The antimicrobial activity of zinc against group B Streptococcus is strain-dependent across diverse sequence types, capsular serotypes, and invasive versus colonizing isolates

Background Streptococcus agalactiae or Group B Streptococcus (GBS) is an encapsulated gram-positive bacterial pathobiont that commonly colonizes the lower gastrointestinal tract and reproductive tract of human hosts. This bacterium can infect the gravid reproductive tract and cause invasive infections of pregnant patients and neonates. Upon colonizing the reproductive tract, the bacterial cell is presented with numerous nutritional challenges imposed by the host. One strategy employed by the host innate immune system is intoxication of bacterial invaders with certain transition metals such as zinc. Methodology Previous work has demonstrated that GBS must employ elegant strategies to circumnavigate zinc stress in order to survive in the vertebrate host. We assessed 30 strains of GBS from diverse isolation sources, capsular serotypes, and sequence types for susceptibility or resistance to zinc intoxication. Results Invasive strains, such as those isolated from early onset disease manifestations of GBS infection were significantly less susceptible to zinc toxicity than colonizing strains isolated from rectovaginal swabs of pregnant patients. Additionally, capsular type III (cpsIII) strains and the ST-17 and ST-19 strains exhibited the greatest resilience to zinc stress, whereas ST-1 and ST-12 strains as well as those possessing capsular type Ib (cpsIb) were more sensitive to zinc intoxication. Thus, this study demonstrates that the transition metal zinc possesses antimicrobial properties against a wide range of GBS strains, with isolation source, capsular serotype, and sequence type contributing to susceptibility or resistance to zinc stress.

Indirect effects of the covid-19 pandemic on childhood infection in England: population based observational study

ObjectiveTo assess the impact of the covid-19 pandemic on hospital admission rates and mortality outcomes for childhood respiratory infections, severe invasive infections, and vaccine preventable disease in England.DesignPopulation based observational study of 19 common childhood respiratory, severe invasive, and vaccine preventable infections, comparing hospital admission rates and mortality outcomes before and after the onset of the pandemic in England.SettingHospital admission data from every NHS hospital in England from 1 March 2017 to 30 June 2021 with record linkage to national mortality data.PopulationChildren aged 0-14 years admitted to an NHS hospital with a selected childhood infection from 1 March 2017 to 30 June 2021.Main outcome measuresFor each infection, numbers of hospital admissions every month from 1 March 2017 to 30 June 2021, percentage changes in the number of hospital admissions before and after 1 March 2020, and adjusted odds ratios to compare 60 day case fatality outcomes before and after 1 March 2020.ResultsAfter 1 March 2020, substantial and sustained reductions in hospital admissions were found for all but one of the 19 infective conditions studied. Among the respiratory infections, the greatest percentage reductions were for influenza (mean annual number admitted between 1 March 2017 and 29 February 2020 was 5379 and number of children admitted from 1 March 2020 to 28 February 2021 was 304, 94% reduction, 95% confidence interval 89% to 97%), and bronchiolitis (from 51 655 to 9423, 82% reduction, 95% confidence interval 79% to 84%). Among the severe invasive infections, the greatest reduction was for meningitis (50% reduction, 47% to 52%). For the vaccine preventable infections, reductions ranged from 53% (32% to 68%) for mumps to 90% (80% to 95%) for measles. Reductions were seen across all demographic subgroups and in children with underlying comorbidities. Corresponding decreases were also found for the absolute numbers of 60 day case fatalities, although the proportion of children admitted for pneumonia who died within 60 days increased (age-sex adjusted odds ratio 1.71, 95% confidence interval 1.43 to 2.05). More recent data indicate that some respiratory infections increased to higher levels than usual after May 2021.ConclusionsDuring the covid-19 pandemic, a range of behavioural changes (adoption of non-pharmacological interventions) and societal strategies (school closures, lockdowns, and restricted travel) were used to reduce transmission of SARS-CoV-2, which also reduced admissions for common and severe childhood infections. Continued monitoring of these infections is required as social restrictions evolve.

