Clinical and bacterial features of Group B streptococci with reduced penicillin susceptibility from respiratory specimens: a case–control studyNishiyama, Naoya; Kinjo, Takeshi; Uechi, Kohei; Parrott, Gretchen; Nakamatsu, Masashi; Tateyama, Masao; Fujita, Jiro
doi: 10.1007/s10096-021-04321-3pmid: 34383176
Streptococcus agalactiae (Group B Streptococcus, GBS) is an invasive pathogen that causes sepsis and meningitis among infants, elderly adults, and immunosuppressed patients. Generally, GBS is susceptible to penicillin; however, GBS with reduced penicillin susceptibility (PRGBS) has been reported. PRGBS are commonly isolated from respiratory specimens, but clinical features of patients with PRGBS remain unclear. In this case–control study, clinical features of patients with PRGBS and bacterial characteristics of these isolates from respiratory specimens were investigated. Patients with GBS at the University of the Ryukyus Hospital between January 2017 and June 2018 were retrospectively investigated. GBS were further classified into penicillin-susceptible GBS (PSGBS) and PRGBS using a drug susceptibility test. Moreover, serotypes, genotypes, and drug resistance genes of PRGBS isolates were determined. In total, 362 GBS were isolated, of which 46 were collected from respiratory specimens, which had the highest rate of PRGBS (24%). Compared to patients with PSGBS, those with PRGBS were more likely to have neuromuscular disease, poor performance status, risk of multidrug-resistant pathogen infection, prior pneumonia history within 1 year, and prior penicillin use within 1 year. Among eight PRGBS isolates, multilocus sequence typing revealed that five isolates were sequence type (ST) 358, two were ST3 and ST10, respectively, and one isolate was ST1404. All PRGBS isolates belonged to the ST1/ST19/ST10 group. This study reveals clinical characteristics of patients with PRGBS from respiratory specimens. Because invasive GBS infection cases are increasing, especially in the elderly, more attention should be paid to this infection.
Antibiotic stewardship program (ASP) in palliative care: antibiotics, to give or not to giveHung, Kai Chee; Lee, Lai Wei; Liew, Yi Xin; Krishna, Lalit; Chlebicki, Maciej Piotr; Chung, Shimin Jasmine; Kwa, Andrea Lay-Hoon
doi: 10.1007/s10096-021-04325-zpmid: 34414518
Antimicrobial therapy in terminally ill patients remains controversial as goals of care tend to be focused on optimizing comfort. International guidelines recommend for antibiotic stewardship program (ASP) involvement in antibiotic decisions in palliative patients. The primary objective was to evaluate the clinical impact of ASP interventions made to stop broad-spectrum intravenous antibiotics in terminally ill patients. This was a retrospective chart review of 459 terminally ill patients in Singapore General Hospital audited by ASP between December 2010 and December 2018. Antibiotic duration, time-to-terminal discharge for end-of-life care, time-to-mortality, and mortality rates of patients with antibiotics ceased or continued upon ASP recommendations were compared. A total of 283 and 176 antibiotic courses were ceased and continued post-intervention, respectively. The intervention acceptance rate was 61.7%. The 7-day mortality rate (47.3% vs 61.9%, p = 0.003) was lower in the ceased group, while 30-day mortality rate (76.0% vs 81.2%, p = 0.203) and time-to-mortality post-intervention (3 [0–24] vs 2 [0–27] days, p = 0.066) did not differ between the ceased and continued groups. After excluding the 57 patients who had antibiotics continued until death within 48 h of intervention, only time-to-mortality post-intervention was statistically significantly shorter in the ceased group (3 [0–24] vs 4 [0–27], p < 0.001). Of the 131 terminally discharged patients, antibiotic duration (4 [0–17] vs 6.5 [1–14] days, p = 0.001) and time-to-terminal discharge post-intervention (6 [0–74] vs 10.5 [3–63] days, p = 0.001) were shorter in the ceased group. Antibiotic cessation in terminally ill patients was safe, and was associated with a significantly shorter time-to-terminal discharge.
