Micah M. Bhatti

Clinical Features of Candidiasis in Patients With Inherited Interleukin 12 Receptor β1 Deficiency

BACKGROUND Interleukin 12Rβ1 (IL-12Rβ1)-deficient patients are prone to clinical disease caused by mycobacteria, Salmonella, and other intramacrophagic pathogens, probably because of impaired interleukin 12-dependent interferon γ production. About 25% of patients also display mucocutaneous candidiasis, probably owing to impaired interleukin 23-dependent interleukin 17 immunity. The clinical features and outcome of candidiasis in these patients have not been described before, to our knowledge. We report here the clinical signs of candidiasis in 35 patients with IL-12Rβ1 deficiency. RESULTS Most (n = 71) of the 76 episodes of candidiasis were mucocutaneous. Isolated oropharyngeal candidiasis (OPC) was the most common presentation (59 episodes, 34 patients) and was recurrent or persistent in 26 patients. Esophageal candidiasis (n = 7) was associated with proven OPC in 2 episodes, and cutaneous candidiasis (n = 2) with OPC in 1 patient, whereas isolated vulvovaginal candidiasis (VVC; n = 3) was not. Five episodes of proven invasive candidiasis were documented in 4 patients; 1 of these episodes was community acquired in the absence of any other comorbid condition. The first episode of candidiasis occurred earlier in life (median age±standard deviation, 1.5 ± 7.87 years) than infections with environmental mycobacteria (4.29 ± 11.9 years), Mycobacterium tuberculosis (4 ± 3.12 years), or Salmonella species (4.58 ± 4.17 years) or other rare infections (3 ± 11.67 years). Candidiasis was the first documented infection in 19 of the 35 patients, despite the vaccination of 10 of these 19 patients with live bacille Calmette-Guérin. CONCLUSIONS Patients who are deficient in IL-12Rβ1 may have candidiasis, usually mucocutaneous, which is frequently recurrent or persistent. Candidiasis may be the first clinical manifestation in these patients.

High Rates of Nonsusceptibility to Ceftazidime-avibactam and Identification of New Delhi Metallo-β-lactamase Production in Enterobacteriaceae Bloodstream Infections at a Major Cancer Center

Resistance to the novel β-lactam/β-lactamase inhibitor combination ceftazidime-avibactam (CAZ-AVI) among carbapenem-resistant Enterobacteriaceae (CRE) has infrequently been reported in the United States. We report unexpectedly high rates of resistance to CAZ-AVI in CRE bloodstream isolates at our institution associated with the nonoutbreak spread of New Delhi metallo-β-lactamase in diverse Enterobacteriaceae species.

Severe influenza in 33 US hospitals, 2013–2014: Complications and risk factors for death in 507 patients

BACKGROUND Influenza A (H1N1) pdm09 became the predominant circulating strain in the United States during the 2013-2014 influenza season. Little is known about the epidemiology of severe influenza during this season. METHODS A retrospective cohort study of severely ill patients with influenza infection in intensive care units in 33 US hospitals from September 1, 2013, through April 1, 2014, was conducted to determine risk factors for mortality present on intensive care unit admission and to describe patient characteristics, spectrum of disease, management, and outcomes. RESULTS A total of 444 adults and 63 children were admitted to an intensive care unit in a study hospital; 93 adults (20.9%) and 4 children (6.3%) died. By logistic regression analysis, the following factors were significantly associated with mortality among adult patients: older age (>65 years, odds ratio, 3.1 [95% CI, 1.4-6.9], P=.006 and 50-64 years, 2.5 [1.3-4.9], P=.007; reference age 18-49 years), male sex (1.9 [1.1-3.3], P=.031), history of malignant tumor with chemotherapy administered within the prior 6 months (12.1 [3.9-37.0], P<.001), and a higher Sequential Organ Failure Assessment score (for each increase by 1 in score, 1.3 [1.2-1.4], P<.001). CONCLUSION Risk factors for death among US patients with severe influenza during the 2013-2014 season, when influenza A (H1N1) pdm09 was the predominant circulating strain type, shifted in the first postpandemic season in which it predominated toward those of a more typical epidemic influenza season.

