Infectious diseases (London, England)最新文献

Background: Ceftolozane/tazobactam (C/T) in combination with metronidazole is an active antimicrobial therapy used to treat complicated intra-abdominal infections (cIAIs).

Methods: A comparison of the clinical efficacy of C/T plus metronidazole vs. meropenem for the treatment of cIAIs using pooled data from four phase 3 clinical studies (CXA-cIAI-10-08, CXA-cIAI-10-09, NCT02739997 and NCT03830333).

Results: In total, 1,361 patients (C/T plus metronidazole, n = 721; meropenem, n = 640) were included in the pooled analysis. Clinical response rates at the test of cure (TOC) visit in the intention-to-treat (ITT) and clinically evaluable populations were 84.3% (608/721) and 86.9% (556/640) as well as 93.4% (534/572) and 93.8% (483/515), and at the end of treatment visits the rates were 90.6% (653/721) and 91.9% (588/640) as well as 96.5% (552/572) and 96.6% (499/515) for C/T plus metronidazole and meropenem, respectively. Microbiological response rates at the TOC visits in the modified ITT population were 85.3% (440/516) and 89.3% (442/495), and in the extended microbiological evaluable population 93.7% (399/426) and 94.3% (394/418) for C/T plus metronidazole and meropenem, respectively. Adverse events occurred in 341/716 (47.6%) and 280/631 (44.4%) patients treated with C/T plus metronidazole and meropenem, respectively. The most common adverse events across treatment groups were diarrhoea, nausea, pyrexia and insomnia. No new serious safety findings were identified.

Conclusions: The efficacy of C/T plus metronidazole was comparable with meropenem even for cIAIs and C/T plus metronidazole might be an alternative treatment option for cIAI.

Background: Tuberculosis (TB) remains a major public health issue in Bengaluru, India. This study analyzes TB trends, treatment outcomes, and the impact of COVID-19 on TB incidence from 2017 to 2023.

Methods: Logistic regression analysis was used to identify factors influencing TB treatment outcomes. An Interrupted Time Series (ITS) analysis using an ARIMA (AutoRegressive Integrated Moving Average) model was used to assess the impact of COVID-19 on TB incidence.

Results: Among 71,883 TB cases, age ≥65 years had increased the risk of unsuccessful outcomes for pulmonary TB (PTB) (adjusted odds ratio [aOR] 2.54; 95% confidence interval [CI], 2.24-2.89) and extrapulmonary TB (EPTB) (aOR 3.72; CI, 3.06-4.52). Females had lower odds than males in PTB (aOR 0.72; CI, 0.67-0.78) and EPTB (aOR 0.77; CI, 0.68-0.86). Diabetics had lowered risk for PTB (aOR 0.62; CI, 0.57-0.68) but increased risk for EPTB (aOR 1.44; CI, 1.24-1.67). HIV cases had increased risk in PTB (aOR 1.96; CI, 1.67-2.31) and EPTB (aOR 2.88; CI, 2.32-3.57). Interaction analysis in PTB showed diabetics with ages 35-44 and 45-54 was associated with lower risk (aOR 0.66; CI, 0.44-0.99; aOR 0.67; CI, 0.46-0.99). ITS analysis showed a 24.3% average decline in TB notifications in 2020, reaching a maximum decline of 40.5% in April.

Conclusion: This study highlights factors affecting TB treatment outcomes and the significant impact of COVID-19 on TB trends in Bengaluru, providing insights to improve TB control and mitigate future pandemic impacts.

In May 2024 with a subsequent update in June 2025, the Swedish Medical Products Agency's expert group revised guidelines on the management and treatment of respiratory syncytial virus (RSV) infection. This is an abridged version and commentary on the full recommendation including specific recommendations for the RSV-season 2025/2026. Key points are: (i) RSV is a seasonal, highly contagious infection. Almost all children are infected by age two, usually with mild illness; (ii) Some infants, children with underlying conditions, and frail elderly are at risk for developing severe disease requiring hospital care; (iii) Preventive measures-such as hand hygiene and avoiding contact with people with colds-are essential to protect infants and the elderly; (iv) Prophylactic treatment with monoclonal antibodies reduces the risk of infants developing severe RSV disease and requiring hospital care. The long-acting drug nirsevimab is preferred over the shorter-acting palivizumab; (v) Universal prophylaxis in infants reduce disease burden for both families and society; (vi) If supply is limited, children at highest risk should be prioritised for prophylaxis; (vii) Maternal vaccination during pregnancy lowers the risk of severe RSV in newborns, decreasing hospital admissions. The protective effect is considered to be equivalent to that of monoclonal antibodies. Recommendations and funding decision for maternal vaccination is under investigation during the autumn of 2025; (viii) In the elderly, vaccination is the most effective pharmacological prevention; (ix) There is no effective antiviral treatment for established RSV disease; management is symptomatic and supportive. Hospitalised children should not be subjected to measures with no proven effect, preferable minimal interventions, with treatment focused on ensuring adequate nutrition; (x) The Swedish recommendations state that during the RSV season 2025/2026, nirsevimab should be administered to prevent RSV infection in all infants aged 0-3 months during the RSV season and to infants under 12 months with increased risk of severe RSV and certain high risk children under 24 months.