Dynamic changes in otopathogens colonizing the nasopharynx and causing acute otitis media in children after 13-valent (PCV13) pneumococcal conjugate vaccination during 2015–2019Kaur, Ravinder; Fuji, Naoko; Pichichero, Michael E.
doi: 10.1007/s10096-021-04324-0pmid: 34432166
The otopathogens colonizing the nasopharynx (NP) and causing acute otitis media (AOM) have shown dynamic changes following introduction of pneumococcal conjugate vaccines. Five hundred eighty-nine children were prospectively enrolled, 2015–2019. Two thousand fifty-nine visits (1528 healthy, 393 AOM, and 138 AOM follow-up) were studied. Two thousand forty-two NP and 495 middle ear fluid (MEF) samples by tympanocentesis from 319 AOM cases were cultured for bacterial identification and antibiotic susceptibility. Streptococcus pneumoniae (Spn) isolates were serotyped by Quellung, and multi-locus sequence type (ST) determined by genomic analysis. Haemophilus influenzae (Hi) was the most common otopathogen cultured from MEF during AOM (34% in MEF) followed by Spn (24% in MEF), then Moraxella catarrhalis (Mcat) (15% in MEF). NP isolates during healthy visit were Mcat (39%), Spn (32%), Hi (12%). 48.6% of Hi isolates from MEF were beta-lactamase-producing. Spn non-susceptibility to penicillin and other antibiotics was high. The most common Spn serotypes associated with AOM (and colonizing the NP during healthy visits) were 35B, 23B, and 15B/C. ST558 and ST199 were the most common sequence types. During 2015–2019, Hi was the most common otopathogen cultured from MEF during AOM among young children. Pneumococcal AOM was most commonly caused by non-PCV13 serotypes of Spn, predominantly 35B, 23B, and 15B/C. Resistance to common antibiotics among Spn strains showed an increasing trend.
Clinical characteristics, appropriateness of empiric antibiotic therapy, and outcome of Pseudomonas aeruginosa bacteremia across multiple community hospitalsTeelucksingh, Keith; Shaw, Eric
doi: 10.1007/s10096-021-04342-ypmid: 34462815
There is relatively little contemporary information regarding clinical characteristics of patients with Pseudomonas aeruginosa bacteremia (PAB) in the community hospital setting. This was a retrospective, observational cohort study examining the clinical characteristics of patients with PAB across several community hospitals in the USA with a focus on the appropriateness of initial empirical therapy and impact on patient outcomes. Cases of PAB occurring between 2016 and 2019 were pulled from 8 community medical centers. Patients were classified as having either positive or negative outcome at hospital discharge. Several variables including receipt of active empiric therapy (AET) and the time to receiving AET were collected. Variables with a p value of < 0.05 in univariate analyses were included in a multivariable logistic regression model. Two hundred and eleven episodes of PAB were included in the analysis. AET was given to 81.5% of patients and there was no difference in regard to outcome (p = 0.62). There was no difference in the median time to AET in patients with a positive or negative outcome (p = 0.53). After controlling for other variables, age, Pitt bacteremia score ≥ 4, and septic shock were independently associated with a negative outcome. A high proportion of patients received timely, active antimicrobial therapy for PAB and time to AET did not have a significant impact on patient outcome.
In vitro activity of cefiderocol against ceftazidime-avibactam susceptible and resistant KPC-producing Enterobacterales: cross-resistance and synergistic effectsBianco, Gabriele; Boattini, Matteo; Comini, Sara; Iannaccone, Marco; Bondi, Alessandro; Cavallo, Rossana; Costa, Cristina
doi: 10.1007/s10096-021-04341-zpmid: 34462816
PurposeTo assess the in vitro activity of cefiderocol (CFDC) against a collection of both ceftazidime-avibactam (CZA) susceptible and resistant KPC-producing Enterobacterales (KPC-EB) isolates. Secondly, to assess its synergistic activity in combination with different antibiotics.MethodsOne hundred KPC-EB isolates were tested: 60 CZA susceptible and 40 CZA resistant. Among them, 17 pairs of CZA susceptible and resistant KPC-producing Klebsiella pneumoniae (KPC-Kp) isolates were collected from 17 distinct patients before and after CZA treatment, respectively.CFDC susceptibility was evaluated by both broth microdilution (lyophilized panels; Sensititre; Thermo Fisher) and disk diffusion testing. Results were interpreted using EUCAST breakpoints. Synergistic activity of CFDC in combination with CZA, meropenem-vaborbactam, imipenem, and amikacin against six characterized KPC-Kp strains, before and after acquisition of CZA resistance, was evaluated using gradient diffusion strip crossing method.ResultsCFDC resistance rate was significantly higher in CZA resistant EB subset than in the susceptible one (p < 0.001): 82.5% vs 6.7%. MIC50 and MIC90 values were 0.25 and 2 mg/L, 8 and 64 mg/L in CZA-susceptible and CZA-resistant subset, respectively. KPC-Kp isolates harboring KPC-D179Y or KPC-Δ242-GT-243 variants showed CFDC MICs ranging from 4 to 64 mg/L. CFDC showed in vitro synergistic effect mostly with CZA, against both CZA susceptible and resistant isolates, resulting in a synergy rate of 66.7%.ConclusionsCZA resistance mechanisms in KPC-EB impair the in vitro activity of CFDC, often leading to co-resistance. CFDC in combination with the new β-lactamases inhibitors might represent a strategy to enhance its activity.
