Patterns of bacteraemia aetiology
Authors: Alan Cross, Myron M Levine
Journal: The Lancet Infectious Diseases (2017)

Bloodstream infections are a leading cause of morbidity and mortality in both high-income and lower-income countries, but the causative organisms and risk factors differ. Human beings coexist with diverse bacterial flora on their skin and their nasal, pharyngeal, and gastrointestinal mucosae. Physical barriers and non-specific immune defences keep these bacteria in check. However, various primary pathogens can invade via the respiratory mucosa (eg, some Streptococcus pneumoniae serotypes) or gastrointestinal (Salmonella Typhi) mucosa or integument (Staphylococcus aureus), then enter the bloodstream and provoke clinical syndromes such as sepsis, febrile bacteraemia, meningitis, or enteric fever. In The Lancet Infectious Diseases, Patrick Musicha and colleagues1Musicha P Cornick J E Bar-Neev N et al.Trends in antimicrobial resistance in bloodstream infection isolates at a large urban hospital in Malawi (1998–2016): a surveillance study.Lancet Infec Dis. 2017; (published online August 14.)http://dx.doi.org/10.1016/S1473-3099(17)30394-8PubMed Google Scholar report that pathogens often isolated from the blood of US patients in the first decades of the 20th century, including S Typhi, S pneumoniae type 1, and Streptococcus pyogenes,2McGowan JE Barnes MW Finland M Bacteremia at Boston City Hospital: occurrence and mortality during 12 selected years (1935–1972), with special reference to hospital-acquired cases.J Infect Dis. 1975; 132: 316-335Crossref PubMed Scopus (384) Google Scholar, 3Keefer CS The clinical significance of bacteremia.NY State Med J. 1941; 41: 976-981Google Scholar were common in Malawian patients in the first decades of the 21st century. In low-income countries such as Malawi, where 45% of the population are children younger than 15 years, household crowding, inadequate sanitation, and lack of potable water foster the transmission of pathogens such as S Typhi, non-typhoidal salmonella, and invasive S pneumoniae serotypes.1Musicha P Cornick J E Bar-Neev N et al.Trends in antimicrobial resistance in bloodstream infection isolates at a large urban hospital in Malawi (1998–2016): a surveillance study.Lancet Infec Dis. 2017; (published online August 14.)http://dx.doi.org/10.1016/S1473-3099(17)30394-8PubMed Google Scholar Bloodstream infections can be categorised as hospital-onset (≥48 h after admission) or community-onset (<48 h after admission). In high-income countries, the proportion of patients with health-care exposure prior to the bacteraemic illness is increasing. This includes visits to outpatient facilities (eg, haemodialysis, chemotherapy) where patients often undergo urinary and vascular catherisation; others have internal medical devices or spend time in nursing homes. Consequently, a subgroup of community-onset bloodstream infections has emerged—ie, health-care-associated community-onset bloodstream infections. These patients, who usually have co-morbid conditions (eg, diabetes, cancer, organ failure), have bacteraemia with Gram-negative bacilli such as Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and S aureus and have poorer prognoses than patients with community-onset bloodstream infections not associated with access to health care.3Keefer CS The clinical significance of bacteremia.NY State Med J. 1941; 41: 976-981Google Scholar Musicha and colleagues,1Musicha P Cornick J E Bar-Neev N et al.Trends in antimicrobial resistance in bloodstream infection isolates at a large urban hospital in Malawi (1998–2016): a surveillance study.Lancet Infec Dis. 2017; (published online August 14.)http://dx.doi.org/10.1016/S1473-3099(17)30394-8PubMed Google Scholar, report the burden of bloodstream infections in children and adults in an urban hospital in Blantyre, Malawi, and provide bacteriological findings and antibiotic susceptibility data over a 17-year period. Because blood cultures were obtained only on admission of patients presenting with fever, and the average hospital stay was less than 5 days, the authors conclude that these samples represent community-onset bloodstream infections. As the incidence of bacteraemia decreased during the study period, resistance to multiple antibiotics increased. Non-typhoidal salmonella was the leading cause of bacteraemia for more than a decade, whereas S Typhi emerged