Efficacy and safety of colistin plus beta-lactams for bone and joint infection caused by fluoroquinolone-resistant gram-negative bacilli: a prospective multicenter study.

OBJECTIVES: The prognosis of bone and joint infections (BJI) caused by Gram-negative bacilli (GNB) worsens significantly in the face of fluoroquinolone-resistance. In this setting, scarce pre-clinical and clinical reports suggest that intravenous beta-lactams plus colistin may improve outcome. Our aim was to assess the efficacy and safety of this treatment in a well-characterized prospective cohort. METHODS: Observational, prospective, non-comparative, multicenter (14 hospitals) study of adults with BJI caused by fluoroquinolone-resistant GNB treated with surgery and intravenous beta-lactams plus colistin for ≥ 21 days. The primary endpoint was the cure rate. RESULTS: Of the 44 cases included (median age 72 years [IQR 50-81], 22 [50%] women), 32 (73%) had an orthopedic device-related infection, including 17 (39%) prosthetic joints. Enterobacterales were responsible for 27 (61%) episodes, and Pseudomonas spp for 17 (39%), with an overall rate of MDR/XDR GNB infections of 27/44 (61%). Patients were treated with colistin plus intravenous beta-lactam for 28 days (IQR 22-37), followed by intravenous beta-lactam alone for 19 days (IQR 5-35). The cure rate (intention-to-treat analysis; median follow-up = 24 months, IQR 19-30) was 82% (95% CI 68%-90%) and particularly, 80% (95% CI 55%-93%) among patients managed with implant retention. Adverse events (AEs) leading to antimicrobial withdrawal occurred in 10 (23%) cases, all of which were reversible. Colistin AEs were associated with higher plasma drug concentrations (2.8 mg/L vs. 0.9 mg/L, p = 0.0001). CONCLUSIONS: Combination therapy with intravenous beta-lactams plus colistin is an effective regimen for BJI caused by fluoroquinolone-resistant GNB. AEs were reversible and potentially preventable by close therapeutic drug monitoring.

How can we optimize the diagnostic and therapeutic approach to pneumonia? Expert opinion-based recommendations.

Pneumonia continues to be one of the most frequent infectious syndromes and a relevant cause of death and health resources utilization. The OPENIN ("Optimización de procesos clínicos para el diagnóstico y tratamiento de infecciones") Group is composed of Infectious Diseases specialists and Microbiologists and aims at generating recommendations that can contribute to improve the approach to processes with high impact on the health system. Such task relies on a critical review of the available scientific evidence. The first Group meeting (held in October 2023) aimed at answering the following questions: Can we optimize the syndromic and microbiological diagnosis of pneumonia? Is it feasible to safely shorten the length of antibiotic therapy? And, is there any role for the immunomodulatory strategies based on the adjuvant use of steroids, macrolides or immunoglobulins? The present review summarizes the literature reviewed for that meeting and offers a series of expert recommendations.

Is advanced age still a risk factor for recurrence of C. difficile infection in the era of new treatments?

BACKGROUND: Advanced age has been widely identified as a risk factor for recurrent Clostridioides difficile infection (CDI), but most related studies were performed before the introduction of novel therapies. The aim of this study was to compare CDI characteristics and outcomes in patients over and under 80 years old with CDI and their outcomes in the era of new treatments. METHODS: This was a retrospective cohort study of patients diagnosed with CDI from January 2021 to December 2022 in an academic hospital. We compared recurrence and mortality at 12 weeks after the end of treatment. An extension of the Fine and Grey model adjusted for competing events was used to assess the effect of age on recurrence. RESULTS: Four hundred seventy-six patients were considered to have CDI (320 in patients <80 years and 156 in ≥80 years). CDI in older patients was more frequently healthcare-associated and was more severe. Although the Charlson index was almost identical between populations, comorbidities clearly differed. New treatments (bezlotoxumab, fidaxomicin and faecal microbiota transplantation) were more frequently used in older patients without statistical significance (41.3% vs. 33.4%, P = .053). There were 69 (14.5%) recurrences, with no differences by age group after adjusting for competing events. Mortality was greater in the oldest (35.3%) than in the youngest (13.1%); P < .001. CONCLUSIONS: No differences in CDI recurrence rates were found between age groups. However, there was a high mortality rate in patients ≥80 years old, which emphasises the urgent need to improve the prevention and treatment of CDI in this group.

Impact of an Intervention Program on Clostridioides difficile Infections: Comparison of 2 Hospital Cohorts.

