Increase of healthcare-onset Clostridioides difficile infection in adult population since SARS-CoV-2 pandemic: A retrospective cohort study in a tertiary care hospital from 2019 to 2022.

OBJECTIVES: The aim was to assess the impact of the SARS-CoV-2 pandemic on the prevalence, relative incidence (RI), incidence density (ID), ratio of rate incidence (RRI), rate of incidence density (RID), and relative risks (RR) of healthcare-onset Clostridioides difficile infection (HO-CDI) as well as its correlation with the antibiotic consumption. METHODS: Demographic and analytical data of adult patients exhibiting diarrhoea and testing positive for C. difficile were systematically collected from a tertiary care hospital in Madrid (Spain). The periods analysed included: prepandemic (P0), first pandemic-year (P1), and second pandemic-year (P2). We compared global prevalence, RI of HO-CDI per 1,000-admissions, ID of HO-CDI per 10,000-patients-days, RRI, RID, and RR. Antibiotic consumption was obtained by number of defined daily dose per 100 patient-days. RESULTS: In P0, the prevalence of HO-CDI was 7.4% (IC95%: 6.2-8.7); in P1, it increased to 8.7% (IC95%: 7.4-10.1) (p = 0.2), and in P2, it continued to increase to 9.2% (IC95%: 8-10.6) (p < 0.05). During P1, the RRI was 1.5 and RID was 1.4. However, during P2 there was an increase in RRI to 1.6 and RID to 1.6. The RR also reflected the increase in HO-CDI: at P1, the probability of developing HO-CDI was 1.5 times (IC95%: 1.2-1.9) higher than P0, while at P2, this probability increased to 1.6 times (IC95%: 1.3-2.1). There was an increase in prevalence, RI, ID, RR, RRI, and RID during the two postpandemic periods respect to the prepandemic period. During P2, this increase was greater than the P1. Meropenem showed a statistically significant difference increased consumption (p < 0.05) during the pandemic period. Oral vancomycin HO-CDI treatment showed an increase during the period of study (p > 0.05). CONCLUSIONS: Implementation of infection control measures during the SARS-CoV-2 pandemic did not appear to alleviate the burden of HO-CDI. The escalation in HO-CDI cases did not exhibit a correlation with overall antibiotic consumption, except for meropenem.

Bezlotoxumab during the first episode of Clostridioides difficile infection in patients at high risk of recurrence.

PURPOSE: To describe a cohort with a high risk of recurrence who received bezlotoxumab during the first episode of Clostridioides difficile infection (CDI) and to compare this cohort with patients with similar characteristics who did not receive the monoclonal antibody. METHODS: A prospective and multicentre study of patients with a high risk of recurrence (expected recurrence rate>35%) who were treated with bezlotoxumab during their first episode of CDI was conducted. A propensity score-matched model 1:2 was used to compare both cohorts that were weighed according to basal characteristics (hospital-acquisition, creatinine value, and fidaxomicin as a CDI treatment). RESULTS: Sixty patients (mean age:72 years) were prospectively treated with bezlotoxumab plus anti-Clostridioides antibiotic therapy. Vancomycin (48 patients) and fidaxomicin (12 patients) were prescribed for CDI treatment, and bezlotoxumab was administered at a mean of 4.2 (SD:2.1) days from the beginning of therapy. Recurrence occurred in nine out of 54 (16.7%) evaluable patients at 8 weeks. Forty bezlotoxumab-treated patients were matched with 69 non-bezlotoxumab-treated patients. Recurrence rates at 12 weeks were 15.0% (6/40) in bezlotoxumab-treated patients vs. 23.2% (16/69) in non-bezlotoxumab-treated patients (OR:0.58 [0.20-1.65]). No adverse effects were observed related to bezlotoxumab infusion. Only one of 9 patients with previous heart failure developed heart failure. CONCLUSION: We observed that patients treated with bezlotoxumab in a real-world setting during a first episode of CDI having high risk of recurrence, presented low rate of recurrence. However, a significant difference in recurrence could not be proved in comparison to the controls. We did not detect any other safety concerns.

