Influence of transition from open bay units to single room units in a neonatal intensive care unit on hospital transmission of multi-drug-resistant Enterobacterales.

BACKGROUND: It was shown previously that changing the design of a hospital neonatal intensive care unit (NICU) from open bay units (OBUs) to single room units (SRUs) was not associated with a reduction in Gram-negative multi-drug-resistant organism (MDRO) colonization rates. It was therefore hypothesized that colonization mainly occurs vertically, or through parents and healthcare workers, and not through environmental factors, and that transition to SRUs would not decrease the number of clusters of MDROs with an epidemiological link. To investigate this, core-genome multi-locus sequence typing (cgMLST) was applied on MDROs cultured from infants at the study hospital. METHODS: This retrospective cohort study included all infants carrying MDROs admitted to the NICU of a tertiary care academic hospital 2 years prior to the transition from OBUs to SRUs in May 2017, and 1.5 years after the transition (2018-2020). RESULTS: In total, 55 infants were diagnosed with MDRO carriership. Isolates were available from 49 infants for cgMLST. In the OBU period, one cluster involving four of 20 (20%) infants was identified, and in the SRU period, four clusters involving nine of 29 (31%) infants were identified. It was possible to make an epidemiological link in all four SRU MDRO clusters, but this was not possible for the OBU cluster. In the latter case, transmission from an environmental source on the ward seemed likely. CONCLUSION: After transition to SRUs, there was no decrease in the number of clusters of MDROs with an epidemiological link, suggesting that nursing infants in an NICU with an SRU design is not, in itself, protective against the acquisition of MDROs.

Impact of transition from open bay to single room design neonatal intensive care unit on multidrug-resistant organism colonization rates.

BACKGROUND: The influence of the neonatal intensive care unit (NICU) design on the acquisition of multidrug-resistant organisms (MDROs) has not been well-documented. AIM: To examine the effect of single room unit (SRU) versus open bay unit (OBU) design on the incidence of colonization with MDROs and third-generation cephalosporin-resistant bacteria (3G-CRB) in infants admitted to the NICU. METHODS: Retrospective cohort study, including all infants admitted to the NICU of a tertiary care academic hospital two years prior to and two years following the transition from OBU to SRU in May 2017. Weekly cultures of throat and rectum were collected to screen for MDRO carriership. Incidence of colonization (percentage of all infants and incidence density per 1000 patient-days) with MDROs and 3G-CRB were compared between OBU and SRU periods. FINDINGS: Incidence analysis of 1293 NICU infants, identified 3.2% MDRO carriers (2.5% OBU, 4.0% SRU, not significant), including 2.3% extended-spectrum ß-lactamase-producing Enterobacterales carriers, and 18.6% 3G-CRB carriers (17% OBU, 20% SRU, not significant). No differences were found in MDRO incidence density per 1000 patient-days between infants admitted to OBU (1.56) compared to SRU infants (2.63). CONCLUSION: Transition in NICU design from open bay to SRUs was not associated with a reduction in colonization rates with MDROs or 3G-CRB in our hospital. Further research on preventing the acquisition and spread of resistant bacteria at high-risk departments such as the NICU, as well as optimal ward design, are needed.

Management of cerebral azole-resistant Aspergillus fumigatus infection: A role for intraventricular liposomal-amphotericin B.

OBJECTIVES: In the pre-azole era, central nervous system (CNS) infections with Aspergillus had a dismal outcome. Survival improved with voriconazole but CNS infections caused by azole-resistant Aspergillus fumigatus preclude its use. Intravenous liposomal-amphotericin B (L-AmB) is the preferred treatment option for azole-resistant CNS infections but has suboptimal brain concentrations. METHODS: We describe three patients with biopsy-proven CNS aspergillosis where intraventricular L-AmB was added to systemic therapy. Two patients with azole-resistant aspergillosis and one patient with azole-susceptible CNS aspergillosis were treated with intraventricular L-AmB at a dose of 1mg weekly. RESULTS: We describe three patients successfully treated with a combination of intravenous and intraventricular L-AmB. All three patients survived but one patient developed serious headaches, most likely not related to this treatment. CONCLUSIONS: Intraventricular L-AmB may have a role in the treatment of therapy-refractory CNS aspergillosis when added to systemic therapy.

