scholarly journals Characterization of cerebrospinal fluid (CSF) microbiota from patients with CSF shunt infection and reinfection using high throughput sequencing of 16S ribosomal RNAgenes

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0244643
Author(s):  
Kathryn B. Whitlock ◽  
Christopher E. Pope ◽  
Paul Hodor ◽  
Lucas R. Hoffman ◽  
David L. Limbrick ◽  
...  

Background Nearly 20% of patients with cerebrospinal fluid (CSF) shunt infection develop reinfection. It is unclear whether reinfections are caused by an organism previously present or are independent infection events. Objective We used bacterial culture and high throughput sequencing (HTS) of 16S ribosomal RNA (rRNA) genes to identify bacteria present in serial CSF samples obtained from children who failed CSF shunt infection treatment. We hypothesized that organisms that persist in CSF despite treatment would be detected upon reinfection. Design/methods Serial CSF samples were obtained from 6 patients, 5 with 2 infections and 1 with 3 infections; the study was limited to those for which CSF samples were available from the end of infection and beginning of reinfection. Amplicons of the 16S rRNA gene V4 region were sequenced. Taxonomic assignments of V4 sequences were compared with bacterial species identified in culture. Results Seven infection dyads averaging 13.5 samples per infection were analyzed. A median of 8 taxa [interquartile range (IQR) 5–10] were observed in the first samples from reinfection using HTS. Conventional culture correlated with high abundance of an organism by HTS in all but 1 infection. In 6 of 7 infection dyads, organisms identified by culture at reinfection were detected by HTS of culture-negative samples at the end of the previous infection. The median Chao-Jaccard abundance-based similarity index for matched infection pairs at end of infection and beginning of reinfection was 0.57 (IQR 0.07–0.87) compared to that for unmatched pairs of 0.40 (IQR 0.10–0.60) [p = 0.46]. Conclusion(s) HTS results were generally consistent with culture-based methods in CSF shunt infection and reinfection, and may detect organisms missed by culture at the end of infection treatment but detected by culture at reinfection. However, the CSF microbiota did not correlate more closely within patients at the end of infection and beginning of reinfection than between any two unrelated infections. We cannot reject the hypothesis that sequential infections were independent.

2018 ◽  
Vol 8 (3) ◽  
pp. 235-243 ◽  
Author(s):  
Tamara D Simon ◽  
Matthew P Kronman ◽  
Kathryn B Whitlock ◽  
Samuel R Browd ◽  
Richard Holubkov ◽  
...  

Abstract Background Previous studies of cerebrospinal fluid (CSF) shunt infection treatment have been limited in size and unable to compare patient and treatment characteristics by infecting organism. Our objective was to describe variation in patient and treatment characteristics for children with first CSF shunt infection, stratified by infecting organism subgroups outlined in the 2017 Infectious Disease Society of America’s (IDSA) guidelines. Methods We studied a prospective cohort of children <18 years of age undergoing treatment for first CSF shunt infection at one of 7 Hydrocephalus Clinical Research Network hospitals from April 2008 to December 2012. Differences between infecting organism subgroups were described using univariate analyses and Fisher’s exact tests. Results There were 145 children whose infections were diagnosed by CSF culture and addressed by IDSA guidelines, including 47 with Staphylococcus aureus, 52 with coagulase-negative Staphylococcus, 37 with Gram-negative bacilli, and 9 with Propionibacterium acnes. No differences in many patient and treatment characteristics were seen between infecting organism subgroups, including age at initial shunt, gender, race, insurance, indication for shunt, gastrostomy, tracheostomy, ultrasound, and/or endoscope use at all surgeries before infection, or numbers of revisions before infection. A larger proportion of infections were caused by Gram-negative bacilli when antibiotic-impregnated catheters were used at initial shunt placement (12 of 23, 52%) and/or subsequent revisions (11 of 23, 48%) compared with all other infections (9 of 68 [13%] and 13 of 68 [19%], respectively). No differences in reinfection were observed between infecting organism subgroups. Conclusions The organism profile encountered at infection differs when antibiotic-impregnated catheters are used, with a higher proportion of Gram-negative bacilli. This warrants further investigation given increasing adoption of antibiotic-impregnated catheters.


