Presence of Streptococcus pyogenes in the throat in invasive Group A Streptococcal disease: a prospective two-year study in two health districts, Finland.

PURPOSE: Streptococcus pyogenes (Group A Streptococcus, GAS) is an important human pathogen that can cause severe invasive (iGAS) infections. Throat carriage has been assumed to possibly lead to hematogenous seeding. Retrospective studies may estimate the incidence of throat carriage in iGAS patients inaccurately. In this study we aimed to gather data on the presence of GAS in the throat among iGAS patients in a prospective setting. METHODS: We conducted a prospective clinical study covering iGAS infections in adult patients in two university hospitals in Finland from June 2018 to July 2020. Recruited patients' throats were swabbed for culture and isothermal amplification tests (IAT) to search for GAS. The study was registered at ClinicalTrials.gov as ID NCT03507101. RESULTS: We enrolled 45 patients. Throat swabs were obtained from 39/45 (87%) patients. Ten patients (22%) had a positive IAT for GAS. They were statistically significantly more likely to be male (9/10 [90%] vs 13/29 [45%], p = .024). Several different emm types caused the iGAS infections. CONCLUSIONS: GAS was frequently observed in throat swabs of patients with iGAS infection. This may suggest that hematogenous seeding from the nasopharynx is a possible portal of entry.

Acute kidney injury in group A streptococcal bacteraemia: incidence, outcome and predictive value of C-reactive protein.

BACKGROUND: A ubiquitous human pathogen, Streptococcus pyogenes (Group A Streptococcus, GAS) causes infections from mild pharyngitis to severe septic infections. Acute kidney injury (AKI) is a condition of prompt decline of renal function. The aim of the present study was to report the incidence and outcome of AKI in GAS bacteraemia and to evaluate the diagnostic value of serum C-reactive protein as an indicator of AKI. METHODS: All adult patients with GAS bacteraemia treated at Turku University Hospital from 2007 to 2018 were identified and their patient records were scrutinised. RESULTS: Of 195 included patients, 38 (19.5%) had AKI stage 1, 20 (10.3%) AKI stage 2 and 26 (13.3%) AKI stage 3 and 111 (56.9%) did not have AKI. The adjusted seven-day mortality was significantly higher in AKI stages 2 and 3 compared to the non-AKI group (15% and 19% vs. 3.6%; p = .046 and .006, respectively). Of the survivors, 95.8% met the criteria of renal recovery at discharge. The higher the AKI stage, the higher was the mean serum CRP level on admission. The optimal cut-off for CRP to identify patients with AKI stage 2 or 3 was ≥244 mg/l (sensitivity 82.6% and specificity 75.8%). CONCLUSIONS: AKI is common in patients with GAS bacteraemia and the severity of AKI correlates with the CRP level on admission. The mortality of patients with GAS bacteraemia and AKI is significantly higher than of patients without AKI. Most survivors, however, show renal recovery.Key MessageAKI is common in group A Streptococcal bacteraemia and increases mortality compared to bacteraemia alone. However, renal recovery is also common. A high CRP level on admission correlates significantly positively with the degree of severity of AKI.

Oral Doxycycline Compared to Intravenous Ceftriaxone in the Treatment of Lyme Neuroborreliosis: A Multicenter, Equivalence, Randomized, Open-label Trial.

BACKGROUND: Lyme neuroborreliosis (LNB) is often treated with intravenous ceftriaxone even if doxycycline is suggested to be noninferior to ceftriaxone. We evaluated the efficacy of oral doxycycline in comparison to ceftriaxone in the treatment of LNB. METHODS: Patients with neurological symptoms suggestive of LNB without other obvious reasons were recruited. The inclusion criteria were (1) production of Borrelia burgdorferi-specific antibodies in cerebrospinal fluid (CSF) or serum; (2) B. burgdorferi DNA in the CSF; or (3) an erythema migrans during the past 3 months. Participants were randomized in a 1:1 ratio to receive either oral doxycycline 100 mg twice daily for 4 weeks, or intravenous ceftriaxone 2 g daily for 3 weeks. The participants described their subjective condition with a visual analogue scale (VAS) from 0 to 10 (0 = normal; 10 = worst) before the treatment, and 4 and 12 months after the treatment. The primary outcome was the change in the VAS score at 12 months. RESULTS: Between 14 September 2012 and 28 December 2017, 210 adults with suspected LNB were assigned to receive doxycycline (n = 104) or ceftriaxone (n = 106). The per-protocol analysis comprised 82 patients with doxycycline and 84 patients with ceftriaxone. The mean change in the VAS score was -3.9 in the doxycycline group and -3.8 in the ceftriaxone group (mean difference, 0.17 [95% confidence interval, -.59 to .92], which is within the prespecified equivalence margins of -1 to 1 units). Participants in both groups improved equally. CONCLUSIONS: Oral doxycycline is equally effective as intravenous ceftriaxone in the treatment of LNB. CLINICAL TRIALS REGISTRATION: NCT01635530 and EudraCT 2012-000313-37.

Group A streptococcal bacteremias in Southwest Finland 2007-2018: epidemiology and role of infectious diseases consultation in antibiotic treatment selection.

The incidence of invasive group A streptococcal (GAS) infections has shown a fluctuating but increasing trend in Finland. The impact of infectious diseases specialist consultation (IDSC) on the antimicrobial therapy of GAS bacteremia has not been studied earlier. A retrospective study on adult GAS bacteremia in The Hospital District of Southwest Finland (HDSWF) was conducted from 2007 to 2018. Data on incidence of bacteremic GAS cases were gathered from the National Infectious Disease Register. Clinical data were obtained by reviewing the electronic patient records. The overall incidence of GAS bacteremia in HDSWF was 3.52/100,000, but year-to-year variation was observed with the highest incidence of 7.93/100,000 in 2018. A total of 212 adult GAS bacteremia cases were included. A record of IDSC was found (+) in 117 (55.2%) cases, not found (-) in 71 (33.5%) cases and data were not available in 24 (11.3%) cases. Among IDSC+ cases, 57.3% were on penicillin G treatment whereas in the group IDSC- only 22.5%, respectively (OR = 4.61, 95% CI 2.37-8.97; p < 0.001). The use of clindamycin as adjunctive antibiotic was more common among IDSC+ (54.7%) than IDSC- (21.7%) (OR = 4.51, 95% CI 2.29-8.87; p < 0.001). There was an increasing trend in incidence of GAS bacteremia during the study period. Narrow-spectrum beta-lactam antibiotics were chosen, and adjunctive clindamycin was more commonly used, if IDSC took place. This highlights the importance of availability of IDSC but calls for improved practice among infectious diseases specialists by avoiding combination therapy with clindamycin in non-severe invasive GAS infections.