Bacterial and viral co-infections complicating severe influenza: Incidence and impact among 507 U.S. patients, 2013–14

Abstract Background Influenza acts synergistically with bacterial co-pathogens. Few studies have described co-infection in a large cohort with severe influenza infection. Objectives To describe the spectrum and clinical impact of co-infections. Study design Retrospective cohort study of patients with severe influenza infection from September 2013 through April 2014 in intensive care units at 33 U.S. hospitals comparing characteristics of cases with and without co-infection in bivariable and multivariable analysis. Results Of 507 adult and pediatric patients, 114 (22.5%) developed bacterial co-infection and 23 (4.5%) developed viral co-infection. Staphylococcus aureus was the most common cause of co-infection, isolated in 47 (9.3%) patients. Characteristics independently associated with the development of bacterial co-infection of adult patients in a logistic regression model included the absence of cardiovascular disease (OR 0.41 [0.23–0.73], p=0.003), leukocytosis (>11K/μl, OR 3.7 [2.2–6.2], p<0.001; reference: normal WBC 3.5–11K/μl) at ICU admission and a higher ICU admission SOFA score (for each increase by 1 in SOFA score, OR 1.1 [1.0–1.2], p=0.001). Bacterial co-infections (OR 2.2 [1.4–3.6], p=0.001) and viral co-infections (OR 3.1 [1.3–7.4], p=0.010) were both associated with death in bivariable analysis. Patients with a bacterial co-infection had a longer hospital stay, a longer ICU stay and were likely to have had a greater delay in the initiation of antiviral administration than patients without co-infection (p<0.05) in bivariable analysis. Conclusions Bacterial co-infections were common, resulted in delay of antiviral therapy and were associated with increased resource allocation and higher mortality.

Use of ceftolozane/tazobactam in the treatment of multidrug-resistant pseudomonas aeruginosa bloodstream infection in a pediatric leukemia patient

Multidrug-resistant Pseudomonas aeruginosa is of increasing concern in pediatric patients. Ceftolozane/tazobactam is a novel cephalosporin/β-lactamase inhibitor combination with activity against multidrug-resistant Pseudomonas; however, no data exist on its use in children. This report summarizes the treatment of a multidrug-resistant P. aeruginosa bloodstream infection in a pediatric leukemia patient with ceftolozane/tazobactam and provides the first description of its pharmacokinetics in pediatrics.

Eight-Year Review of Bordetella pertussis Testing Reveals Seasonal Pattern in the United States

Review of Bordetella pertussis polymerase chain reaction testing from 2007 through 2014 revealed a yearly spike in positivity rates during the summer throughout the United States. Paradoxically, the highest test volumes occurred outside of this time frame, which provides an opportunity for improved test utilization.

Clonal Emergence of Invasive Multidrug-Resistant Staphylococcus epidermidis Deconvoluted via a Combination of Whole-Genome Sequencing and Microbiome Analyses

Background Pathobionts, bacteria that are typically human commensals but can cause disease, contribute significantly to antimicrobial resistance. Staphylococcus epidermidis is a prototypical pathobiont as it is a ubiquitous human commensal but also a leading cause of healthcare-associated bacteremia. We sought to determine the etiology of a recent increase in invasive S. epidermidis isolates resistant to linezolid. Methods Whole-genome sequencing (WGS) was performed on 176 S. epidermidis bloodstream isolates collected at the MD Anderson Cancer Center in Houston, Texas, between 2013 and 2016. Molecular relationships were assessed via complementary phylogenomic approaches. Abundance of the linezolid resistance determinant cfr was determined in stool samples via reverse-transcription quantitative polymerase chain reaction. Results Thirty-nine of the 176 strains were linezolid resistant (22%). Thirty-one of the 39 linezolid-resistant S. epidermidis infections were caused by a particular clone resistant to multiple antimicrobials that spread among leukemia patients and carried cfr on a 49-kb plasmid (herein called pMB151a). The 6 kb of pMB151a surrounding the cfr gene was nearly 100% identical to a cfr-containing plasmid isolated from livestock-associated staphylococci in China. Analysis of serial stool samples from leukemia patients revealed progressive staphylococcal domination of the intestinal microflora and an increase in cfr abundance following linezolid use. Conclusions The combination of linezolid use plus transmission of a multidrug-resistant clone drove expansion of invasive, linezolid-resistant S. epidermidis. Our results lend support to the notion that a combination of antibiotic stewardship plus infection control measures may help to control the spread of a multidrug-resistant pathobiont.

Graft loss attributed to possible transfusion-transmitted ehrlichiosis following cord blood stem cell transplant

We present a case of possible transfusion‐transmitted Ehrlichia chaffeensis infection in a heavily transfused cord blood transplant recipient, resulting in severe infection and graft loss. Transfusion‐transmitted, vector‐borne infections in immunocompromised individuals can have severe consequences, and should be considered in hospitalized patients receiving blood products with unexplained fever or sepsis.