Impact on tuberculosis diagnostic during COVID-19 pandemic in a tertiary care hospital.

INTRODUCTION: The aim of this study is to review how did the first three COVID-19 waves affected the diagnostic of tuberculosis and to describe the extra-pulmonary Mycobacterium tuberculosis complex (TB) diagnosis. MATERIALS AND METHODS: A retrospective observational study was done during the first three waves of pandemic to ascertain the impact on TB samples and to recover the extra-pulmonary TB cases we included the first two years of COVID-19. All relevant data was recovered from hospital and Clinical Microbiology records. RESULTS: Prepandemic period showed an average of 44 samples per week for TB study; during the first three waves this number dropped to 23.1 per week. A reduction of 67.7% of pulmonary TB diagnosis was observed and an increase of 33.3% diagnosis of extra-pulmonary TB was noted when comparing pre-pandemic and pandemic period. DISCUSSION: The number of declared cases and samples for TB diagnosis dropped during the first three COVID-19 waves due to the overstretched Public Health System which could lead to a delay in diagnosis, treatment and to the spread of TB disease in the general population. Surveillance programs should be reinforced to avoid this.

A Comparison of the Efficacy of Treatment With Fidaxomicin Versus Vancomycin in Clostridioides difficile Infection.

Background Clostridioides difficile infection (CDI) is a major cause of diarrhea in hospitalized adult patients. This study aims to evaluate the clinical characteristics, clinical cure, recurrence and mortality in patients with CDI treated with either fidaxomicin or vancomycin. Methods A retrospective case-control study was conducted on patients with CDI treated with either fidaxomicin or vancomycin at a hospital from January 2019 to March 2022. Results We assessed 140 patients with CDI episodes, 70 patients treated with fidaxomicin and 70 with vancomycin. Seventy (50%) were male. Median age was 70 years old (IQR: 56-81). Fidaxomicin group had more recurrent CDI episodes within six months (59% vs 11%, p ≤ 0.001), more severity (43% vs 16%, p ≤ 0.001) and less treatment response (84% vs 100%, p ≤ 0.002) compared with vancomycin group. Recurrence and mortality rates in the follow-up period did not differ in both groups. Conclusions Our study found fidaxomicin treatment had worse outcomes due to restricted usage, potentially impacting its effectiveness in CDI. This finding is especially significant for patients with severe or recurrent CDI, as prescribing of the drug was limited until May 2022 in Spain with the lifting of this restriction, further research is necessary to better understand the potential benefits of fidaxomicin in treating CDI.

Evaluation of the effectiveness and safety of oral vancomycin versus placebo in the prevention of recurrence of Clostridioides difficile infection in patients under systemic antibiotic therapy: a phase III, randomised, double-blind clinical trial.

INTRODUCTION: Clostridioides difficile infection (CDI) is the most prevalent cause of nosocomial bacterial diarrhoea and it is strongly associated with antibiotic use. The recurrence of CDI is a growing medical problem. Data from real-life studies and one open label randomised clinical trial (RCT) suggest that secondary prophylaxis with oral vancomycin (SPV) during subsequent courses of systemic antibiotics is a promising approach for reducing the risk of CDI recurrence. Our aim is to confirm the role of SPV through a double-blind RCT. METHODS AND ANALYSIS: We will perform a phase III, multicentre, placebo-controlled RCT (PREVAN trial) in a 2:1 ratio in favour of SPV (experimental treatment), in four tertiary care hospitals in Spain. Adult patients (≥18 years) with a previous history of CDI in the previous 180 days and with requirement for hospitalisation and systemic antibiotic therapy will be randomly allocated to receive either 125 mg of oral vancomycin or placebo every 6 hours for 10 days. Patients will be followed for 60 days after the end of treatment to verify a reduction in the rate of CDI recurrence in the experimental group. We assume a recurrence rate of 5% in the experimental group versus 25% in the placebo group. Accepting an alpha risk of 0.05 and a beta risk of 0.2 in a two-sided test, 104 subjects will be required in total (68 assigned to the SPV group and 34 to the placebo group). ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Ethic Committee for Research with medicinal products of the University Hospital '12 de Octubre' (AC069/18) and from the Spanish Medicines and Healthcare Product Regulatory Agency (AEMPS, AC069/18), which is valid for all participating centres under existing Spanish legislation. The results will be presented at international meetings and will be made available to patients and funders. TRIAL REGISTRATION NUMBER: NCT05320068.