later in the study, in epidemic fashion. Gram-positive organisms were less common. Following routine infant immunisation with multivalent pneumococcal conjugate vaccine, the proportion of bacteraemic patients yielding S pneumoniae decreased from 17% in 1998–2001, to 8% in 2010–14. S aureus was the second most common cause of bloodstream infections (6·4%) in Balantyre with less than 10% meticillin-resistant S aureus (MRSA). MRSA has only been detected since 2005 in sub-Saharan Africa. Klebsiella (4·4% of bloodstream infections) and E coli (8·6% of bloodstream infections) were relatively common, particularly in patients older than 55 years, but P aeruginosa was infrequent. Most fungal blood infections were cryptococcus, presumably reflecting the prevalence of HIV infections. By contrast with community-onset bloodstream infections in low-income countries, the leading causes of community-onset bloodstream infections in high-income countries are E coli, S aureus, S pneumoniae, and K pneumoniae.5Laupland KB Church DL Population-based epidemiology and microbiology of community-onset bloodstream infections.Clin Microbiol Rev. 2014; 27: 647-664Crossref PubMed Scopus (163) Google Scholar, 6Anderson DJ Moehring RW Sloane R et al.Bloodstream infections in community hospitals in the 21st century: a multicenter cohort study.PLoS One. 2014; 9: e91713Crossref PubMed Scopus (96) Google Scholar Health-care-associated community-onset bloodstream infections account for 33–50% of all community-onset bloodstream infections in high-income countries, with non-salmonella Gram-negative bacilli as leading pathogens but Gram-positive cocci, particularly S aureus and S epidermidis,7Takeshita N Kawamura I Kurai H et al.Unique characteristics of community-onset healthcare-associated bloodstream infections: a multi-centre prospective surveillance study of bloodstream infections in Japan.J Hosp Infect. 2017; 96: 29-34Summary Full Text Full Text PDF PubMed Scopus (20) Google Scholar having more prominence. The most alarming observation of community-onset bloodstream infections in low-income countries is the large increase in antimicrobial resistance, mirroring the trends in high-income countries. In Malawi, there were noticeable increases in extended spectrum beta-lactamase-producing and fluoroquinolone-resistant Gram-negative bacilli. Many such infections were locally untreatable, with resistance to all tested antibiotics. Antimicrobial resistance was reported even to drugs that are not routinely used, such as gentamicin. Although antibiotics can be bought without prescriptions in Malawi, ceftriaxone and ciprofloxacin—mainstays of empirical therapy for febrile patients—were not routinely available outside Malawi's four hospitals. It is difficult to know the extent of antibiotic usage in low-income countries and how that contributes to increasing antimicrobial resistance. If antimicrobial resistance is emerging in the absence of extensive use of particular drugs, we should investigate the mechanisms responsible. The study by Musicha and colleagues1Musicha P Cornick J E Bar-Neev N et al.Trends in antimicrobial resistance in bloodstream infection isolates at a large urban hospital in Malawi (1998–2016): a surveillance study.Lancet Infec Dis. 2017; (published online August 14.)http://dx.doi.org/10.1016/S1473-3099(17)30394-8PubMed Google Scholar emphasises the need to improve diagnostic capabilities in country hospitals in low-income countries and to conduct surveillance in diverse geographic locales. Studies from both low-income and high-income countries attest to the relentless emergence of antimicrobial resistance globally; unchecked, this could hasten the arrival of what WHO has referred to as a post-antibiotic era. MML reports receipt of an award to develop and perform early clinical trials of a Trivalent Salmonella Enteritidis/Salmonella Typhimurium/Salmonella Typhi Vi-conjugate vaccine, as a principle investigator. AC reports no competing interests. Trends in antimicrobial resistance in bloodstream infection isolates at a large urban hospital in Malawi (1998–2016): a surveillance studyThe rapid expansion of ESBL and fluoroquinolone resistance among common Gram-negative pathogens, and the emergence of MRSA, highlight the growing challenge of bloodstream infections that are effectively impossible to treat in this resource-limited setting. Full-Text PDF Open Access