Review of allergic reactions from use of chlorhexidine on medical products in clinical settings over 40 years: Risks and mitigations.

Chlorhexidine is an antimicrobial agent widely used for infection prevention in medical settings. Nevertheless, allergic reactions ranging from mild to severe have been reported following its use. In this review, we analyzed all case reports published between the introduction of chlorhexidine and the end of 2019 for allergic responses associated with the use of medical devices and or other medical products containing chlorhexidine (CHX) to ascertain the prevalence of severe CHX allergic reactions and what practices might best mitigate those risks.In total, 77 publications containing 124 reported cases of allergic reactions were grouped into 3 product categories, catheters, semisolids, and fluid products. The country, type of reaction, route of sensitization, allergy confirmation, and intervention or mitigation was extracted for each case. Overall, 30 cases were associated with catheters, 46 cases were associated with semisolid products, and 48 cases were associated with the use of other medical products. Severe cases were managed with intravenous fluids, steroids, and epinephrine (adrenaline). None of the reported cases were fatal. The allergy risks can be mitigated by better warning and training clinicians and by recording and screening patient histories for CHX presensitization from prior exposure. For patients undergoing pre-use blood tests, IgE antibody screens can also be performed. Finally, as a precaution in the event a rare severe allergic reaction occurs, procedure carts and rooms can be prestocked with injectable epinephrine and other rapidly acting anti-inflammatory medications.

Drosophila melanogaster as a model to study virulence and azole treatment of the emerging pathogen Candida auris.

OBJECTIVES: Candida auris is an emerging, often MDR, yeast pathogen. Efficient animal models are needed to study its pathogenicity and treatment. Therefore, we developed a C. auris fruit fly infection model. METHODS: TollI-RXA/Tollr632 female flies were infected with 10 different C. auris strains from the CDC Antimicrobial Resistance bank panel. We used three clinical Candida albicans strains as controls. For drug protection assays, fly survival was assessed along with measurement of fungal burden (cfu/g tissue) and histopathology in C. auris-infected flies fed with fluconazole- or posaconazole-containing food. RESULTS: Despite slower in vitro growth, all 10 C. auris isolates caused significantly greater mortality than C. albicans in infected flies, with >80% of C. auris-infected flies dying by day 7 post-infection (versus 67% with C. albicans, P < 0.001-0.005). Comparison of C. auris isolates from different geographical clades revealed more rapid in vitro growth of South American isolates and greater virulence in infected flies, whereas the aggregative capacity of C. auris strains had minimal impact on their growth and pathogenicity. Survival protection and decreased fungal burden of fluconazole- or posaconazole-fed flies infected with two C. auris strains were in line with the isolates' disparate in vitro azole susceptibility. High reproducibility of survival curves for both non-treated and antifungal-treated infected flies was seen, with coefficients of variation of 0.00-0.31 for 7 day mortality. CONCLUSIONS: Toll-deficient flies could provide a fast, reliable and inexpensive model to study pathogenesis and drug activity in C. auris candidiasis.

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.

Multistate outbreak of Serratia marcescens bloodstream infections caused by contamination of prefilled heparin and isotonic sodium chloride solution syringes.