Appropriateness of empirical antibiotic prescription for bloodstream infections in an emergency department from 2006 to 2018: impact of the spread of ESBL-producing EnterobacteralesClemenceau, Marie; Ahmed-Elie, Samira; Vilfaillot, Aurelie; Chocron, Richard; Compain, Fabrice; Lebeaux, David; Grohs, Patrick
doi: 10.1007/s10096-021-04351-xpmid: 34553311
The spread of ESBL producers in the community may impact the management of patients with bloodstream infections (BSI) involving Enterobacterales in emergency departments. Thus, from 2006 to 2018, data for all BSI episodes involving Enterobacterales from the emergency department of a French teaching hospital were retrospectively included. Antimicrobial susceptibility test results and empirical antibiotic regimens were recorded. Treatment was considered as appropriate if all isolates were susceptible in vitro to at least one prescribed antibiotic. A total of 1369 BSI episodes in 1321 patients was included. Urinary tract infection was the main source of BSI (61%). The prevalence of ESBL producers increased from zero to 9.2/100 Enterobacterales BSI cases (p < 0.001), mainly Escherichia coli (6.9 cases/100 BSI in 2018); and no Klebsiella. Third-generation cephalosporins (3GC) were used most frequently (71.8%) and their use as monotherapy increased during the study period (p < 0.001). The rate of appropriate treatment decreased from 95.8 to 89.2% (p = 0.023). Appropriateness of treatment was greater using two drugs vs one (97.3% vs 89.3%, p < 0.001). Treatments with 3GC were appropriate in 92% and 98.3%, when used alone or with another antibiotic, respectively (p < 0.001). Among inappropriate treatments, 45% concerned 3GC, with 74.6% of them attributable to ESBL production. The spread of ESBL producers in the community had a direct impact on the rate of inappropriate empirical treatment. Local antimicrobial resistance monitoring is required to optimize the management of BSI in emergency departments.
Dynamic changes of inflammatory response and oxidative stress induced by methicillin-resistant Staphylococcus aureus in miceLong, Nana; Zhang, Yanjiao; Qiu, Min; Deng, Jingzhu; Sun, Fenghui; Dai, Min
doi: 10.1007/s10096-021-04349-5pmid: 34562152
This study is to analyze the dynamic changes of inflammation and oxidative stress in mice infected with MRSA and to provide experimental basis for clinically formulating reasonable treatment plans. We established a model of MRSA infection in mice, detected the fluctuations in the concentration of proinflammatory cytokines and oxidative stress factors with time, and combined with the results of microscopic examination of tissue sections to explain the infection in vivo caused by MRSA. The results showed that on the 1st, 3rd, and 7th day of MRSA infection, the number of leukocytes and eosinophils decreased at first and then increased, monocytes increased continuously, and neutrophils and basophils decreased. At the same time, the levels of proinflammatory cytokines IL-1β, IL-6, and TNF-α increased. The concentration of glutathione peroxide decreased, and the oxidative metabolites increased. Tissue sections also showed that inflammation and oxidative stress occurred in mice. It is obvious that MRSA infection can lead to significant inflammation and oxidative stress. Therefore, while treating MRSA infection, attention should be paid to the levels of inflammation and oxidative stress in different periods to achieve better treatment effects.