Revendo o tratamento para pneumonia causada por Staphylococcus aureus resistente à meticilina

Introduction: Methicillin-resistant Staphylococcus aureus (MRSA) can cause several infections, both dermatological and invasive infections, such as pneumonia, empyema and sepsis. Due to its importance and pathogenicity, it is considered a worldwide public health problem, which implies the need to search for more efficient therapeutic regimens. Specifically for the treatment of MRSA pneumonia, vancomycin and linezolid are the main drugs used. Objective: The main objective of this study was to compare the two drugs in terms of their effectiveness in the treatment of MRSA pneumonia, through a review of the most recent aspects of the literature. Methodology: Through a narrative review, the pros and cons of each therapeutic intervention were investigated, as well as the individual pharmacological aspects and the pathophysiology of the bacterial infection in question. Conclusion: Finally, it was concluded that linezolid is superior to vancomycin, with better rates of reduced mortality and length of hospital stay, along with a lower risk of complications and adverse events, in addition to greater therapeutic flexibility, better cost-effectiveness and lower resistance rates.

Genomic Characterization of Streptococcus suis Serotype 24 Clonal Complex 221/234 From Human Patients

Streptococcus suis is a zoonotic pathogen that causes invasive infections in humans and pigs. Although S. suis serotype 2 is prevalent among patient and swine infections, other serotypes are occasionally detected in humans. Of these, serotype 24 clonal complex (CC) 221/234 are recognized as emerging clones of human infection. Genomic exploration of three S. suis serotype 24 CC221/234 strains revealed antimicrobial resistance genes, pathotyping, virulence-associated gene (VAG) profiles, minimum core genome (MCG) typing, and comparison of the genomes. Based on these analyzes, all three serotype 24 strains were MCG7-3 and should be classified in the intermediate/weakly virulent (I/WV) group. All selected serotype 24 strains were susceptible to several antibiotics including β-lactam, fluoroquinolone, and chloramphenicol. Resistance to tetracycline, macrolide, and clindamycin was observed and attributed to the genes tet(O) and erm(B). Genomic comparison revealed the strains S12X, LSS66, LS0L, LS0E, 92–4,172, and IMT40201 that had phylogenetic affinity with serotype 24 CC221/234. Analysis of 80 virulence-associated genes (VAG) showed that all three serotype 24 strains lacked 24 genes consisting of adhesin P, epf, hyl, ihk, irr, mrp, nadR, neuB, NisK/R, ofs, permease (SSU0835), rgg, revS, salK/R, sao, sly, spyM3_0908, srtBCD, srtF, srtG, SSU05_0473, virA, virB4, and virD4. Eleven specific sequences were identified in the 3 serotype 24 genomes that differed from the genomes of the representative strains of epidemic (E; SC84), highly virulent (HV; P1/7), I/WV (89–1,591), and avirulent (T15 and 05HAS68).

Bloodstream infections caused by Magnusiomyces capitatus and Magnusiomyces clavatus: epidemiological, clinical and microbiological features of two emerging yeast species

Background: Magnusiomyces clavatus and Magnusiomyces capitatus are emerging yeasts with intrinsic resistance to many commonly used antifungal agents. Identification is difficult, and determination of susceptibility patterns with commercial and reference methods is equally challenging. For this reason, few data on invasive infections by Magnusiomyces spp. are available. Objectives: To determine the epidemiology and susceptibility of Magnusiomyces isolates from bloodstream infections (BSI) isolated in Germany and Austria from 2001-2020. Methods: In seven institutions a total of 34 Magnusiomyces BSI were identified. Identification was done by ITS sequencing and MALDI-TOF MS. Antifungal susceptibility was determined by EUCAST broth microdilution and gradient tests. Results: Of the 34 isolates, M. clavatus was more common (N=24) compared to M. capitatus (N=10). BSI by Magnusiomyces spp. were more common in men (62%) and mostly occurred in patients with haemato-oncological malignancies (79%). The highest in vitro antifungal activity against M. clavatus / M. capitatus was observed for voriconazole (MIC 50 0.03/0.125 mg/L), followed by posaconazole (MIC 50 0.125/0.25 mg/L). M. clavatus isolates showed overall lower MICs compared to M. capitatus . With the exception of amphotericin B, low essential agreement between gradient test and microdilution was recorded for all antifungals (0-70%). Both species showed distinct morphologic traits on ChromAgar Orientation and Columbia blood agar, which can be used for differentiation if no MALDI-TOF or molecular identification is available. Conclusion: Most BSI were caused by M. clavatus. The lowest MICs were recorded for voriconazole. Gradient tests demonstrated unacceptably low agreement and should preferably not be used for susceptibility testing of Magnusiomyces spp.