Line of Service-Specific Performance and Antibiotic Prescribing Habits Following Introduction of a Two-Step Diagnostic Approach Using NAAT Followed by Enzyme Immunoassay in Cancer Patients with Suspected Clostridium difficile Infection

Abstract Background Patients with cancer are at an increased risk for C. difficile infection (CDI). A two-step approach with a Nucleic Acid Amplification Test (NAAT) followed by enzyme immunoassay (EIA) increases diagnostic sensitivity and specificity and can be used to guide antibiotic therapy. We retrospectively investigated the relative performance of the two-step approach in cancer patients with solid tumors (ST), hematologic malignancies (HS), and hematopoietic stem cell transplant recipients (HSCT). Methods We identified 204 patients with a positive NAAT test for CDI as determined by GI multiplex (Biofire) or by Illumigene (Meridian, Bioscience) in whom a reflex EIA was performed for C. difficile A/B toxins between November 2015 and February 2017. Patients were stratified into ST, HM, HSCT groups. We compared the proportion of discordant NAAT+, EIA- results among the three groups. We then compared the clinical presentation and antibiotic use for patients in the NAAT+/EIA- to those with NAAT+/EIA+ results. Results Overall an EIA+ result was found in 53 (26%) patients. The proportion of patients with NAAT+/EIA+ results was significantly different between the three lines of service; ST 31/86 (36%), HM 16/62 (26%), and HSCT 6/56 (11%) P < 0.01. A trend towards a higher proportion of positive results was observed for ST compared with the HM group (P = 0.06). Results were similar between the HM and HSCT group. However, patients in the ST were more likely to have a positive EIA when compared with HSCT patients (36% vs. 11% P < 0.01). Clinical presentation and healthcare-association were similar in all three groups regardless of the EIA result. Despite the low proportion of EIA+ confirmatory results, the majority of patients (196/204 96%) received antibiotic therapy targeting CDI. Discontinuation of CDI antibiotics prior to 10 days of therapy was similar in the EIA+ (12%) vs. EIA- (10%). Conclusion The relevance of discordant results needs to be interpreted in the context of the line of service/patient care unit. The presence of CDI as determined by NAAT/EIA is low in patients with other potential causes of diarrhea such as in HSCT recipients. A substantial proportion of cancer patients are treated unnecessarily for CDI. Disclosures All authors: No reported disclosures.

Ribotypes matter, significance of Clostridium difficile ribotypes in cancer patients with diarrhea.

Abstract Background Cancer patients are at increased risk for Clostridium difficile infection (CDI) due to frequent health care contact, chemotherapy, use of antibiotics, and immunosuppression. Distinct ribotypes are associated with CDI adverse outcomes. Ribotypes 14-020 are the predominant ribotypes in many hospitals. We examined the contribution of C. difficile ribotypes to CDI severity, response to therapy and outcomes in this population. Methods Demographic and clinical data were collected from 90 cancer patients with a first episode or first recurrence of CDI identified by two-step PCR followed by EIA for A/B toxins. Fluorescent PCR ribotyping (FPCR) was performed on fecal isolates. We identified 27 distinct ribotypes between October 2016 and January 2017. Clinical outcomes were studied in three FPCR subgroups. Group I (GI, n = 27) included F014-020, group II (GII, n = 17) included virulent types 002, 027, 078–126, 244 and group III (GIII, n = 46) included the rest. Treatment failure was defined as no response after at least 3 days of a CDI treatment regimen. CDI severity was determined using Zar’s criteria, presence of bacteremia and ICU stay. Results The proportion of patients >50 yrs. old, with health care onset CDI (31%), primary CDI (92.2%), and on active chemotherapy (70%) was similar across the three groups. At presentation, disease severity was similar in all groups; However, patients in GII were more likely to have detectable toxin A/B by EIA compared with GI and GIII (53% vs. 23%, P = 0.015) and higher treatment failure rates (56%) when compared with GI (15% P = 0.007) and GIII (16%, P = 0.004). Bacteremia was more common in GIII (28%) compared with GII (0%) P = 0.041 and GI 7% P = 0.007. Patients in GI experienced fewer complications when compared with those in GIII P = 0.025. No differences in sustained clinical response, recurrence, ICU stay or all cause 90-day mortality were found between the groups. Conclusion Cancer patients with CDI due to GII ribotypes are more likely to excrete fecal toxin A/B and fail conventional therapy. In contrast, patients in GI and GIII were more likely to respond to therapy. GI was associated with fewer complications. Of interest, GIII was associated with bacteremia. Evaluation of C. difficile ribotypes is clinically relevant in cancer patients with CDI. Disclosures All authors: No reported disclosures.