1987 ◽  
Vol 8 (2) ◽  
pp. 67-70 ◽  
Author(s):  
Janara J. Younger ◽  
James C.H. Simmons ◽  
Fred F. Barrett

AbstractWe determined the operative related cerebrospinal fluid (CSF) shunt infection rates for our institution over a 3-year period (1982 to 1984) using strictly defined numerator and denominator data. The minimum post-operative follow-up period was 12 months. The average surgical infection risk for a CSF shunt procedure at our institution during the study period was 13.3%. Annual infection rates were relatively constant (13.8%, 13.2% and 12.9%), however both quarterly (5.7% to 23.3%) and surgeon-specific (5.7% to 22.8%) rates varied widely. Infection rates calculated by using “traditional” numerator and denominator data were considerably lower (6.5% to 9.2%).Operative related CSF shunt infection rates should be determined by utilizing strictly defined numerator and denominator values in order to allow valid comparisons of published rates.


2007 ◽  
Vol 22 (4) ◽  
pp. 1-4 ◽  
Author(s):  
Daniel M. Sciubba ◽  
Li-Mei Lin ◽  
Graeme F. Woodworth ◽  
Matthew J. McGirt ◽  
Benjamin Carson ◽  
...  

Object Antibiotic-impregnated shunt (AIS) systems may decrease the incidence of cerebrospinal fluid (CSF) shunt infections. However, there is a reluctance to use AIS components because of their increased cost. In the present study the authors evaluated factors contributing to the medical costs associated with the treatment of CSF shunt infections in a hydrocephalic pediatric population, those implanted with AIS systems compared with those implanted with standard shunt systems. Methods The authors retrospectively reviewed data obtained in all pediatric patients who had undergone CSF shunt insertion at their institution over a 3-year period. All patients were followed up for 12 months after surgery. The independent association between AIS catheter use and subsequent shunt infection was assessed by performing a multivariate proportional hazards regression analysis. Factors contributing to the medical costs associated with shunt infection were evaluated. Results Two hundred eleven pediatric patients underwent 353 shunting procedures. Two hundred eight shunts (59%) were placed with nonimpregnated catheters and 145 shunts (41%) were placed with AIS catheters. Twenty-five patients (12%) with non-AIS catheters experienced shunt infection, whereas only two patients (1.4%) with AIS catheters had a shunt infection within the 6-month follow-up period (p < 0.01). Among infected patients, infected patients with standard shunt components had a longer average hospital stay, more inpatient complications related to infection treatment, and more multiple organism infections and multiple antibiotic regimens, compared with those with AIS components. Conclusions Although individual AIS components are more expensive than standard ones, factors contributing to medical costs are fewer in pediatric patients with infected shunts when the components are antibiotic-impregnated rather than standard.


Author(s):  
Paul Hodor ◽  
Christopher E. Pope ◽  
Kathryn B. Whitlock ◽  
Lucas R. Hoffman ◽  
David L. Limbrick ◽  
...  

