infections and SSTIs management were published in 2011 and 2014, respectively. The UK updated guidelines for MRSA infection treatment were published in 2021. Older treatment options may be associated with toxicity and require frequent dosing. There is a paucity of recent reviews on the armamentarium of new agents for MRSA SSTIs treatment. RECENT FINDINGS: Since 2005, several new antibiotics received a fast-track approval by the Food and Drug Administration (FDA) for SSTI treatment. These drugs include delafloxacin, omadacycline, tedizolid, ceftaroline, dalbavancin, oritavancin and telavancin. In this manuscript, we will review the data that led to these new drugs approval and discuss their advantages and disadvantages in MRSA SSTIs management. SUMMARY: MRSA is a major cause of SSTIs. Several novel therapies covering MRSA were FDA-approved for SSTIs. However, the current IDSA guidelines for MRSA infection and SSTIs as well as the recently published UK guidelines on MRSA treatment only consider these drugs as alternative choices or do not mention them at all.

Challenges to Antimicrobial Stewardship in the Countries of the Arab League: Concerns of Worsening Resistance during the COVID-19 Pandemic and Proposed Solutions.

The COVID-19 pandemic is expected to worsen the global problem of antimicrobial resistance (AMR). There is a heightened interest in understanding this effect and to develop antimicrobial stewardship (AMS) interventions accordingly to curb this threat. Our paper aims to evaluate the potential magnitude of COVID-19 on AMR and AMS with a focus on the countries of the Arab league, given the social, political, and economic environments. We also evaluate obstacles in applying the rational use of antibiotics, monitoring resistance trends in the midst of the pandemic, and evaluating the impact of the economic crisis in some countries. We aim to raise awareness about the potential effects of antibiotic overuse during the pandemic and to propose practical approaches to tackle this issue.

Bacterial bloodstream infections and patterns of resistance in patients with haematological malignancies at a tertiary centre in Lebanon over 10 years.

OBJECTIVES: Bacterial bloodstream infections (BSIs) with resistant pathogens in patients with haematological malignancies are rising due to increased use of novel chemotherapeutic agents and prophylactic antibiotics. Our goal was to understand the epidemiology and resistance patterns of bacterial pathogens in patients with haematological malignancies to help tailor empirical antibiotics and to limit resistance. METHODS: This was a retrospective chart review looking at bacterial BSI episodes between 2007-2017 in patients previously diagnosed with haematological malignancy at a tertiary-care centre in Lebanon. RESULTS: Among 165 hospitalised patients with haematological malignancy and bacterial BSI over 10 years, Gram-negative bacteria (GNB) caused 65.0% of all episodes, with the most common pathogens being Escherichia coli (45.6%), 79.6% of which were ESBL-producers, Pseudomonas aeruginosa (7.5%) and Acinetobacter baumannii (4.0%). The majority of the organisms (61.0%) were multidrug-resistant (MDR), with ANC < 100 neutrophils/µL (OR = 0.12, 95% CI 0.03-0.54) identified as an independent marker for increased multidrug resistance. The risk factors associated with increased mortality included recent use of amikacin (p<0.001) and infections with organisms resistant to amikacin (p<0.001) or ciprofloxacin (p=0.04). Our results reflect a persistent pattern of Gram-negative predominance with E. coli remaining the most common isolated pathogen in bacterial BSIs in patients with haematological malignancies. The relative frequency of GNB to Gram-positive bacteria remains similar to our data from 2007. CONCLUSION: The persistent divergence between worldwide data and the results observed in our centre and the increasing rates of MDR pathogens emphasise the importance of tailoring empirical antimicrobial therapy according to the centre's epidemiology.

Epidemiology of Methicillin-Resistant Staphylococcus Aureus in Arab Countries of the Middle East and North African (MENA) Region.

Available data suggest a high burden of methicillin-resistant staphylococcus aureus (MRSA) in Arab countries of the Middle East and North Africa (MENA). To review the MRSA rates and molecular epidemiology in this region, we used PubMed search engine to identify relative articles published from January 2005 to December 2019. Great heterogeneity in reported rates was expectedly seen. Nasal MRSA colonization ranged from 2%-16% in Gulf Cooperation Council (GCC), 1-9% in the Levant, and 0.2%-9% in North African Arab states. Infective MRSA rates ranged from 9%-38% in GCC, 28%-67% in the Levant, and 28%-57% in North African states. Studies demonstrated a wide clonal diversity in the MENA. The most common molecular types belonged to 5 clonal complexes (CC) known to spread worldwide: CC5, CC8, CC22, CC30, and CC80. The most prevalent strains had genotypes related to the European community-acquired MRSA (CA-MRSA), Brazilian/Hungarian hospital-acquired MRSA (HA-MRSA), UK-EMRSA-15 HA-MRSA, and USA300 CA-MRSA. Finally, significant antimicrobial resistance was seen in the region with variation in patterns depending on location and clonal type. For a more accurate assessment of MRSA epidemiology and burden, the Arab countries need to implement national surveillance systems.

Cervical osteomyelitis potentially caused by Campylobacter fetus.

Campylobacter fetus is a rare pathogen in humans. It mainly causes invasive infections in immunosuppressed patients. Herein, we report the first case of cervical vertebral osteomyelitis in a previously healthy man with a history of daily alcohol consumption. Treatment was given for six weeks with excellent clinical recovery and normalization of laboratory markers.

Are there monogenic hereditary forms of bladder cancer or only genetic susceptibilities?

Bladder cancer (BC) is the most common cancer involving the urinary system and the ninth most common cancer worldwide. Tobacco smoking is the most important environmental risk factor of BC. Several single nucleotide polymorphisms have been validated by genome-wide association studies as genetic risk factors for BC. However, the identification of DNA mismatch-repair genes, including MSH2 in Lynch syndrome and MUTYH in MUTYH-associated polyposis, raises the possibility of monogenic hereditary forms of BC. Moreover, other genetic mutations may play a key role in familial and hereditary transmissions of BC. Therefore, the aim of this review is to focus on the major hereditary syndromes involved in the development of BC and to report BC genetic susceptibilities established with genome-wide significance level.