Managing invasive aspergillosis in haematological patients in the era of resistance polymerase chain reaction and increasing triazole resistance: A modelling study of different strategies.

OBJECTIVES: Triazole resistance in Aspergillus spp. is emerging and complicates prophylaxis and treatment of invasive aspergillosis (IA) worldwide. New polymerase chain reaction (PCR) tests on broncho-alveolar lavage (BAL) fluid allow for detection of triazole resistance at a genetic level, which has opened up new possibilities for targeted therapy. In the absence of clinical trials, a modelling study delivers estimates of the added value of resistance detection with PCR, and which empiric therapy would be optimal when local resistance rates are known. DESIGN: A decision-analytic modelling study was performed based on epidemiological data of IA, extended with estimated dynamics of resistance rates and treatment effectiveness. Six clinical strategies were compared that differ in use of PCR diagnostics (used vs not used) and in empiric therapeutic choice in case of unknown triazole susceptibility: voriconazole, liposomal amphotericin B (LAmB) or both. Outcome measures were proportion of correct treatment, survival and serious adverse events. RESULTS: Implementing aspergillus PCR tests was projected to result in residual treatment-susceptibility mismatches of <5% for a triazole resistance rate up to 20% (using voriconazole). Empiric LAmB outperformed voriconazole at resistance rates >5-20%, depending on PCR use and estimated survival benefits of voriconazole over LAmB. Combination therapy of voriconazole and LAmB performed best at all resistance rates, but the advantage over the other strategies should be weighed against the expected increased number of drug-related serious adverse events. The advantage of combination therapy over LAmB monotherapy became smaller at higher triazole resistance rates. CONCLUSIONS: Introduction of current aspergillus PCR tests on BAL fluid is an effective way to increase the proportion of patients that receive targeted therapy for IA. The results indicate that close monitoring of background resistance rates and adverse drug events are important to attain the potential benefits of LAmB. The choice of strategy ultimately depends on the probability of triazole resistance, the availability of PCR and individual patient characteristics.

PCR-based detection of Aspergillus fumigatus Cyp51A mutations on bronchoalveolar lavage: a multicentre validation of the AsperGenius assay® in 201 patients with haematological disease suspected for invasive aspergillosis.

OBJECTIVES: In patients with invasive aspergillosis (IA), fungal cultures are mostly negative. Consequently, azole resistance often remains undetected. The AsperGenius® multiplex real-time PCR assay identifies clinically relevant Aspergillus species and four resistance-associated mutations (RAMs; TR34/L98H/T289A/Y121F) in the Cyp51A gene. This multicentre study evaluated the diagnostic performance of this assay on bronchoalveolar lavage (BAL) fluid and correlated the presence of RAMs with azole treatment failure and mortality. METHODS: Stored BAL samples from patients with haematological diseases with suspected IA were used. BAL samples that were galactomannan/culture positive were considered positive controls for the presence of Aspergillus. Azole treatment failure and 6 week mortality were compared in patients with and without RAMs that had received ≥5 days of voriconazole monotherapy. RESULTS: Two hundred and one patients each contributed one BAL sample, of which 88 were positive controls and 113 were negative controls. The optimal cycle threshold cut-off value for the Aspergillus species PCR was <38. With this cut-off, the PCR was positive in 74/88 positive controls. The sensitivity, specificity, positive predictive value and negative predictive value were 84%, 80%, 76% and 87%, respectively. 32/74 BAL samples were culture negative. Azole treatment failure was observed in 6/8 patients with a RAM compared with 12/45 patients without RAMs (P = 0.01). Six week mortality was 2.7 times higher in patients with RAMs (50.0% versus 18.6%; P = 0.07). CONCLUSIONS: The AsperGenius® assay had a good diagnostic performance on BAL and differentiated WT from Aspergillus fumigatus with RAMs, including in culture-negative BAL samples. Most importantly, detection of RAMs was associated with azole treatment failure.

Viral loads and antiviral resistance of herpesviruses and oral ulcerations in hematopoietic stem cell transplant recipients.

