Kaede V. Sullivan

Reconsidering contact precautions for endemic methicillin-resistant staphylococcus aureus and vancomycin-resistant enterococcus

BACKGROUND Whether contact precautions (CP) are required to control the endemic transmission of methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE) in acute care hospitals is controversial in light of improvements in hand hygiene, MRSA decolonization, environmental cleaning and disinfection, fomite elimination, and chlorhexidine bathing. OBJECTIVE To provide a framework for decision making around use of CP for endemic MRSA and VRE based on a summary of evidence related to use of CP, including impact on patients and patient care processes, and current practices in use of CP for MRSA and VRE in US hospitals. DESIGN A literature review, a survey of Society for Healthcare Epidemiology of America Research Network members on use of CP, and a detailed examination of the experience of a convenience sample of hospitals not using CP for MRSA or VRE. PARTICIPANTS Hospital epidemiologists and infection prevention experts. RESULTS No high quality data support or reject use of CP for endemic MRSA or VRE. Our survey found more than 90% of responding hospitals currently use CP for MRSA and VRE, but approximately 60% are interested in using CP in a different manner. More than 30 US hospitals do not use CP for control of endemic MRSA or VRE. CONCLUSIONS Higher quality research on the benefits and harms of CP in the control of endemic MRSA and VRE is needed. Until more definitive data are available, the use of CP for endemic MRSA or VRE in acute care hospitals should be guided by local needs and resources.

Rapid Detection of Gram-Positive Organisms by Use of the Verigene Gram-Positive Blood Culture Nucleic Acid Test and the BacT/Alert Pediatric FAN System in a Multicenter Pediatric Evaluation

ABSTRACT Assays that expedite the reporting of organism identification and antibiotic susceptibility status in positive blood cultures can fast track interventions that improve clinical outcomes. We evaluated the Verigene Gram-positive blood culture nucleic acid test (BC-GP) in two pediatric hospitals. Positive BacT/Alert Pediatric FAN blood cultures with Gram-positive organisms were tested using the BC-GP in tandem with routine laboratory procedures. To test organisms underrepresented in the clinical blood culture evaluation, blood culture bottles were spiked with diluted organism suspensions at concentrations of 10 to 100 CFU per milliliter. A total of 249 Gram-positive bacterial isolates were recovered from 242 blood cultures. The BC-GP detected Staphylococcus aureus, methicillin-susceptible S. aureus, and methicillin-resistant S. aureus with sensitivities of 100%, 99%, and 100% and specificities of 100%, 100%, and 99.5%, respectively. The BC-GP detected Staphylococcus epidermidis, methicillin-susceptible S. epidermidis, and methicillin-resistant S. epidermidis with sensitivities of 95%, 80%, and 96%, respectively, and 100% specificity. The BC-GP correctly identified 14/15 cases of Enterococcus faecalis and Enterococcus faecium bacteremia and 9 cases of Streptococcus pneumoniae. It misidentified 5/15 clinical blood cultures with Streptococcus mitis/Streptococcus oralis and 1/3 blood cultures spiked with Streptococcus anginosus group as S. pneumoniae. The BC-GP detected a case of Streptococcus pyogenes bacteremia but failed to detect 2/3 clinical blood cultures with Streptococcus agalactiae. BC-GPs rapid accurate detection of Staphylococcus spp., E. faecium, and E. faecalis and its ability to ascertain mecA, vanA, and vanB status may expedite clinical decisions pertaining to optimal antibiotic use. False-positive S. pneumoniae results may warrant reporting of only “Streptococcus spp.” when this organism is reported by the BC-GP.

Pediatric Multicenter Evaluation of the Verigene Gram-Negative Blood Culture Test for Rapid Detection of Inpatient Bacteremia Involving Gram-Negative Organisms, Extended-Spectrum Beta-Lactamases, and Carbapenemases

