Bloodstream Infections in Hospitalized Children

Larrú, Beatriz; Gong, Wu; Vendetti, Neika; Sullivan, Kaede V.; Localio, Russell; Zaoutis, Theoklis E.; Gerber, Jeffrey S.

doi:10.1097/inf.0000000000001057

Cited by 55 publications

(26 citation statements)

References 14 publications

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“…Finally, many gram-negative bloodstream infections are part of a polymicrobial or complex process such as an intra-abdominal infection, necessitating broad-spectrum therapy even when the identified pathogen could be more narrowly treated. However, with low resistance rates among gram-negative organisms in children’s hospitals in general [36, 37] as well as lower mortality from sepsis [38, 39], the opportunity for early de-escalation and reduction in selection pressure is great. Expansion of rapid testing to include gram-negative resistance markers is critical.…”

Section: Discussionmentioning

confidence: 99%

A Retrospective Study of the Impact of Rapid Diagnostic Testing on Time to Pathogen Identification and Antibiotic Use for Children with Positive Blood Cultures

et al. 2016

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IntroductionRapid identification of bloodstream pathogens provides crucial information that can improve the choice of antimicrobial therapy for children. Previous impact studies have primarily focused on adults. Our objective was to evaluate the impact of rapid testing in a children’s hospital on time to organism identification and antibiotic use in the setting of an established antimicrobial stewardship program.MethodsWe conducted a retrospective study over three consecutive time periods (spanning January 2013–August 2015) as our hospital sequentially introduced two rapid testing methods for positive blood cultures. An antimicrobial stewardship program was active throughout the study. In the baseline period, no rapid diagnostic methods were routinely utilized. In the second period (PNAFISH), a fluorescent in situ hybridization test was implemented for gram-positive organisms and in the third a rapid multiplex PCR (rmPCR) test was employed. For children with positive blood cultures, time to organism identification use and duration of select antimicrobial therapies were compared between periods.ResultsPositive blood cultures were analyzed. Median overall time to organism identification was 23, 11, and 0 h in the baseline, PNAFISH, and rmPCR periods, respectively (p < 0.001 for both PNAFISH and rmPCR vs. baseline). For gram-negative organisms, only rmPCR performed significantly faster than baseline (p < 0.001). The duration of vancomycin use for coagulase-negative staphylococci was shorter in both the PNAFISH and rmPCR periods (mean 31 h in the baseline period, 12 and 14 h in the PNAFISH and rmPCR periods, respectively). For MSSA bacteremia, use of vancomycin was significantly decreased only in the rmPCR period (32% of patients vs. 64 and 72% in the baseline and PNAFISH periods; mean duration of 9 h vs. 30 and 26 h). There was no difference in use or duration of broad-spectrum gram-negative therapy across the three time periods.ConclusionRapid diagnostic testing for children with positive blood cultures results in faster time to identification and can influence antibiotic prescribing in the setting of active antimicrobial stewardship particularly for gram-positive pathogens.FundingMerck.

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Section: Discussionmentioning

confidence: 99%

A Retrospective Study of the Impact of Rapid Diagnostic Testing on Time to Pathogen Identification and Antibiotic Use for Children with Positive Blood Cultures

et al. 2016

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“…Furthermore, its frequent occurrence in the skin microbiome makes it a prime candidate for hospital-acquired infection. Coagulase-negative Staphylococci (CoNS), of which S. epidermidis is the predominant species, are the most common cause of bloodstream and device-related infections [2,3]. The primary virulence factor for S. epidermidis is its ability to form robust biofilms [4].…”

Section: Introductionmentioning

confidence: 99%

Functional consequences of B-repeat sequence variation in the staphylococcal biofilm protein Aap: deciphering the assembly code