BACKGROUND: To investigate clusters of Serratia marcescens (SM) bloodstream infections (BSIs) at health care facilities in several states and determine whether contaminated prefilled heparin and isotonic sodium chloride solution (hereinafter, saline) syringes from a single manufacturer (company X) were the likely cause, we performed an outbreak investigation of inpatient and outpatient health care facilities from October 2007 through February 2008. METHODS: Active case finding for clusters of SM BSIs. Information on SM BSIs was obtained, and SM blood isolates were sent to the Centers for Disease Control and Prevention (CDC). Culture specimens were taken from various lots of prefilled heparin and saline syringes by health care facilities and the CDC to test for the presence of SM. The SM isolates from syringes and blood were compared by pulsed-field gel electrophoresis. RESULTS: A total of 162 SM BSIs in 9 states were reported among patients at facilities using prefilled heparin and/or saline syringes made by company X. Cultures of unopened prefilled heparin and saline syringes manufactured by company X grew SM. Of 83 SM blood isolates submitted to the CDC from 7 states, 70 (84%) were genetically related to the SM strain isolated from prefilled syringes. A US Food and Drug Administration inspection revealed that company X was not in compliance with quality system regulations. CONCLUSIONS: A multistate outbreak of SM BSIs was associated with intrinsic contamination of prefilled syringes. Our investigation highlights important issues in medication safety, including (1) the importance of pursuing possible product-associated outbreaks suggested by strong epidemiologic data even when initial cultures of the suspected product show no contamination and (2) the challenges of medical product recalls when production has been outsourced from one company to another.

Multidrug-resistant Escherichia coli bacteremia in cancer patients.

BACKGROUND: Multidrug-resistant (MDR) Escherichia coli is a serious threat to cancer patients. We aimed to determine the risk factors associated with the development of MDR E coli bacteremia in cancer patients and the possibility of horizontal transmission. METHODS: We conducted a 1:2 case-control study of 58 patients with MDR E coli bacteremia. The patient's demographics, clinical characteristics, and antibiotic use were obtained. MDR E coli was defined as resistant strains to quinolones plus 1 of the following: piperacillin, ceftazidime, or cefepime. Repetitive sequence-based polymerase chain reaction (Rep-PCR) was used to identify DNA interstrain similarities. RESULTS: Conditional multiple logistic analysis showed that admission to the hospital within the 30 days prior to infection and chemotherapy use were risk factors for infection with MDR E coli. Rep-PCR showed that, among the MDR E coli strains recovered, 48.6% showed >95% similarity, representing a possible clonal outbreak. Infection control measures were implemented and controlled this horizontal transmission. CONCLUSION: Prior admission to the hospital and previous chemotherapy were independent risk factors of acquiring MDR E coli. Molecular fingerprinting techniques detected a possible nosocomial clonal outbreak of MDR E coli, which was aborted through infection control measures.

Extrapulmonary tuberculosis active infection misdiagnosed as cancer: Mycobacterium tuberculosis disease in patients at a Comprehensive Cancer Center (2001-2005).

BACKGROUND: Extrapulmonary tuberculosis is an uncommon disease in the U.S., even in immunosuppressed cancer patients. This study evaluated characteristics and frequency of extrapulmonary tuberculosis in patients at a tertiary care referral cancer center. METHODS: The records of all consecutive patients with Mycobacterium tuberculosis diagnosed during January 2001 through April 2005 at the M. D. Anderson Cancer Center were reviewed after obtaining institutional review board approval. RESULTS: There were 26 patients with active tuberculosis during the period studied; 18 of them were cancer patients and the others had been referred for a presumed cancer but did not have cancer. The overall rate of active tuberculosis during this period was 0.2 in 1000 new cancer diagnoses. There were 18 men (69%), the median age was 54 years (range, 3-84 yrs), and 16 patients (62%) were born in the U.S. Thirteen (72%) of the 18 cancer patients had solid-organ tumors; 3 of the 5 patients with a hematologic malignancy had non-Hodgkin lymphoma. Three patients (12%) had diabetes mellitus, and 2 patients (8%) had received high-dose (>1 mg/kg of prednisone daily) corticosteroids in the previous week. No patient had a recent history (within the past 4 wks) of chemotherapy; 4 patients had neutropenia. Cough was a prominent symptom (31%), followed by bone pain (19%), dyspnea (15%), and fever (12%). Fifteen patients (58%) had extrapulmonary infection, including 5 patients with concurrent pulmonary involvement; 7 noncancer patients (88%) and 8 cancer patients (44%, P = 0.22) had extrapulmonary disease. In 11 patients (42%), the lungs were the only site of active tuberculosis. Cavitary pneumonia was seen radiographically in 3 of 16 patients (19%) with pulmonary tuberculosis. All M. tuberculosis isolates were susceptible to isoniazid, rifampin, ethambutol, and pyrazinamide; streptomycin resistance was noted in 1 of 22 (5%) isolates tested. Twenty-two patients (85%) received appropriate antituberculosis treatment; all had a clinical and radiographic response. In 3 patients (12%) the cause of death was attributed to M. tuberculosis disease; 2 of 18 cancer patients (11%) died of progressive M. tuberculosis, and they had advanced solid-organ cancer, whereas 1 of 8 patients (13%) without cancer died and the tuberculosis diagnosis was made only on postmortem examination. Univariate analysis showed no significant differences in patients or disease characteristics between non-U.S.-born and U.S.-born patients, whereas noncancer patients (age 52 yrs) and those with extrapulmonary tuberculosis (age 53 yrs) were younger compared with cancer patients (63 yrs; P < 0.007) and those with pulmonary disease (age 60 yrs; P = 0.09). CONCLUSIONS: Extrapulmonary tuberculosis was relatively common in younger patients with active M. tuberculosis infection, and was often initially misdiagnosed as cancer.