ABSTRACT We evaluated the investigational use only (IUO) version of the rapid Verigene Gram-negative blood culture test (BC-GN), a microarray that detects 9 genus/species targets (Acinetobacter spp., Citrobacter spp., Enterobacter spp., Escherichia coli/Shigella spp., Klebsiella oxytoca, Klebsiella pneumoniae, Proteus spp., Pseudomonas aeruginosa, and Serratia marcescens) and 6 antimicrobial resistance determinants (bla CTX-M, bla KPC, bla NDM, bla VIM, bla IMP, and bla OXA) directly from positive blood cultures. BC-GN was performed on positive BacT/Alert Pediatric FAN and Bactec Peds Plus blood cultures with Gram-negative organisms at two tertiary pediatric centers. Vitek MS (bioMérieux, Durham, NC) was used to assign gold standard organism identification. The Check MDR CT-102 microarray (Check Points B.V., Wageningen, Netherlands) was used as an alternative method for detecting resistance determinants. In total, 104 organisms were isolated from 97 clinical blood cultures. BC-GN correctly detected 26/26 cultures with Acinetobacter spp., P. aeruginosa, and S. marcescens, 5/6 with Citrobacter spp., 13/14 with Enterobacter spp., 23/24 with E. coli, 2/3 with K. oxytoca, 16/17 with K. pneumoniae, and 0/1 with Proteus spp. BC-GN appropriately reported negative BC-GN results in 8/13 blood cultures that grew organisms that were not represented on the microarray but failed to detect targets in 3/5 cultures that grew multiple Gram-negative organisms. BC-GN detected 5/5 and 1/1 clinical blood cultures with bla CTX-M and bla VIM. All 6 results were corroborated by Check MDR CT-102 microarray testing. The Verigene BC-GN test has the potential to expedite therapeutic decision making in pediatric patients with Gram-negative bacteremia. Sensitivity was satisfactory but may be suboptimal in mixed Gram-negative blood cultures.

Superior Sensitivity and Decreased Time to Detection with the Bactec Peds Plus/F System Compared to the BacT/Alert Pediatric FAN Blood Culture System

ABSTRACT Here, we compare the sensitivities and times to detection (TTD) of BacT/Alert Pediatric FAN (PF) and Bactec Peds Plus blood culture bottles. Test bottles were inoculated with 2 ml of banked whole blood, 1-ml aliquots of antibiotic suspension, and organisms diluted to simulate a bacteremia level of 10 to 100 CFU/ml. The control bottles were inoculated with 3 ml of banked blood and organism suspensions only. The organism-drug combinations were Staphylococcus epidermidis and vancomycin, methicillin-resistant Staphylococcus aureus and vancomycin, Streptococcus pneumoniae, vancomycin, and ceftriaxone, Streptococcus agalactiae, ampicillin, and cefotaxime, Escherichia coli, cefotaxime, and cefepime, Pseudomonas aeruginosa, piperacillin-tazobactam, cefepime, and gentamicin, Neisseria meningitidis and ceftriaxone, and Haemophilus influenzae and ceftriaxone. The control and test bottle combinations were tested in duplicate. The bottles were incubated for 5 days; 32 control and 104 test bottles were incubated. Overall, the bacterial recovery rates for the PF and Peds Plus bottles were 37% and 62%, 94% and 100% in the controls, 19% and 50% in the test bottles, and 33% and 92% in the bottles with vancomycin, respectively. No bacteria were recovered from the bottles with S. pneumoniae, S. agalactiae, E. coli, N. meningitidis, or H. influenzae in combination with cefotaxime or ceftriaxone. The Peds Plus system detected P. aeruginosa in bottles with cefepime and piperacillin-tazobactam, but the PF system recovered bacteria only in bottles with trough levels of piperacillin-tazobactam. The mean TTD were shorter in the Peds Plus system controls (14.2 versus 18.0 h; P = 0.001) and the test bottles (14.3 versus 17.8 h; P = 0.008) than in the PF bottles. Overall, we demonstrated superior sensitivity, TTD, and antibiotic neutralization in the Bactec Peds Plus system compared to those in the Pediatric FAN system.

Bloodstream Infections in Hospitalized Children: Epidemiology and Antimicrobial Susceptibilities.

Background: Bloodstream infection is a major cause of morbidity and mortality. Much of our understanding of the epidemiology and resistance patterns of bloodstream infections comes from studies of hospitalized adults. Methods: We evaluated the epidemiology and antimicrobial resistance of bloodstream infections occurring during an 11-year period in a large, tertiary care children’s hospital in the US. All positive blood cultures were identified retrospectively from clinical microbiology laboratory records. We excluded repeat positive cultures with the same organism from the same patient within 30 days and polymicrobial infections. Results: We identified 8196 unique episodes of monomicrobial bacteremia in 5508 patients. Overall, 46% were community onset, 72% were Gram-positive bacteria, 22% Gram-negative bacteria and 5% Candida spp. Coagulase negative Staphylococcus was the most common isolated organism. ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) accounted for 20% of episodes. No S. aureus isolate was resistant to vancomycin or linezolid, and no increase in vancomycin minimum inhibitory concentration among methicillin-resistant S. aureus was observed during the study period. Clinically significant increases in vancomycin-resistant Enterococcus, ceftazidime-resistant P. aeruginosa or carbapenem-resistant Enterobacteriaceae were not observed during the study period; however, rates of methicillin-resistant S. aureus increased over time (P < 0.01). Conclusions: Gram-positive and ESKAPE organisms are leading causes of bacteremia in hospitalized children. Although antimicrobial resistance patterns were favorable compared with prior reports of hospitalized adults, multicenter studies with continuous surveillance are needed to identify trends in the emergence of antimicrobial resistance in this setting.