Background: Clostridioides difficile infection (CDI) occurs in various contexts and care settings and is managed by multiple specialists who are not experts in its management. While there are many initiatives to improve the diagnosis and avoid overdiagnosis, there is less focus on the overall management of the infection. Methods: We studied a cohort of patients with a positive test result for toxigenic C difficile in 2 hospitals. Hospital A has a program that provides advice from an infectious disease specialist (IDS) and promotes continuity of care by providing a phone number to contact the IDS. Hospital B does not have any specific CDI program. The evaluation assessed the proportion of patients not treated (carriers or self-limited disease), adherence to Infectious Diseases Society of America guidelines, access to novel therapies, recurrence and mortality rates, and readmission and emergency department visits due to CDI. We assessed the program's effectiveness through a logistic regression model adjusted for covariates chosen by clinical criteria. Results: Hospital A avoided more unnecessary treatments (19.3% vs 11.5%), provided access to novel therapies more frequently (35.3% vs 13%), and adhered more closely to current guidelines (95.8% vs 71.3%). Although the mortality and recurrence rates did not differ, the absence of an intervention program was associated with greater odds of admission due to recurrence (odds ratio, 4.19; P = .037) and more visits to the emergency department due to CDI (odds ratio, 8.74; P = .001). Conclusions: Implementation of a CDI intervention program based on recommendations from IDSs and improved access to specialized care during the follow-up is associated with enhanced quality of CDI management and potential reductions in hospital resource utilization.

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.

Executive summary: Guidelines for the diagnosis and treatment of septic arthritis in adults and children, developed by the GEIO (SEIMC), SEIP and SECOT.

Infection of a native joint, commonly referred to as septic arthritis, is a medical emergency because of the risk of joint destruction and subsequent sequelae. Its diagnosis requires a high level of suspicion. These guidelines for the diagnosis and treatment of septic arthritis in children and adults are intended for use by any physician caring for patients with suspected or confirmed septic arthritis. They have been developed by a multidisciplinary panel with representatives from the Bone and Joint Infections Study Group (GEIO) belonging to the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), the Spanish Society of Paediatric Infections (SEIP) and the Spanish Society of Orthopaedic Surgery and Traumatology (SECOT), and two rheumatologists. The recommendations are based on evidence derived from a systematic literature review and, failing that, on the opinion of the experts who prepared these guidelines. A detailed description of the background, methods, summary of evidence, the rationale supporting each recommendation, and gaps in knowledge can be found online in the complete document.

First detection in Spain of NDM-1-producing Pseudomonas aeruginosa in two patients transferred from Ukraine to a university hospital.

OBJECTIVES: Carbapenemase-mediated carbapenem resistance in Pseudomonas aeruginosa is a relevant health problem. We detected for the first time in Spain two clinical NDM-producing P. aeruginosa (NDM-Pa) isolates in two Ukrainian patients admitted to our hospital between April and August 2022. METHODS: Antimicrobial susceptibility was studied by microdilution and MIC gradient strips (EUCAST-2022 criteria). Carbapenemase genes were detected by the Xpert Carba-R and immunochromatography assays. WGS (Illumina and Oxford-Nanopore) was also performed. RESULTS: In May 2022, we detected an NDM-Pa in a sternotomy wound in a patient. In June-2022, a second NDM-Pa along with an OXA-48-Klebsiella pneumoniae (OXA-48-Kp) isolate was detected in a mandibular abscess from an unrelated patient. Moreover, an NDM+OXA-48-K. pneumoniae (NDM+OXA-48-Kp) was also found in a rectal sample of this patient. Both patients had undergone surgery in Ukraine before their transfer to our hospital. NDM-Pa isolates were resistant to all tested antimicrobials with the exception of aztreonam (MIC = 8 mg/L), colistin (MIC =2 mg/L) and cefiderocol (MIC range = 0.75-2 mg/L). WGS confirmed that both P. aeruginosa isolates were NDM-1 producers, belonged to ST773 and shared an identical resistome. blaNDM-1 was located on a ∼117-Kb chromosomally integrated integrative conjugative element (ICE). OXA-48-Kp and NDM+OXA-48-Kp belonged to ST147 and contained blaOXA-48 on an identical ∼300-Kb IncHIB-plasmid. blaNDM-1 was located on a 51-Kb IncFIB-plasmid only found in NDM+OXA-48-Kp. CONCLUSIONS: This is the first description of NDM-Pa in Spain. We highlight the threat of further cross-border dissemination of NDM-1 through P. aeruginosa along with K. pneumoniae high-risk clones also carrying OXA-48, which draws a complex epidemiological scenario.

Conventional versus extended-pulsed fidaxomicin dosing in patients at high risk of recurrence of Clostridioides difficile infection: a propensity score analysis.