Understanding the etiology of cerebrospinal fluid (CSF) shunt infections and reinfections requires detailed characterization of associated microorganisms. Traditionally, identification of bacteria present in the CSF has relied on culture methods, but recent studies have used high throughput sequencing of 16S rRNA genes. Here we evaluated the method of shotgun DNA sequencing for its potential to provide additional genomic information. CSF samples were collected from 3 patients near the beginning and end of each of 2 infection episodes. Extracted total DNA was sequenced by: (1) whole genome amplification followed by shotgun sequencing (WGA) and (2) high-throughput sequencing of the 16S rRNA V4 region (16S). Taxonomic assignments of sequences from WGA and 16S were compared with one another and with conventional microbiological cultures. While classification of bacteria was consistent among the 3 approaches, WGA provided additional insights into sample microbiological composition, such as showing relative abundances of microbial versus human DNA, identifying samples of questionable quality, and detecting significant viral load in some samples. One sample yielded sufficient non-human reads to allow assembly of a high-quality Staphylococcus epidermidis genome, denoted CLIMB1, which we characterized in terms of its MLST profile, gene complement (including putative antimicrobial resistance genes), and similarity to other annotated S. epidermidis genomes. Our results demonstrate that WGA directly applied to CSF is a valuable tool for the identification and genomic characterization of dominant microorganisms in CSF shunt infections, which can facilitate molecular approaches for the development of better diagnostic and treatment methods.


2019 ◽  
Vol 23 (5) ◽  
pp. 577-585
Author(s):  
Tamara D. Simon ◽  
Matthew P. Kronman ◽  
Kathryn B. Whitlock ◽  
Samuel R. Browd ◽  
Richard Holubkov ◽  
...  

OBJECTIVECSF shunt infection treatment requires both surgical and antibiotic decisions. Using the Hydrocephalus Clinical Research Network (HCRN) Registry and 2004 Infectious Diseases Society of America (IDSA) guidelines that were not proactively distributed to HCRN providers, the authors previously found high adherence to surgical recommendations but poor adherence to intravenous (IV) antibiotic duration recommendations. In general, IV antibiotic duration was longer than recommended. In March 2017, new IDSA guidelines expanded upon the 2004 guidelines by including recommendations for selection of specific antibiotics. The objective of this study was to describe adherence to both 2004 and 2017 IDSA guideline recommendations for CSF shunt infection treatment, and to report reinfection rates associated with adherence to guideline recommendations.METHODSThe authors investigated a prospective cohort of children younger than 18 years of age who underwent treatment for first CSF shunt infection at one of 7 hospitals from April 2008 to December 2012. CSF shunt infection was diagnosed by recovery of bacteria from CSF culture (CSF-positive infection). Adherence to 2004 and 2017 guideline recommendations was determined. Adherence to antibiotics was further classified as longer or shorter duration than guideline recommendations. Reinfection rates with 95% confidence intervals (CIs) were generated.RESULTSThere were 133 children with CSF-positive infections addressed by 2004 IDSA guideline recommendations, with 124 at risk for reinfection. Zero reinfections were observed among those whose treatment was fully adherent (0/14, 0% [95% CI 0%–20%]), and 15 reinfections were observed among those whose infection treatment was nonadherent (15/110, 14% [95% CI 8%–21%]). Among the 110 first infections whose infection treatment was nonadherent, 74 first infections were treated for a longer duration than guidelines recommended and 9 developed reinfection (9/74, 12% [95% CI 6%–22%]). There were 145 children with CSF-positive infections addressed by 2017 IDSA guideline recommendations, with 135 at risk for reinfection. No reinfections were observed among children whose treatment was fully adherent (0/3, 0% [95% CI 0%–64%]), and 18 reinfections were observed among those whose infection treatment was nonadherent (18/132, 14% [95% CI 8%–21%]).CONCLUSIONSThere is no clear evidence that either adherence to IDSA guidelines or duration of treatment longer than recommended is associated with reduction in reinfection rates. Because IDSA guidelines recommend shorter IV antibiotic durations than are typically used, improvement efforts to reduce IV antibiotic use in CSF shunt infection treatment can and should utilize IDSA guidelines.