[IMPACT ON TUBERCULOSIS DIAGNOSTIC DURING COVID-19 PANDEMIC IN A TERTIARY CARE HOSPITAL]. / IMPACTO DE LA PANDEMIA COVID-19 EN EL DIAGNOSTICO DE TUBERCULOSIS EN UN HOSPITAL DE TERCER NIVEL.

INTRODUCTION: The aim of this study is to review how did the first three COVID-19 waves affected the diagnostic of tuberculosis and to describe the extra-pulmonary Mycobacterium tuberculosis complex (TB) diagnosis. MATERIALS AND METHODS: A retrospective observational study was done during the first three waves of pandemic to ascertain the impact on TB samples and to recover the extra-pulmonary TB cases we included the first two years of COVID-19. All relevant data was recovered from hospital and Clinical Microbiology records. RESULTS: Prepandemic period showed an average of 44 samples per week for TB study; during the first three waves this number dropped to 23.1 per week. A reduction of 67.7% of pulmonary TB diagnosis was observed and an increase of 33.3% diagnosis of extra-pulmonary TB was noted when comparing pre-pandemic and pandemic period. DISCUSSION: The number of declared cases and samples for TB diagnosis dropped during the first three COVID-19 waves due to the overstretched Public Health System which could lead to a delay in diagnosis, treatment and to the spread of TB disease in the general population. Surveillance programs should be reinforced to avoid this.

Clinical Cure of a Difficult-to-Treat Resistant Pseudomonas aeruginosa Ventriculitis Using Cefiderocol: A Case Report and Literature Review.

Ventriculitis is a complication of meningitis (community-acquired or nosocomial) or other central nervous system (CNS) infections such as brain abscess. They are associated with a different spectrum of microorganisms, from resistant gram-negative bacilli to staphylococci, that can lead serious illness with high mortality. Difficult-to-treat resistance (DTR) gram-negative bacilli may increase to 20% of deaths respective to susceptible isolates of the same bacteria. We present the first report of a clinical cured case of DTR Pseudomonas aeruginosa ventriculitis in which cefiderocol penetration into the CNS has been confirmed in blood and cerebrospinal fluid. Cefiderocol might be considered for difficult-to-treat CNS infections in view of the recent new cases published as well as our case.

Urinary Tract Infections in Hospitalized COVID-19 Patients, What's Up, Doc?

The SARS-CoV-2 pandemic might have increased the risks of healthcare-associated infections (HAIs); however, several studies of HAI such as urinary tract infections (UTIs) and catheter-associated urinary tract infections (CAUTIs) have shown contradictory results. The aim of this study is to assess the clinical features of UTIs and bacterial isolates from urine samples of hospitalized COVID-19 patients. We conducted a retrospective observational study including 87 COVID-19 patients with UTIs admitted to our centre. Bacterial UTIs presented were 87: 9 (10.3%) community-acquired UTIs (coinfection group) and 78 (89.6%) hospital-acquired UTIs (superinfection group). In the coinfection group, the most frequent type was non-CAUTI with 5 (55.5%) patients; however, the most frequent UTI in the superinfection group was CAUTI, with 53 (67.9%) patients. The median number of days of hospitalization in coinfected patients was lower than superinfection patients: 13 (IQR 11, 23) vs. 34 days (IQR 23, 47) p < 0.006. All UTI patients admitted to ICU, 38 (43.7%), belonged to the superinfection group. The mortality rate was 26.4% (23/87), 22/23 in the superinfection group. The most common microorganisms were E. coli 27 (28.4%), E. faecalis 25 (26.3%) and E. faecium 20 (21.1%). There was an increased incidence of E. faecalis and E. faecium in UTIs as well as hospital-acquired UTIs. This can be related to urethral catheterization during hospitalization, UCI admissions and the number of days of hospitalization.