INTRODUCTION: The main challenge in the treatment of Clostridioides difficile infection (CDI) is to reduce recurrence rates. Fidaxomicin improves the recurrence rate of CDI compared with vancomycin. Extended-pulsed dosing of fidaxomicin was associated with lower recurrence rates in one clinical trial but has never been directly compared with conventional fidaxomicin dosing. METHODS: To compare the recurrence rate of fidaxomicin conventional dosing (FCD) and fidaxomicin in extended-pulsed dosing (FEPD) in conditions of clinical practice at a single institution. We performed propensity score matching taking the variables age, severity and previous episode as confounders to evaluate patients with a similar recurrence risk. RESULTS: In total, 254 episodes of CDI treated with fidaxomicin were evaluated: 170 (66.9%) received FCD, and 84 (33.1%) received FEPD. More patients who received FCD were hospitalized for CDI, had severe CDI and had a diagnosis based on toxin detection. In contrast, the proportion of patients receiving proton pump inhibitors was higher in those receiving FEPD. The crude recurrence rates in FCD- and FEPD-treated patients were 20.0% and 10.7%, respectively (OR:0.48; 95% CI 0.22-1.05; P = 0.068). We did not find any differences in CDI recurrence rate in patients receiving FEPD versus FCD (OR = 0.74; 95% CI 0.27-2.04) by propensity score analysis. CONCLUSIONS: Although the recurrence rate with FEPD was numerically lower than that observed with FCD, we have not been able to show that the recurrence rate of CDI is different depending on the dosage regimen of fidaxomicin. Clinical trials or large observational studies comparing the two dosing regimens of fidaxomicin are needed.

Carbapenemase-producing Enterobacterales infections in COVID-19 patients.

BACKGROUND: Carbapenemase-producing Enterobacterales (CPE) infections have been occasionally described in patients with coronavirus disease-19 (COVID-19). We assess the clinical features and outcome of these infections. METHODS: In this retrospective single-centre, case-control study, we included 54 patients with CPE infection: 30 case-patients (COVID-19) and 24 controls (non-COVID-19), collected between March and May 2020. We compared the epidemiological, clinical features, and outcome between cases and controls. RESULTS: CPE infection was more frequent in COVID-19 patients than in controls (1.1 vs. 0.5%, p = .005). COVID-19 patients were younger, had a lower frequency of underlying diseases (p = .01), and a lower median Charlson score (p = .002). Predisposing factors such as antimicrobial use, mechanical ventilation, or ICU admission, were more frequent in COVID-19 patients (p < .05). There were 73 episodes of infection (42 cases and 31 controls) that were more frequently hospital-acquired and diagnosed at the ICU in COVID-19 patients (p < .001). Urinary tract was the most common source of infection (47.9%), followed by pneumonia (23.3%). The frequency of severe sepsis or shock (p = .01) as well as the median SOFA score (p = .04) was higher in cases than in controls. Klebsiella pneumoniae (80.8%), Serratia marcescens (11%) and Enterobacter cloacae (4.1%) were the most common bacteria in both groups (KPC 56.2%, OXA-48 26% and VIM 17.8%). Overall 30-d mortality rate of COVID-19 patients and controls was 30 and 16.7%, respectively (p = .25). CONCLUSIONS: COVID-19 patients have an increased risk of CPE infections, which usually present as severe, nosocomial infections, appearing in critically-ill patients and associated with a high mortality.

The efficacy of suppressive antibiotic treatment in patients managed non-operatively for periprosthetic joint infection and a draining sinus.

Objectives: Patients with prosthetic joint infections (PJIs) not suitable for curative surgery may benefit from suppressive antibiotic therapy (SAT). However, the usefulness of SAT in cases with a draining sinus has never been investigated. Methods: A multicentre, retrospective observational cohort study was performed in which patients with a PJI and a sinus tract were eligible for inclusion if managed conservatively and if sufficient follow-up data were available (i.e. at least 2 years). SAT was defined as a period of >  6 months of oral antibiotic therapy. Results: SAT was initiated in 63 of 72 (87.5 %) included patients. Implant retention during follow-up was the same in patients receiving SAT vs. no SAT (79.4 % vs. 88.9 %; p = 0 .68). In total, 27 % of patients using SAT experienced side effects. In addition, the occurrence of prosthetic loosening in initially fixed implants, the need for surgical debridement, or the occurrence of bacteremia during follow-up could not be fully prevented with the use of SAT, which still occurred in 42 %, 6.3 %, and 3.2 % of cases, respectively. However, the sinus tract tended to close more often (42 % vs. 13 %; p = 0 .14), and a higher resolution of pain was observed (35 % vs. 14 %; p = 0 .22) in patients receiving SAT. Conclusions: SAT is not able to fully prevent complications in patients with a draining sinus. However, it may be beneficial in a subset of patients, particularly in those with pain or the hindrance of a draining sinus. A future prospective study, including a higher number of patients not receiving SAT, is needed.