2017 ◽  
Vol 24 (01) ◽  
pp. 110-115 ◽  
Author(s):  
Dr. Muhammad Sohaib Anwer ◽  
Dr. Muhammad Ali Waqas ◽  
Dr. Atta ur-Rehman Khan

Neurosurgery ◽  
2006 ◽  
Vol 58 (4) ◽  
pp. 657-665 ◽  
Author(s):  
Erwin M. Brown ◽  
Richard J. Edwards ◽  
Ian K. Pople

Abstract OBJECTIVE: In patients with cerebrospinal fluid (CSF) shunt infection, removal of the shunt and antibiotic administration is the current standard of care. In 1986, we developed a protocol for the conservative management of patients with infected but functioning shunts. Treatment was based on the administration of a combination of intraventricular and systemic antibiotics. Intraventricular antibiotics were instilled via a separate access device. The purpose of this report is to describe our experience with this therapeutic intervention. METHODS: An observational study of all patients treated for CSF shunt infection between 1986 and 2003 was undertaken. Cure was defined by sterile CSF after completion of therapy and sterile shunt components at next revision or long-term freedom from recurrent infection (follow-up period, 6–88 mo). RESULTS: In total, 43 of 122 patients with CSF shunt infections were treated conservatively according to our protocol. Overall, 84% of these patients were cured, with a 92% success rate for patients with infections caused by bacteria other than Staphylococcus aureus. This included 30 coagulase-negative staphylococcal infections, of which two were treatment failures. We abandoned conservative treatment of patients with Staphylococcus aureus infections after early experience demonstrated that the success rate (four treatment failures in seven patients) was markedly lower than that for other pathogens. During the treatment and follow-up periods, there were three deaths, two of which were unrelated to shunt infection; treatment failure could not be completely excluded in the remaining patient. There was no toxicity related to intraventricular antibiotic administration. The incidence of shunt blockage among patients who were treated conservatively was not significantly different from that among a large cohort of patients with uninfected shunts. Ten patients received part of their courses of treatment as outpatients. CONCLUSION: The success rate of conservative management of patients with CSF shunt infections caused by coagulase-negative staphylococci is comparable with those in the published literature for patients treated conventionally. This form of management avoids surgical intervention, with its attendant risks, and is safe.


Atmosphere ◽  
2020 ◽  
Vol 11 (8) ◽  
pp. 802
Author(s):  
Hokyung Song ◽  
Ian Crawford ◽  
Jonathan Lloyd ◽  
Clare Robinson ◽  
Christopher Boothman ◽  
...  

Primary biological aerosols often include allergenic and pathogenic microorganisms posing potential risks to human health. Moreover, there are airborne plant and animal pathogens that may have ecological and economic impact. In this study, we used high-throughput sequencing techniques (Illumina, MiSeq) targeting the 16S rRNA genes of bacteria and the 18S rRNA genes of eukaryotes, to characterize airborne primary biological aerosols. We used a filtration system on the UK Facility for Airborne Atmospheric Measurements (FAAM) research aircraft to sample a range of primary biological aerosols across southern England overflying surface measurement sites from Chilbolton to Weybourne. We identified 30 to 60 bacterial operational taxonomic units (OTUs) and 108 to 224 eukaryotic OTUs per sample. Moreover, 16S rRNA gene sequencing identified significant numbers of genera that have not been found in atmospheric samples previously or only been described in limited number of atmospheric field studies, which are rather old or published in local journals. This includes the genera Gordonia, Lautropia, and Psychroglaciecola. Some of the bacterial genera found in this study include potential human pathogens, for example, Gordonia, Sphingomonas, Chryseobacterium, Morganella, Fusobacterium, and Streptococcus. 18S rRNA gene sequencing showed Cladosporium to be the major genus in all of the samples, which is a well-known allergen and often found in the atmosphere. There were also genetic signatures of potentially allergenic taxa; for example, Pleosporales, Phoma, and Brassicales. Although there was no significant clustering of bacterial and eukaryotic communities depending on the sampling location, we found meteorological factors explaining significant variations in the community composition. The findings in this study support the application of DNA-based sequencing technologies for atmospheric science studies in combination with complementary spectroscopic and microscopic techniques for improved identification of primary biological aerosols.


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