Fidaxomicin monotherapy versus standard therapy combined with bezlotoxumab for treating patients with Clostridioides difficile infection at high risk of recurrence: a matched cohort study.

BACKGROUND: Both fidaxomicin and bezlotoxumab (used in combination with an antibiotic against Clostridioides difficile) achieve reductions in recurrence rates of C. difficile infection (CDI). However, the two strategies have never been compared. METHODS: Data from two retrospective cohorts of 'real-life' use of fidaxomicin and bezlotoxumab in combination with a standard anti-C. difficile antibiotic were used to compare the rates of recurrence of both strategies. Since the two cohorts were not identical, we used a propensity score analysis. RESULTS: Three hundred and two patients were included: 244 in the fidaxomicin cohort and 78 in the bezlotoxumab cohort. A history of renal failure or immunosuppression was more frequent in patients receiving bezlotoxumab (39.7% and 66.7% versus 26.6% and 38.9%; P = 0.03 and P < 0.001, respectively), but the severity and number of previous CDI episodes were similar in both cohorts. We observed that 19.3% of the patients in the fidaxomicin cohort experienced recurrence, compared with 14.1% in the bezlotoxumab cohort (OR 1.45; 95% CI 0.71-2.96; P = 0.29) but the difference remained non-significant after propensity score matching using previously defined variables (OR 1.24; 95% CI 0.50-3.07; P = 0.64). Moreover, the multivariate analysis did not show differences depending on the drug used. CONCLUSIONS: We observed that fidaxomicin and bezlotoxumab are prescribed in similar clinical scenarios, although those treated with bezlotoxumab have greater comorbidity. The proportion of recurrences was numerically lower in those treated with bezlotoxumab, although the propensity analysis did not find significant differences between the two drugs.

Pacemaker pocket infection by Nocardia carnea. First case description and literature review.

Acid-fast gram-positive bacilli are a seldom causal agent of cardiac implantable electronic devices (CIED) infections. A pacemaker pocket infection by Nocardia carnea is presented. The objective of this review is to know the incidence of pacemaker pocket infection by Nocardia and to collect information to contribute to the management of this infection. We describe both our case and those found in the literature. Only three cases were found. Two of the patients were older than 70 years without immunosuppression, presenting erythema at the pacemaker implantation site as main symptom. Bloodstream infection was registered in one of them. Three microorganisms were sensitive to cotrimoxazole. The minimum time of antibiotic therapy was 6 weeks. An incomplete device removal was done in one case, resulting in an unfavorable clinical course. The incidence of pacemaker pocket infection by these microorganisms is low, resolved in most cases with antibiotic treatment and device removal.

Concurrent Stroke and Myocardial Infarction After Mild COVID-19 Infection.

INTRODUCTION: The concurrency of both, acute stroke and acute myocardial infarction in normal conditions, outside the pandemic is rare. Coagulopathy has been associated with the inflammatory phase of coronavirus disease (COVID-19) and might be involved in this concurrency. CASES REPORT: We describe 2 patients with previous mild or no symptoms of COVID-19, admitted for acute stroke with recent/simultaneous myocardial infarction in whom admission polymerase chain reaction was negative but serologic testing diagnosed COVID-19. In these patients, concurrent stroke and myocardial infarction could have been promoted by COVID-19 infection. Management and evolution are detailed, and their contacts to confirm the COVID-19 infection. Pathogenic analysis of possible hypercoagulation state is described suggesting the hypothesis of endothelial dysfunction as the strongest mechanism involved in thrombus formation after the acute phase of COVID-19 infection. CONCLUSIONS: Our experience with these cases suggests that patients with mild symptoms can also present thromboembolic complications once the acute phase of COVID-19 infection has passed.

Characterization of an osteomyelitis case caused by dalbavancin, ceftaroline, and vancomycin non-susceptible methicillin-resistant Staphylococcus aureus.