Rapid Detection of Methicillin-Resistant Staphylococcus aureus (MRSA) and Methicillin-Susceptible Staphylococcus aureus (MSSA) Using the KeyPath MRSA/MSSA Blood Culture Test and the BacT/ALERT System in a Pediatric Population

CONTEXT Timely initiation of directed antimicrobial therapy for Staphylococcus aureus bacteremia is dependent on rapid identification of S. aureus to ascertain methicillin-susceptibility status. OBJECTIVES To investigate the performance of the rapid KeyPath (MicroPhage, Inc, Longmont, Colorado) methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) blood culture test (MMBT). DESIGN Positive BacT/ALERT Pediatric FAN (fastidious antibiotic neutralization) blood culture bottles (bioMérieux, Inc, Durham, North Carolina) were tested prospectively using MMBT and routine bacterial identification and antibiotic susceptibility testing procedures as the gold standard. The MMBT uses an S. aureus-specific bacteriophage cocktail that infects bacterial cells and replicates them, resulting in cellular lysis. Bacteriophage-specific antibodies detect the increase in bacteriophage concentration in an immunoassay device. Phage amplification, in both the presence and absence of cefoxitin, indicates the presence of MRSA. The sensitivity, specificity, positive predictive value, and negative predictive value of MMBT in detecting S. aureus, MSSA, and MRSA were calculated. RESULTS Of 188 positive blood cultures tested, 199 (63%) had Gram-positive cocci in clusters, 46 (24%) grew S. aureus (26 MSSA [57%], 20 MRSA [43%]) with the MMBT detecting 40 of 46 (87%). The sensitivity, specificity, positive predictive value, and negative predictive value among blood cultures with Gram-positive cocci in clusters were 87%, 100%, 100%, and 92% for S. aureus; 81%, 100%, 100%, and 95% for MSSA; and 95%, 100%, 100%, and 99% for MRSA. All blood cultures without growth of S. aureus tested negative by MMBT. CONCLUSIONS The MMBT detected MSSA and MRSA directly from positive BacT/ALERT PF bottles with positive predictive values of 100%, suggesting that positive results could be reported immediately, but the sensitivity of this assay limited immediate reporting of negative results.

Positive Impact of Fungal Histopathology on Immunocompromised Pediatric Patients With Histology-Proven Invasive Fungal Infection

OBJECTIVES We investigated the performance and the clinical impact of histologic examination of infected tissue in patients with suspected invasive fungal infection (IFI) at a tertiary pediatric center. METHODS Unique episodes of IFI were identified from January 1, 2001, through December 31, 2012. Surgical pathology reports, fungal culture results, and clinical data were abstracted from medical records. RESULTS Forty-seven patients with IFI were identified. Each patient had one episode of IFI. Risk factors included chemotherapy for an oncologic condition (n = 35), hematopoietic stem cell transplantation (n = 6), solid organ transplantation (n = 4), and primary immunodeficiency (n = 2). Tissue was obtained from deep subcutaneous tissue (n = 21), visceral organs (14 lungs, five livers, and one spleen), or the sinonasal cavity (n = 6). Fungal culture was ordered in 40 of the 47 episodes of IFI. Fungus grew in 27 (68%) of the 40 cultures submitted, and all isolates were concordant with histology. Medical records were available for 36 (77%) of 47 patients. Communication of histology results prompted changes in antifungal therapy 64% of the time. This included initiation of antifungal therapy in 13 patients who were not previously receiving therapy. Fifteen (42%) patients underwent surgical excision within 48 hours of histologic diagnosis. CONCLUSIONS Histology can provide rapid, accurate, and clinically actionable information to clinicians caring for children with IFI.

