Polymicrobial bloodstream infections in the neonatal intensive care unit are associated with increased mortality: a case-control study

Pammi, Mohan; Zhong, Dan-Ni; Johnson, Yvette R.; Revell, Paula A.; Versalovic, James

doi:10.1186/1471-2334-14-390

Cited by 80 publications

(68 citation statements)

References 29 publications

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“…This indicates a need to consider the role of host immunity and/or age in experimental virulence testing for NAC species. This is particularly important for polymicrobial infections involving Candida and Staphylococcus spp., which often are observed in neonatal ICU patients (46)(47)(48).…”

Section: Discussionmentioning

confidence: 99%

Morphology-Independent Virulence of Candida Species during Polymicrobial Intra-abdominal Infections with Staphylococcus aureus

et al. 2016

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c Intra-abdominal polymicrobial infections cause significant morbidity and mortality. An experimental mouse model of Candida albicans-Staphylococcus aureus intra-abdominal infection (IAI) results in 100% mortality by 48 to 72 h postinoculation, while monomicrobial infections are avirulent. Mortality is associated with robust local and systemic inflammation without a requirement for C. albicans morphogenesis. However, the contribution of virulence factors coregulated during the yeast-tohypha transition is unknown. This also raised the question of whether other Candida species that are unable to form hyphae are as virulent as C. albicans during polymicrobial IAI. Therefore, the purpose of this study was to evaluate the ability of non-albicans Candida (NAC) species with various morphologies and C. albicans transcription factor mutants (efg1/efg1 and cph1/cph1) to induce synergistic mortality and the accompanying inflammation. Results showed that S. aureus coinoculated with C. krusei or C. tropicalis was highly lethal, similar to C. albicans, while S. aureus-C. dubliniensis, S. aureus-C. parapsilosis, and S. aureus-C. glabrata coinoculations resulted in little to no mortality. Local and systemic interleukin-6 (IL-6) and prostaglandin E 2 (PGE 2 ) levels were significantly elevated during symptomatic and/or lethal coinfections, and hypothermia strongly correlated with mortality. Coinoculation with C. albicans strains deficient in the transcription factor Efg1 but not Cph1 reversed the lethal outcome. These results support previous findings and demonstrate that select Candida species, without reference to any morphological requirement, induce synergistic mortality, with IL-6 and PGE 2 acting as key inflammatory factors. Mechanistically, signaling pathways controlled by Efg1 are critical for the ability of C. albicans to induce mortality from an intra-abdominal polymicrobial infection. I ntra-abdominal infection (IAI) is a broad term used to describe numerous infections caused by the invasion of microorganisms into the abdominal cavity. These infections can range from appendicitis to complicated peritonitis and are initiated by microbes entering the abdominal cavity through a variety of routes, including bowel perforation, laparotomy, intestinal hernias, and insertion of medical devices such as peritoneal catheters (reviewed in reference 1). These infections often are polymicrobial in nature, which complicates diagnosis and treatment. Accordingly, infections with multiple microbes can result in amplified pathogenicity, also known as "infectious synergism" (2-4), which may accelerate disease progression or protect microbes from host responses (5), resulting in higher morbidity and mortality (6, 7).Polymicrobial IAIs involving fungi result in mortality rates between 50 and 75%, compared to 10 to 30% for polymicrobial bacterial infections (8-11). The majority of polymicrobial fungal IAIs are caused by Candida albicans (12, 13). However, IAIs caused by non-albicans Candida (NAC) species are becoming more common (14). C. al...