We report a case of osteomyelitis due to methicillin-resistant Staphylococcus aureus (MRSA) that is also non-susceptible to vancomycin, dalbavancin, ceftaroline, and ceftobiprole, in the absence of exposure to the latter three antibiotics. It was isolated from a patient with a 26-year history of cranial surgeries and episodes of osteomyelitis. Whole-genome sequencing was performed. It was found to belong to ST247 and the mecA gene was detected within the SSCmec type I (1B) gene cassette that lacked the E447K mutation known to produce resistance to ceftobiprole and ceftaroline. However, mutations in other genes related to resistance to these antibiotics were found.

Characteristics of patients with suspected COVID-19 pneumonia and repeatedly negative RT-PCR.

OBJECTIVES: Challenges remain and there are still a sufficient number of cases with epidemiological, clinical features and radiological data suggestive of COVID-19 pneumonia that persist negative in their RT-PCR results. The aim of the study was to define the distinguishing characteristics between patients developing a serological response to SARS-CoV-2 and those who did not. METHODS: RT-PCR tests used were TaqPath 2019-nCoV Assay Kit v1 (ORF-1ab, N and S genes) from Thermo Fisher Diagnostics and SARS-COV-2 Kit (N and E genes) from Vircell. Serological response was tested using the rapid SARS-CoV2 IgG/IgM Test Cassette from T and D Diagnostics Canada and CMC Medical Devices and Drugs, S.L, CE. RESULTS: In this cross-sectional study, we included a cohort of 52 patients recruited from 31 March 2020 to 23 April 2020. Patients with positive serology had an older average age (73.29) compared to those who were negative (54.82) (P<0.05). Sat02 in 27 of 34 patients with positive serology were below 94% (P<0.05). There was a frequency of 1.5% negative SARS-CoV-2 RT-PCRs during the study period concurring with 36.7% of positivity. CONCLUSION: Clinical features and other biomarkers in a context of a positive serology can be considered crucial for diagnosis.

Intestinal loads of OXA-48-producing Klebsiella pneumoniae in colonized patients determined from surveillance rectal swabs.

OBJECTIVES: To determine quantitatively the extent of intestinal colonization by OXA-48-producing Klebsiella pneumoniae (KpOXA) in hospitalized patients. METHODS: The load of the OXA-48 ß-lactamase gene in rectal swabs from 147 colonized patients was measured by quantitative PCR. The load was calculated relative to the total bacterial population (represented by the 16S rRNA gene) using the ΔΔCt method and pure cultures of OXA-48-producing K. pneumoniae as reference samples. The relative loads of the epidemic K. pneumoniae clones ST11 and ST405 were also measured. RESULTS: The relative intestinal loads of the OXA-48 ß-lactamase gene, RLOXA-48, in hospitalized patients were high. The median RLOXA-48 was -0.42 (95% confidence interval (CI): -0.60 to -0.16), close to that of a pure culture of OXA-48-producing K. pneumoniae (RLOXA-48 = 0). In those patients colonized by the KpOXA clones ST11 (51/147, 34.7%) and ST405 (14/147, 9.5%), the relative loads of these clones were similarly high (median RLST11 = -1.1, 95% CI: -1.64 to -0.92; median RLST405 = -1.3, 95% CI: -1.76 to -0.96). Patients that had received previous antibiotic treatments and those that developed infections by KpOXA had significantly higher RLOXA-48 values: -0.32 (95% CI: -0.58 to -0.20) vs -1.07 (95% CI: -2.43 to -0.35) and -0.26 (-0.77 to -0.23) vs -0.47 (-0.74 to -0.28), respectively. CONCLUSIONS: Colonization by KpOXA in hospital patients involves intestinal loads much higher than the K. pneumoniae loads reported in the normal microbiota, reaching levels close to those of pure KpOXA cultures in many cases and largely replacing the host microbiota.

Real-World Experience with Bezlotoxumab for Prevention of Recurrence of Clostridioides difficile Infection.