Invasive aspergillosis in patients with solid tumors.

Invasive aspergillosis (IA) has been reported only rarely among patients with solid tumors. In the current study, the authors retrospectively identified 13 episodes of definite or probable IA (using European Organization for Research and Treatment of Cancer criteria) occurring in patients with solid tumors who were treated between 1994-2003. Nine patients had pulmonary IA and three patients were found to have IA of the brain. Seven patients (54%) had primary or metastatic brain tumors and 6 patients (46%) received systemic steroids within 30 days prior to the diagnosis of IA. The majority of patients (69%) had a lymphocyte count < 500/microL but only 1 patient was neutropenic within the 30 days before the diagnosis of IA was made. Nodular infiltrates and cavities were the most common radiologic findings. Seven patients (54%) responded to antifungal treatment.

Amphotericin B lipid complex as prophylaxis of invasive fungal infections in patients with acute myelogenous leukemia and myelodysplastic syndrome undergoing induction chemotherapy.

BACKGROUND: The optimal antifungal prophylactic regimen for patients with acute myelogenous leukemia (AML) or high-risk myelodysplastic syndrome (MDS) undergoing induction chemotherapy has yet to be identified. A prospective historical control study evaluated the efficacy and safety of amphotericin B lipid complex (ABLC) in this patient population. METHODS: Newly diagnosed patients with AML or high-risk MDS who were undergoing induction chemotherapy received prophylactic ABLC 2.5 mg/kg intravenously 3 times weekly. This treatment group was compared with a historical control group that had similar baseline characteristics and received prophylactic liposomal amphotericin B (L-AmB) 3 mg/kg 3 times weekly. The primary endpoint was the incidence of documented or suspected fungal infections during and up to 4 weeks after cessation of prophylaxis. Reported adverse events were used to assess tolerability. RESULTS: The overall efficacy of antifungal prophylaxis was similar in patients who received ABLC and patients who received L-AmB (P=0.95). Among 131 ABLC-treated patients and 70 L-AmB-treated patients who were assessed for efficacy and safety, 49% of patients in each group completed therapy without developing a documented or suspected fungal infection. Documented fungal infections occurred in 5% of ABLC-treated patients and in 4% of L-AmB-treated patients. Alternative antifungal strategies were required because of persistent fever or pneumonia of unknown pathogen in 28% and 32% of ABLC-treated and L-AmB-treated patients, respectively. Grade 3 and 4 adverse events, therapy discontinuations due to adverse events, and survival rates also were similar between treatment groups. CONCLUSIONS: ABLC and L-AmB appeared to have similar efficacy and were tolerated well as antifungal prophylaxis in patients with AML and high-risk MDS who were undergoing induction chemotherapy.