Shelton

Conrady

Herr

2017

Biochemical Journal

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Staphylococcus epidermidis is an opportunistic pathogen that can form robust biofilms that render the bacteria resistant to antibiotic action and immune responses. Intercellular adhesion in S. epidermidis biofilms is mediated by the cell wall-associated Accumulation-Associated Protein (Aap), via zinc-mediated self-assembly of its B-repeat region. This region contains up to 17 nearly-identical sequence repeats, with each repeat assumed to be functionally equivalent. However, Aap B-repeats exist as two subtypes, defined by a cluster of consensus or variant amino acids. These variable residues are positioned near the zinc-binding (and dimerization) site and the stability determinant for the B-repeat fold. We have characterized four B-repeat constructs to assess the functional relevance of the two Aap B-repeat subtypes. Analytical ultracentrifugation experiments demonstrated that constructs with the variant sequence show reduced or absent Zn2+-induced dimerization. Likewise, circular dichroism thermal denaturation experiments showed that the variant sequence could significantly stabilize the fold, depending on its location within the construct. Crystal structures of three of the constructs revealed that the side chains from the variant sequence form an extensive bonding network that can stabilize the fold. Furthermore, altered distribution of charged residues between consensus and variant sequences changes the electrostatic potential in the vicinity of the Zn2+ binding site, providing a mechanistic explanation for the loss of zinc-induced dimerization in the variant constructs. These data suggest an assembly code that defines preferred oligomerization modes of the B-repeat region of Aap and a slip-grip model for initial contact and firm intercellular adhesion during biofilm formation.

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“…In hospitals, Staphylococcus aureus , a Gram-positive bacteria, has become the most commonly isolated pathogen involved in serious diseases (Emori and Gaynes, 1993), and the emergence of methicillin-resistant S. aureus (MRSA) strains worldwide poses serious risks to patients with immunological diseases (Orrett and Land, 2006; Boucher et al, 2009). Several antibiotics, including mupirocin (MU) and linezolid (LN), have proven effective against both methicillin-resistant and non-resistant strains of S. aureus (Tallón et al, 2002; Larru et al, 2016). MU is one of the most frequently used antibiotics for topical treatment of S. aureus skin infections (Saderi et al, 2008), while LN is more commonly administered intravenously (Cattaneo et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

“…Although results vary depending on the studied strain and its geographical localization, several recent studies suggest that the antibiotic resistance of S. aureus is on the rise, underscoring the need for new treatment strategies (Orrett, 2008; Saderi et al, 2008; Gu et al, 2013; Gostev et al, 2015; Larru et al, 2016). …”

Section: Introductionmentioning

confidence: 99%

Bactericidal Effect of Photodynamic Therapy, Alone or in Combination with Mupirocin or Linezolid, on Staphylococcus aureus

et al. 2017

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Antibiotic treatments frequently fail due to the development of antibiotic resistance, underscoring the need for new treatment strategies. Antimicrobial photodynamic therapy (aPDT) could constitute an alternative therapy. In bacterial suspensions of Staphylococcus aureus, which is commonly implicated in cutaneous and mucosal infections, we evaluated the in vitro efficacy of aPDT, using the photosensitizing agents rose bengal (RB) or methylene blue (MB), alone or combined with the antibiotics mupirocin (MU) or linezolid (LN). RB or MB, at concentrations ranging from 0.03 to 10 μg/ml, were added to S. aureus ATCC 29213 suspensions containing >108 cells/ml, in the absence or presence of MU or LN (1 or 10 μg/ml). Suspensions were irradiated with a white metal halide (λ 420–700 nm) or light-emitting diode lamp (λ 515 and λ 625 nm), and the number of viable bacteria quantified by counting colony-forming units (CFU) on blood agar. Addition of either antibiotic had no significant effect on the number of CFU/ml. By contrast, RB-aPDT and MB-aPDT effectively inactivated S. aureus, as evidenced by a 6 log10 reduction in bacterial growth. In the presence of MU or LN, the same 6 log10 reduction was observed in response to aPDT, but was achieved using significantly lower concentrations of the photosensitizers RB or MB. In conclusion, the combination of MU or LN and RB/MB-aPDT appears to exert a synergistic bactericidal effect against S. aureus in vitro.

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Bloodstream Infections in Hospitalized Children

Cited by 55 publications

References 14 publications

A Retrospective Study of the Impact of Rapid Diagnostic Testing on Time to Pathogen Identification and Antibiotic Use for Children with Positive Blood Cultures

A Retrospective Study of the Impact of Rapid Diagnostic Testing on Time to Pathogen Identification and Antibiotic Use for Children with Positive Blood Cultures

Functional consequences of B-repeat sequence variation in the staphylococcal biofilm protein Aap: deciphering the assembly code

Bactericidal Effect of Photodynamic Therapy, Alone or in Combination with Mupirocin or Linezolid, on Staphylococcus aureus

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