Background: Pneumonia is a major cause of morbidity and mortality, yet causative organisms are rarely identified. Metagenomic next-generation sequencing (mNGS) may improve this, however the impact on outcomes is uncertain and the relative utility in pneumonia subtypes or different clinical samples is unclear.

Methods: This systematic review compared mNGS with conventional microbiology, assessing pathogen identification, turnaround time and clinical impact. It also reviewed difference related to the pneumonia subtype, or sample used. We searched EMBASE, MEDLINE, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL) for studies comparing mNGS with conventional microbiology, in patients with pneumonia. All study types were included (excluding case reports of <10 people). Eligibility assessment and data extraction was performed by two independent reviewers, and risk of bias assessed using the QUADAS-2.

Results: We identified 74 studies including 10,566 people, with all studies having high risk of bias or applicability concerns in at least one domain. Conventional tests identified a pathogen in 43.2% of cases (3559/8229) compared to 78.9% for mNGS (6242/7980). mNGS had faster turnaround times than conventional microbiology (MD -73.6h, CI-111.36 - -35.73 hrs) but meta-analysis was not possible for other outcomes. Most studies did not specify the pneumonia subtype. 92%of studies used exclusively or predominantly bronchoalveolar lavage fluid (BALF), and the utility of other sample types could not be established.

Conclusions: mNGS may identify possible pathogens with greater frequency than standard techniques although bias in study design limits definite conclusions, and the clinical relevance of this remains unresolved. There is a need for studies assessing clinical outcomes, and the differential impact in pneumonia subtypes and in samples other than BALF.

Objectives: This study aims to compare risk factors and mortality of candidemia by Candida auris versus Candida non-auris in intensive care units (ICU).

Methods: A total of 437 ICU patients who developed candidemia (90 C. auris, 143 C. albicans, 204 other Candida spp.) in 2021-2023 were included. The risk factors in candidemia caused by C. auris, C. albicans and other Candida spp. were compared. Factors associated with 30-day mortality in C. auris candidemia were explored.

Results: Compared to the C. albicans group, the C. auris group had more frequent ceftazidime avibactam use (OR:6.72, 95%CI: 1.29-34.98, p = 0.024) and tracheostomy (OR:4.13, 95%CI: 1.70-10.02, p = 0.002), longer colistin (OR:1.07, 95%CI: 1.01-1.13, p = 0.021) and urinary catheter use (OR:1.02, 95%CI: 1.01-1.03, p = 0.023). Compared to the other Candida spp. group, colistin use (OR:2.79, 95%CI: 1.61-4.87, p < 0.001), chronic obstructive pulmonary disease (OR:2.02, 95%CI: 1.05-3.90, p = 0.036) and concurrent bacteraemia (OR:1.92, 95%CI: 1.06-3.48, p = 0.030) were more frequent in the C. auris group. Rate of 30-day mortality was lower in C. auris patients (63.3%) compared to the C. albicans (82.5%) and other Candida spp. (75.5%) groups. While the 30-day mortality rate was higher in C. auris patients who received vasopressor therapy (OR:3.12, 95%CI: 1.78-5.47, p < 0.001) and had high lactate levels (OR:1.41, 95%CI: 1.00-1.99, p = 0.047) and low platelet counts (OR:1.00, 95%CI: 0.99-1.00, p = 0.003) on the first day of candidemia, it was lower in patients with microbiologic response (OR:0.03, 95%CI: 0.01-0.09, p < 0.001).

Conclusion: The necessity of broad-spectrum antibiotics and indwelling catheters should be routinely reassessed to reduce C. auris candidemia. Lower mortality was linked to microbiologic response; thus, fungal eradication should be prioritised in clinical practice.

Background: Cutibacterium acnes is a cause of implant-associated infections, often co-occurring with methicillin-susceptible Staphylococcus aureus (MSSA), especially in orthopedic settings. In Scandinavia, cloxacillin may be used as initial empiric intravenous treatment if MSSA implant-associated infection is suspected. Clinical breakpoints for C. acnes susceptibility to cloxacillin or other isoxazolyl-penicillins are lacking to guide therapy if C. acnes is subsequently cultured after empiric cloxacillin therapy has been initiated.

Objective: We aimed to compare MIC distributions of C.acnes to benzylpenicillin and cloxacillin. Furthermore, we investigated if the gradient test is a reliable method for determining cloxacillin susceptibility in clinical C. acnes isolates in order to manage mixed infections in orthopedic settings.

Methods: We evaluated the in vitro susceptibility of 39 clinical C. acnes isolates to benzylpenicillin and cloxacillin using gradient tests and validated cloxacillin MICs by agar dilution.