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Section: Discussionmentioning

confidence: 99%

Morphology-Independent Virulence of Candida Species during Polymicrobial Intra-abdominal Infections with Staphylococcus aureus

et al. 2016

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“…4a). For example, Staphylococcus aureus and C. albicans are often co-isolated from neonatal polymicrobial bloodstream infections 122 . Biofilms containing C. albicans and Streptococcus mutans or Streptococcus gordonii have been isolated from denture stomatitis and dental carries 123–126 , whereas C. albicans and Pseudomonas aeruginosa are commonly co-isolated from skin and lung infections 127 .…”

Section: Polymicrobial Biofilmsmentioning

confidence: 99%

Development and regulation of single- and multi-species Candida albicans biofilms

et al. 2017

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Candida albicans is among the most prevalent fungal species of the human microbiota and asymptomatically colonizes healthy individuals. However, it is also an opportunistic pathogen that can cause severe, and often fatal, bloodstream infections. The medical impact of C. albicans typically depends on its ability to form biofilms, which are closely packed communities of cells that attach to surfaces, such as tissues and implanted medical devices. In this Review, we provide an overview of the processes involved in the formation of C. albicans biofilms and discuss the core transcriptional network that regulates biofilm development. We also consider some of the advantages that biofilms provide to C. albicans in comparison with planktonic growth and explore polymicrobial biofilms that are formed by C. albicans and certain bacterial species.

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“…10 Likewise, animal models of bacterial coinfection are congruent with evidence in humans, supporting the concept that concurrent bacterial infection negatively impact outcome. 11,12 Though the mechanisms responsible for the worse outcome remain elusive, it has been suggested that infections can overstimulate the immune system and induce a state of immunoparalysis which enhances susceptibility to secondary infections. 13 …”

Section: Introductionmentioning

confidence: 99%

Potentiation and tolerance of toll-like receptor priming in human endothelial cells

Koch

Lamb

Hellman

et al. 2017

Translational Research

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Repeated challenge of lipopolysaccharide (LPS) alters the response to subsequent LPS exposures via modulation of toll-like receptor 4 (TLR4). Whether activation of other TLRs can modulate TLR4 responses, and vice versa, remains unclear. Specifically with regards to endothelial cells, a key component of innate immunity, the impact of TLR cross-modulation is unknown. We postulated that TLR2 priming (via Pam3Csk4) would inhibit TLR4-mediated responses while TLR3 priming (via Poly I:C) would enhance subsequent TLR4-inflammatory signaling. We studied human umbilical vein endothelial cells and neonatal dermal microvascular (HMVECs) endothelial cells. Cells were primed with a combination of Poly I:C (10 μg/ml), Pam3Csk4 (10 μg/ml), or LPS (100 ng/ml), then washed and allowed to rest. They were then rechallenged with either Poly I:C, Pam3Csk4 or LPS. Endothelial cells showed significant tolerance to repeated LPS challenge. Priming with Pam3Csk4 also reduced the response to secondary LPS challenge in both cell types, despite a reduced proinflammatory response to Pam3Csk4 in HMVECs compared to human umbilical vein endothelial cells. Poly I:C priming enhanced inflammatory and interferon producing signals upon Poly I:C or LPS rechallenge, respectively. Poly I:C priming also induced interferon regulatory factor 7, leading to enhancement of interferon production. Finally, both Poly I:C and LPS priming induced significant changes in receptor-interacting serine/threonine-protein kinase 1 activity. Pharmacological inhibition of receptor-interacting serine/threonine-protein kinase 1 or interferon regulatory factor 7 reduced the potentiated phenotype of TLR3 priming on TLR4 rechallenge. These results demonstrate that in human endothelial cells, prior activation of TLRs can have a significant impact on subsequent exposures and may contribute to the severity of the host response.

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Polymicrobial bloodstream infections in the neonatal intensive care unit are associated with increased mortality: a case-control study

Cited by 80 publications

References 29 publications

Morphology-Independent Virulence of Candida Species during Polymicrobial Intra-abdominal Infections with Staphylococcus aureus

Morphology-Independent Virulence of Candida Species during Polymicrobial Intra-abdominal Infections with Staphylococcus aureus

Development and regulation of single- and multi-species Candida albicans biofilms

Potentiation and tolerance of toll-like receptor priming in human endothelial cells

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