Blood Volume Required for Detection of Low Levels and Ultralow Levels of Organisms Responsible for Neonatal Bacteremia by Use of Bactec Peds Plus/F, Plus Aerobic/F Medium, and the BD Bactec FX System: an In Vitro Study

ABSTRACT We used an in vitro technique to investigate blood volumes required to detect bacteremia and fungemia with low concentrations of an organism. At 1 to 10 CFU/ml, Escherichia coli, Staphylococcus epidermidis, Staphylococcus aureus, Listeria monocytogenes, Candida albicans, and Candida parapsilosis isolates were detected in volumes as low as 0.5 ml. Detection of Streptococcus agalactiae and detection of bacteremia at <1 CFU/ml were unreliable.

The Molecular and Clinical Epidemiology of Extended-Spectrum Cephalosporin– and Carbapenem-Resistant Enterobacteriaceae at 4 US Pediatric Hospitals

Objective In this report, we aim to describe the epidemiology of extended-spectrum cephalosporin-resistant (ESC-R) and carbapenem-resistant (CR) Enterobacteriaceae infections in children. Methods ESC-R and CR Enterobacteriaceae isolates from normally sterile sites of patients aged <22 years from 4 freestanding pediatric medical centers were collected along with the associated clinical data. Results The overall frequencies of ESC-R and CR isolates according to hospital over the 4-year study period ranged from 0.7% to 2.8%. Rates of ESC-R or CR Escherichia coli and Klebsiella pneumoniae varied according to hospital and ranged from 0.75 to 3.41 resistant isolates per 100 isolates (P < .001 for any differences). E coli accounted for 272 (77%) of the resistant isolates; however, a higher rate of resistance was observed in K pneumoniae isolates (1.78 vs 1.27 resistant isolates per 100 same-species isolates, respectively; P = .005). One-third of the infections caused by ESC-R or CR E coli were community-associated. In contrast, infections caused by ESC-R or CR K pneumoniae were more likely than those caused by resistant E coli to be healthcare- or hospital-associated and to occur in patients with an indwelling device (P ≤ .003 for any differences, multivariable logistic regression). Nonsusceptibility to 3 common non-β-lactam agents (ciprofloxacin, gentamicin, and trimethoprim-sulfamethoxazole) occurred in 23% of the ESC-R isolates. The sequence type 131-associated fumC/fimH-type 40-30 was the most prevalent sequence type among all resistant E coli isolates (30%), and the clonal group 258-associated allele tonB79 was the most prevalent allele among all resistant K pneumoniae isolates (10%). Conclusions The epidemiology of ESC-R and CR Enterobacteriaceae varied according to hospital and species (E coli vs K pneumoniae). Both community and hospital settings should be considered in future research addressing pediatric ESC-R Enterobacteriaceae infection.

Antibiotic prophylaxis is associated with subsequent resistant infections in children with an initial extended-spectrum-cephalosporin-resistant Enterobacteriaceae infection

ABSTRACT The objective of this study was to assess the association between previous antibiotic use, particularly long-term prophylaxis, and the occurrence of subsequent resistant infections in children with index infections due to extended-spectrum-cephalosporin-resistant Enterobacteriaceae. We also investigated the concordance of the index and subsequent isolates. Extended-spectrum-cephalosporin-resistant Escherichia coli and Klebsiella spp. isolated from normally sterile sites of patients aged <22 years were collected along with associated clinical data from four freestanding pediatric centers. Subsequent isolates were categorized as concordant if the species, resistance determinants, and fumC-fimH (E. coli) or tonB (Klebsiella pneumoniae) type were identical to those of the index isolate. In total, 323 patients had 396 resistant isolates; 45 (14%) patients had ≥1 subsequent resistant infection, totaling 73 subsequent resistant isolates. The median time between the index and first subsequent infections was 123 (interquartile range, 43 to 225) days. In multivariable Cox proportional hazards analyses, patients were 2.07 times as likely to have a subsequent resistant infection (95% confidence interval, 1.11 to 3.87) if they received prophylaxis in the 30 days prior to the index infection. In 26 (58%) patients, all subsequent isolates were concordant with their index isolate, and 7 (16%) additional patients had at least 1 concordant subsequent isolate. In 12 of 17 (71%) patients with E. coli sequence type 131 (ST131)-associated type 40-30, all subsequent isolates were concordant. Subsequent extended-spectrum-cephalosporin-resistant infections are relatively frequent and are most commonly due to bacterial strains concordant with the index isolate. Further study is needed to assess the role prophylaxis plays in these resistant infections.