Results: All isolates were susceptible to benzylpenicillin (MIC ≤0.064 mg/L) and cloxacillin (MIC ≤0.5 mg/L), with MIC₅₀ values of 0.016 mg/L and 0.125 mg/L, respectively. The cloxacillin MIC distribution for C. acnes closely resembled that of S. aureus, suggesting that susceptibility to cloxacillin may be inferred from benzylpenicillin susceptibility. Gradient test results for cloxacillin showed high agreement with agar dilution (essential agreement 0.87), supporting its use as a practical alternative to agar dilution cloxacillin MIC determination if susceptibility testing is necessary.

Conclusion: Our findings indicate that intravenous cloxacillin is an effective treatment of C. acnes infections, and that cloxacillin gradient testing is a convenient and reliable alternative for MIC determination for clinical laboratories.

Objectives: SKYVaricella^TM, a live attenuated varicella vaccine product, is known to increase the risk of herpes zoster (HZ) in vaccinated children. We investigated the impact of introducing the vaccine on HZ incidence in Korea since 2018.

Methods: This ecological study used medical records from the Health Insurance Review and Assessment Service in Korea. We present data on HZ incidence trend in children (<10 years) from 2010 to 2024. A change in HZ incidence trend was evaluated using linear regression analysis, with vaccine introduction as an interaction term. We then calculated the number of excess HZ cases due to the vaccine introduction in Korea.

Results: HZ incidence in children <10 years presented a downward trend that continuously declined from 2010 to 2018. This downward trend was reversed to an upward trend in children <5 years, whereas the decreasing trend in children aged 5-9 years continued after 2019. The change in trend in children <5 years in 2019 was statistically significant (p < 0.001). There were 6,484 excess HZ cases in children <5 years from January 2019 to June 2024.

Conclusions: The vaccine introduction has resulted in a large-scale ongoing HZ outbreak in children in Korea. More studies are needed to assess the long-term impact of the vaccine on HZ incidence in vaccinated individuals.

Background: Salmonella infections are a major cause of human illness in the United States. Salmonella enterica serotype Infantis has re-emerged as a leading serotype with the emergence of a multidrug-resistant S. Infantis strain, designated as REPJFX01 by the Centers for Disease Control and Prevention (CDC). REPJFX01, which typically contains a megaplasmid of emerging Salmonella Infantis (pESI) harbouring multiple resistance genes and a chromosomal gyrA87 mutation conferring decreased susceptibility to ciprofloxacin, has caused human infections linked to chicken consumption.

Objective: The study aimed to describe the epidemiology and antimicrobial resistance of human S. Infantis infections, including the emergence of REPJFX01, in the United States.

Methods: The study used data from five CDC surveillance systems, with combined years from 1979 through 2022. Negative binomial and logistic regression models were used in the multivariable analyses of surveillance data.

Results: In 10 active surveillance sites, the mean annual incidence of human S. Infantis infections was twice as high during 2013-2022 vs. 2003-2012 (adjusted rate ratio = 1.96, 95% CI 1.75-2.20). REPJFX01 infections accounted for nearly one-third of S. Infantis infections during 2018-2022 (vs. 2013-2017, adjusted odds ratio = 2.09, 95% CI 1.56-2.79). Salmonella Infantis infections were more likely among persons who were ≥45 years old, female, from racial and ethnic minority groups, and had Salmonella isolated from urine, than infections with other common serotypes.

Conclusion: The increase in S. Infantis infections during 2013-2022 was likely driven by an increase in REPJFX01 infections. Public health strategies to reduce Salmonella contamination of chicken could help prevent human infections.

Background: Staphylococcus aureus is the second most common cause of brain abscesses, but only few studies describe the disease characteristics.

Objectives: This study aimed to characterise the clinical features and outcomes of S. aureus brain abscess.

Methods: We identified all adults with a brain abscess caused by S. aureus in Denmark between 2007 and 2024, and at the Amsterdam UMC from 2016 to 2024. Unfavourable outcome was defined as Glasgow Outcome Scale scores of 1-4. Modified Poisson regression was used to assess relative risks (RR) with 95% confidence intervals (CI) for an unfavourable outcome.

Results: A total of 56 patients were identified with a median age of 59 years (interquartile range [IQR] 39-70), and 31/56 (55%) were male. Abscesses were mainly located in the frontal lobes (35/56, [63%]) and were due to head trauma or neurosurgery in 27/56 (48%). Patients with non-traumatic abscesses had predisposing otitis media or sinusitis in 9/29 (31%), whereas another 9/29 (31%) had endocarditis. Polymicrobial brain abscesses (Streptococcal species, anaerobic, and skin-colonising bacteria) were observed in 14/56 (25%) among whom 5/14 (36%) were post-traumatic and 9/14 (64%) were non-traumatic. Mortality at six months after discharge was 5/56 (9%), and 20/47 (43%) had an unfavourable outcome. The adjusted RR of an unfavourable outcome was 2.6 (95% CI 1.3-5.1) for post-traumatic abscess compared with non-traumatic S. aureus brain abscess.

Conclusions: Staphylococcus aureus brain abscess frequently involved the frontal lobes and a quarter were polymicrobial. Poor outcomes were common, especially among patients with post-traumatic abscesses.