Relationship between the inoculum dose of Streptococcus pneumoniae and pneumonia onset in a rabbit model

Yershov, A. L.; Jordan, Bryan S.; Guymon, Charles H; Dubick, Michael A.

doi:10.1183/09031936.05.00091904

Cited by 19 publications

(17 citation statements)

References 29 publications

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“…Lastly, this study used a starting inoculum of ϳ10 6 CFU/ml, which allowed isolates to grow ϳ10 9 CFU/ml over the course of a few hours. While this starting inoculum is well above the threshold for onset of pneumonia in animal infection models (46), it is well established that vancomycin and beta-lactam antibiotics can portray reduced bactericidal activity in the presence of higher inoculums (29); therefore, the observed results may not be applicable to scenarios that begin with a higher inoculum than ϳ10 6 CFU/ml. In this in vitro experiment, ceftaroline 600 mg q8h achieved the greatest killing against these S. aureus isolates and warrants further investigation for the treatment of pneumonia.…”

Section: Discussionmentioning

confidence: 46%

In Vitro Activity of Human-Simulated Epithelial Lining Fluid Exposures of Ceftaroline, Ceftriaxone, and Vancomycin against Methicillin-Susceptible and -Resistant Staphylococcus aureus

MacVane

Nicolau

et al. 2014

Antimicrob Agents Chemother

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bStaphylococcus aureus, including methicillin-susceptible (MSSA) and -resistant (MRSA) strains, is an important pathogen of bacterial pneumonia. As antibiotic concentrations at the site of infection are responsible for killing, we investigated the activity of human-simulated epithelial lining fluid (ELF) exposures of three antibiotics (ceftaroline, ceftriaxone, and vancomycin) commonly used for treatment of S. aureus pneumonia. An in vitro pharmacodynamic model was used to simulate ELF exposures of vancomycin (1 g every 12 h [q12h]), ceftaroline (600 mg q12h and q8h), and ceftriaxone (2 g q24h and q12h). Four S. aureus isolates (2 MSSA and 2 MRSA) were evaluated over 72 h with a starting inoculum of ϳ10 6 CFU/ml. Time-kill curves were constructed, and microbiological response (change in log 10 CFU/ml from 0 h and the area under the bacterial killing and regrowth curve [AUBC]) was assessed in duplicate. The change in 72-h log 10 CFU/ml was largest for ceftaroline q8h (reductions of >3 log 10 CFU/ml against all strains). This regimen also achieved the lowest AUBC against all organisms (P < 0.05). Vancomycin produced reliable bacterial reductions of 0.9 to 3.3 log 10 CFU/ml, while the activity of ceftaroline q12h was more variable (reductions of 0.2 to 2.3 log 10 CFU/ml against 3 of 4 strains). Both regimens of ceftriaxone were poorly active against MSSA tested (0.1 reduction to a 1.8-log 10 CFU/ml increase). Against these S. aureus isolates, ELF exposures of ceftaroline 600 mg q8h exhibited improved antibacterial activity compared with ceftaroline 600 mg q12h and vancomycin, and therefore, this q8h regimen deserves further evaluation for the treatment of bacterial pneumonia. These data also suggest that ceftriaxone should be avoided for S. aureus pneumonia.

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Section: Discussionmentioning

confidence: 46%

In Vitro Activity of Human-Simulated Epithelial Lining Fluid Exposures of Ceftaroline, Ceftriaxone, and Vancomycin against Methicillin-Susceptible and -Resistant Staphylococcus aureus

MacVane

Nicolau

et al. 2014

Antimicrob Agents Chemother

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“…Using a polystyrene surface as a fomite model, we demonstrate the environmental survival of S. pneumoniae over a period of 4 weeks. Although there was a decline in bacterial survival over time, the median total concentration of viable cells even after 14 days of desiccation fell within a previously suggested 50% infective dose (ID 50 ) range for invasive pneumococcal disease (IPD) for this pathogen (37, 38). Since more bacteria are generally needed for invasive disease than for intranasal inoculation, this number may be sufficient for nasopharyngeal colonization, the first step toward infection (39).…”

Section: Discussionmentioning

confidence: 62%

Streptococcus pneumoniae Is Desiccation Tolerant and Infectious upon Rehydration

Walsh

Camilli

2011

mBio

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Streptococcus pneumoniae (pneumococcus) is a frequent colonizer of the nasopharynx and one of the leading causative agents of otitis media, pneumonia, and meningitis. The current literature asserts that S. pneumoniae is transmitted person to person via respiratory droplets; however, environmental surfaces (fomites) have been linked to the spread of other respiratory pathogens. Desiccation tolerance has been to shown to be essential for long-term survival on dry surfaces. This study investigated the survival and infectivity of S. pneumoniae following desiccation under ambient conditions. We recovered viable bacteria after all desiccation periods tested, ranging from 1 h to 4 weeks. Experiments conducted under nutrient limitation indicate that desiccation is a condition separate from starvation. Desiccation of an acapsular mutant and 15 different clinical isolates shows that S. pneumoniae desiccation tolerance is independent of the polysaccharide capsule and is a species-wide phenomenon, respectively. Experiments demonstrating that nondesiccated and desiccated S. pneumoniae strains colonize the nasopharynx at comparable levels, combined with their ability to survive long-term desiccation, suggest that fomites may serve as alternate sources of pneumococcal infection.

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“…P. aeruginosa pneumonia was defined as the conjunction of a macroscopic pulmonary inflammation and a lung bacterial count Ͼ10 4 CFU per lung (a normal rat lung weighs Ͻ1 g) (20).…”

Section: In Vivo Experimentsmentioning

confidence: 99%

Candida albicans impairs macrophage function and facilitates Pseudomonas aeruginosa pneumonia in rat*

Roux

Gaudry

Dreyfuss

et al. 2009

Critical Care Medicine

117

102

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C. albicans impedes alveolar macrophage ROS production and is correlated with an increase of P. aeruginosa pneumonia prevalence in rats. These results highlight the previously overlooked impact of airway fungal colonization on lung bacterial infection, and indicate the need for studies on the potential for antifungal therapy to prevent the onset of ventilator-associated pneumonia caused by P. aeruginosa.

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Relationship between the inoculum dose of Streptococcus pneumoniae and pneumonia onset in a rabbit model

Cited by 19 publications

References 29 publications

In Vitro Activity of Human-Simulated Epithelial Lining Fluid Exposures of Ceftaroline, Ceftriaxone, and Vancomycin against Methicillin-Susceptible and -Resistant Staphylococcus aureus

In Vitro Activity of Human-Simulated Epithelial Lining Fluid Exposures of Ceftaroline, Ceftriaxone, and Vancomycin against Methicillin-Susceptible and -Resistant Staphylococcus aureus

Streptococcus pneumoniae Is Desiccation Tolerant and Infectious upon Rehydration

Candida albicans impairs macrophage function and facilitates Pseudomonas aeruginosa pneumonia in rat*

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