Bezlotoxumab is marketed for the prevention of recurrent Clostridioides difficile infection (rCDI). Its high cost could be determining its prescription to a different population than that represented in clinical trials. The objective of the study was to verify the effectiveness and safety of bezlotoxumab in preventing rCDI and to investigate factors related to bezlotoxumab failure in the real world. A retrospective, multicentre cohort study of patients treated with bezlotoxumab in Spain was conducted. We compared the characteristics of cohort patients with those of patients treated with bezlotoxumab in the pivotal MODIFY trials. We assessed recurrence rates 12 weeks after completion of treatment against C. difficile, and we analysed the factors associated with bezlotoxumab failure. Ninety-one patients were included in the study. The cohort presented with more risk factors for rCDI than the patients included in the MODIFY trials. Thirteen (14.2%) developed rCDI at 12 weeks of follow-up, and rCDI rates were numerically higher in patients with two or more previous episodes (25%) than in those who had fewer than two previous episodes of C. difficile infection (CDI) (10.4%); p = 0.09. There were no adverse effects attributable to bezlotoxumab. Despite being used in a more compromised population than that represented in clinical trials, we confirm the effectiveness of bezlotoxumab for the prevention of rCDI.

Isolation of Aspergillus spp. in respiratory samples of patients with COVID-19 in a Spanish Tertiary Care Hospital.

BACKGROUND: Invasive pulmonary aspergillosis (IPA) is a complication of respiratory bacterial and viral infections such as coronavirus disease 2019 (COVID-19). PATIENTS/METHODS: In University Hospital La Paz (Madrid, Spain), we reviewed the clinical and demographic characteristics of 10 patients with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR and Aspergillus spp. isolate in respiratory samples. We also recovered results of galactomannan tests in serum and/or bronchoalveolar lavage (BAL) samples. RESULTS: Eight male and two female from 51 to 76 years were recovered. They had reported risk factors to develop IPA (haematological malignancies, immunosuppression, diabetes, obesity, intensive care unit stay, among others). Azole susceptible Aspergillus fumigatus was isolated in nine patients and Aspergillus nidulans was isolated in one patient. Only one case was classified as probable aspergillosis, seven cases as putative aspergillosis, and two cases were not classifiable. Eight patients received antifungal treatment. Seven patients died (70%), two are still inpatient due to nosocomial infections and one was discharged referred to another institution. CONCLUSIONS: This clinical entity has high mortality, and therefore, it should be performed surveillance with early galactomannan tests and cultures in respiratory samples in order to improve the outcome of the patients with this condition.

Linezolid for therapy of Staphylococcus aureus meningitis: a cohort study of 26 patients.

BACKGROUND: Linezolid has good penetration to the meninges and could be an alternative for treatment of Staphylococcus aureus meningitis. We assessed the efficacy and safety of linezolid therapy for this infection. METHODS: Retrospective multicenter cohort study of 26 adults treated with linezolid, derived from a cohort of 350 cases of S. aureus meningitis diagnosed at 11 university hospitals in Spain (1981-2015). RESULTS: There were 15 males (58%) and mean age was 47.3 years. Meningitis was postoperative in 21 (81%) patients. The infection was nosocomial in 23 (88%) cases, and caused by methicillin-resistant S. aureus in 15 cases and methicillin-susceptible S. aureus in 11. Linezolid was given as empirical therapy in 10 cases, as directed therapy in 10, and due to failure of vancomycin in 6. Monotherapy was given to 16 (62%) patients. Median duration of linezolid therapy was 17 days (IQR 12-22 days) with a daily dose of 1,200 mg in all cases. The clinical response rate to linezolid was 69% (18/26) and microbiological response was observed in 14 of 15 cases evaluated (93%). Overall 30-day mortality was 23% and was directly associated with infection in most cases. When compared with the patients of the cohort, no significant difference in mortality was observed between patients receiving linezolid or vancomycin for therapy of methicillin-resistant S. aureus meningitis (9% vs. 20%; p = .16) nor between patients receiving linezolid or cloxacillin for therapy of methicillin-susceptible S. aureus meningitis (20% vs 14%; p = .68). Adverse events appeared in 14% (3/22) of patients, but linezolid was discontinued in only one patient. CONCLUSIONS: Linezolid appears to be effective and safe for therapy of S. aureus meningitis. Our findings showed that linezolid may be considered an adequate alternative to other antimicrobials in meningitis caused by S. aureus.