Ulcerative oral mucositis and infection are frequent complications in hematopoietic stem cell transplant (HSCT) recipients. The aim of this study was to investigate the relationship between oral ulcerations and HSV-1, EBV and CMV excretion and the presence of aciclovir-resistant HSV-1 strains in HSCT recipients. This prospective observational study included 49 adult patients who underwent allogeneic HSCT. In total, 26 patients received myeloablative and 23 received non-myeloablative conditioning. Ulcerations on non-keratinized and keratinized oral mucosa were scored and oral rinsing samples were taken twice weekly. Viral loads were determined by real-time PCR. Samples from patients remaining HSV-1 positive despite antiviral treatment were studied for resistance to antivirals. Having an HSV-1 or EBV DNA-positive sample was a significant predictor for ulceration of keratinized mucosa. HSV-1 was a significant predictor for ulcerations on non-keratinized mucosa as well. Persistent HSV-1 infection occurred in 12 of 28 patients treated with antiviral medication and aciclovir-resistant HSV-1 was found in 5 persistent infections. In conclusion, HSV-1 is a predictor of ulcerations on non-keratinized as well as keratinized oral mucosa following HSCT. The role of EBV deserves further study. Persistent HSV-1 replication despite antiviral treatment is common and is due to resistance in 18% of treated patients.

Inaccuracy of routine susceptibility tests for detection of erythromycin resistance of Campylobacter jejuni and Campylobacter coli.

In The Netherlands, both an increase in and regional differences in erythromycin resistance of Campylobacter jejuni and Campylobacter coli have been reported. To determine the accuracy of routine tests for erythromycin resistance, 48 erythromycin-resistant isolates from various laboratories that participate in the Dutch surveillance of Campylobacter infections were reinvestigated. Initial susceptibility testing for erythromycin had been performed by disk diffusion in six and MIC-based methods in two laboratories. Reinvestigation was carried out using broth microdilution as a reference standard, as well as E-test and genetic resistance testing. Of 36 C. jejuni isolates reported by the initial laboratories as erythromycin-resistant, four (11%) and five (14%) were confirmed as erythromycin-resistant using broth microdilution according to CLSI and EUCAST resistance criteria, respectively. Erythromycin resistance was found in eight of 12 (67%) C. coli isolates according to both criteria. Results of E-tests were in accordance with these results in all isolates. Resistance-associated mutations in the 23S rRNA gene (A2059G and A2058T) were found in all isolates showing high-level resistance, whereas none were found in susceptible isolates. Routine determination of the erythromycin resistance of C. jejuni and C. coli shows unacceptable interlaboratory variation. In the absence of standardized protocols and interpretive criteria for disk diffusion, and while we await the development of easily applicable and reliable methods for molecular resistance testing, the use of broth microdilution remains the best method.

Mycobacterium chelonae keratitis in a patient with Sjögren's syndrome.

PURPOSE: In this report a case of Mycobacterium chelonae keratitis in a patient without any previously described risk factors is described. The only risk factor found was a rheumatoid arthritis related Sjogren''s syndrome. METHODS: Case report. RESULTS: A 60-year-old woman was referred to the hospital with an infectious keratitis of the left eye of 3 months duration, unresponsive to empirical therapy with ofloxacin and tobramycin drops. Her medical history included a longstanding rheumatoid arthritis and a secondary ocular surface syndrome. Upon arrival the left eye showed diffuse corneal edema and centrally several large infiltrates with fluffy edges, surrounded by several smaller satellite infiltrates. The cornea was scraped for culture and grew M chelonae and sensitivity testing showed sensitivity to ciprofloxacin, clofazimine, and clarithromycin. Systemically, ciprofloxacin 750 mg and clarithromycin 500 mg twice daily were prescribed orally. Topical therapy consisted of topical erythromycin 10 mg/mL and ofloxacin 3 mg/mL every 2 hours. Treatment was continued for a total of 10 months during which the infiltrates cleared completely, but the central cornea remained scarred. CONCLUSIONS: M chelonae can be a cause of infectious keratitis in patients without known risk factors for rapidly growing mycobacterium keratitis. Especially in the case of ocular infections that show no response to regular antibacterial treatment, mycobacterial infection should be considered. Good communication between the ophthalmologist and the microbiologist is crucial for a rapid diagnosis.