Candida auris gene expression: modulation upon caspofungin treatment

Candida auris has emerged as a serious worldwide threat by causing invasive infections in humans that are frequently resistant to one or more conventional antifungal medications, resulting in high mortality rates. Against this backdrop, health warnings around the world have focused efforts on understanding C. auris fungal biology and effective treatment approaches to combat this fungus. To date, there is little information about C. auris gene expression regulation in response to antifungal treatment. Our integrated analyses focused on the comparative transcriptomics of C. auris in the presence and absence of caspofungin as well as a detailed analysis of the yeast's extracellular vesicle (EV)-RNA composition. The results showed that genes coding oxidative stress response, ribosomal proteins, cell wall, and cell cycle were significantly up-regulated in the presence of caspofungin, whereas transcriptional regulators and proteins related to nucleus were down-regulated. The mRNAs in the EVswere associated with the stress responses induced by caspofungin and the ncRNA content of the EVs shifted during caspofungin treatment. Altogether, the results provide further insights into the fungal response to caspofungin and demonstrate that analyses of C. auris growth under antifungal stress can elucidate resistance and survival mechanisms of this fungus in response to medical therapy.

Invasive Group B Streptococcal Disease in Neonates and Infants, Italy, Years 2015–2019

Invasive infections by group B streptococci (iGBS) are the leading cause of sepsis and meningitis in the first three months of life worldwide. The clinical and microbiological characteristics of neonatal and infant iGBS in Italy during the years 2015–2019 were investigated. Voluntary-based surveillance reported 191 cases (67 early-onset (EOD) and 124 late-onset disease (LOD)) and 89 bacterial isolates were received. The main clinical manifestations were sepsis (59.2%) followed by meningitis (21.5%), bacteremia (12.0%) and septic shock (6.3%). Hospitalized preterm babies accounted for one third of iGBS and constituted the most fragile population in terms of mortality (8.2%) and brain damage (16.4%). GBS serotype III was predominant in EOD (56%) and caused almost all LOD (95%). The rate of resistance to clindamycin reached 28.8%. Most of clindamycin-resistant GBS strains (76%) were serotype III-ST17 and possessed the genetic markers of the emerging multidrug resistant (MDR) CC-17 sub-clone. Our data revealed that iGBS is changing since it is increasingly reported as a healthcare-associated infection (22.6%), mainly caused by MDR-CC17. Continuous monitoring of the clinical and microbiological characteristics of iGBS remains of primary importance and it represents, at present, the most effective tool to support prevention strategies and the research on the developing GBS vaccine.

Comparison of Trimethoprim-Sulfamethoxazole vs. Clindamycin for the Treatment of Children with Musculoskeletal Infections

Background: Musculoskeletal infections ([MSKI]; osteomyelitis, septic arthritis, pyomyositis) are common invasive infections in children. With increasing antibiotic resistance and allergies, treatment options are limited. Trimethoprim-sulfamethoxazole (TMP-SMX) has activity against common MSKI pathogens, yet pediatric MSKI outcomes data are limited. Our aim was to evaluate outcomes of children with MSKI treated with TMP-SMX compared to clindamycin. We hypothesized that outcomes would be similar between groups. Methods: We conducted a retrospective review of children <18 years old, admitted to Riley Hospital for Children from January 2010-June 2021 treated with TMP-SMX or clindamycin for MSKI. Patients were identified by ICD-9/10 codes. Patients were excluded if TMP-SMX or clindamycin was not the main treatment, they had symptoms >30 days, hardware associated infection, or an alternative diagnosis. Treatment success was defined as no evidence of infection at the end therapy. Treatment failure was defined as antibiotic intolerance, or development of recurrent/chronic osteomyelitis. Adverse drug reactions were recorded. Results: One-hundred-sixty-three patients (30 TMP-SMX, 133 clindamycin) met eligibility criteria. The majority were non-Hispanic white males, median age of 1.75 years (IQR, 1-3.75) for the TMP-SMX group, and 7 years (IQR 3-10) for the clindamycin group. Osteomyelitis was the most common infection type in both groups (TMP-SMX 43.3%, clindamycin 54.1%). S. aureus was the most common pathogen in both groups (TMP-SMX 36.7%, clindamycin 48.1%). Of the patients that completed follow-up, 84% successfully completed treatment with TMP-SMX, compared to 86.4% with clindamycin (odds ratio [OR] 0.82; 95% CI 0.25-2.46, p=0.75). Adverse drug reactions occurred in 6.7% of the TMP-SMX group, compared to 10.5% in the clindamycin group (OR 0.61; 95% CI 0.13-2.57, p=0.52). Conclusions: Preliminary results show that TMP-SMX is well tolerated and not associated with higher risk of treatment failure compared to clindamycin in the treatment of pediatric MSKI. Randomized controlled trials to evaluate optimal treatment are needed.