Suppressive Antibiotic Treatment in Prosthetic Joint Infections: A Perspective.

The treatment of prosthetic joint infections (PJIs) is a complex matter in which surgical, microbiological and pharmacological aspects must be integrated and, above all, placed in the context of each patient to make the best decision. Sometimes it is not possible to offer curative treatment of the infection, and in other cases, the probability that the surgery performed will be successful is considered very low. Therefore, indefinite administration of antibiotics with the intention of "suppressing" the course of the infection becomes useful. For decades, we had little information about suppressive antibiotic treatment (SAT). However, due to the longer life expectancy and increase in orthopaedic surgeries, an increasing number of patients with infected joint prostheses experience complex situations in which SAT should be considered as an alternative. In the last 5 years, several studies attempting to answer the many questions that arise on this issue have been published. The aim of this publication is to review the latest published evidence on SAT.

Usefulness of Fecal Calprotectin in the Management of Patients with Toxigenic Clostridioides difficile.

The availability of highly sensitive molecular tests for the detection of Clostridioides difficile in feces leads to overtreatment of patients who are probably only colonized. In this prospective study, the usefulness of fecal calprotectin (fCP) is evaluated in a cohort of patients with detection of toxigenic C. difficile in feces. Patients were classified by an infectious diseases consultant blinded to fCP results into three groups-group I, presumed Clostridioides difficile infection (CDI); group II, doubtful but treated CDI; and group III, presumed C. difficile colonization or self-limited CDI not needing treatment. One hundred and thirty-four patients were included. The median fCP concentrations were 410 (138-815) µg/g in group I, 188 (57-524) µg/g in group II, and 51 (26-97) µg/g in group III (26 cases); p < 0.05 for all comparisons. In forty-five out of 134 cases (33.5%), the fCP concentrations were below 100 µg/g. In conclusion, fCP is low in most patients who do not need treatment against C. difficile, and should be investigated as a potentially useful test in the management of patients with detected toxigenic C. difficile.

Implant Removal in the Management of Prosthetic Joint Infection by Staphylococcus aureus: Outcome and Predictors of Failure in a Large Retrospective Multicenter Study.

OBJECTIVES: To compare the characteristics and outcomes of cases with acute prosthetic joint infection (PJI; early post-surgical or hematogenous) by Staphylococcus aureus managed with implant removal (IRm) or debridement and retention (DAIR). To analyze the outcomes of all cases managed with IRm (initially or after DAIR failure). METHODS: Retrospective, multicenter, cohort study of PJI by S. aureus (2003-2010). Overall failure included mortality within 60 days since surgery and local failure due to staphylococcal persistence/relapse. RESULTS: 499 cases, 338 initially managed with DAIR, 161 with IRm. Mortality was higher in acute PJI managed initially with IRm compared to DAIR, but not associated with the surgical procedure, after propensity score matching. Underlying conditions, hemiarthroplasty, and methicillin-resistant S. aureus were risk factors for mortality. Finally, 249 cases underwent IRm (88 after DAIR failure); overall failure was 15.6%. Local failure (9.3%) was slightly higher in cases with several comorbidities, but independent of previous DAIR, type of IRm, and rifampin treatment. CONCLUSIONS: In a large multicenter study of S. aureus PJI managed with IRm, failure was low, but mortality significant, especially in cases with acute PJI and underlying conditions, but not associated with the IRm itself. Rifampin efficacy was limited in this setting.

Real-life experience with fidaxomicin in Clostridioides difficile infection: a multicentre cohort study on 244 episodes.

The high cost of fidaxomicin has restricted its use despite the benefit of a lower Clostridioides difficile infection (CDI) recurrence rate at 4 weeks of follow-up. This short follow-up represents the main limitation of pivotal clinical trials of fidaxomicin, and some recent studies question its benefits over vancomycin. Moreover, the main risk factors of recurrence after treatment with fidaxomicin remain unknown. We designed a multicentre retrospective cohort study among four Spanish hospitals to assess the efficacy of fidaxomicin in real life and to investigate risk factors of fidaxomicin failure at weeks 8 and 12. Two-hundred forty-four patients were included. Fidaxomicin was used in 96 patients (39.3%) for a first episode of CDI, in 95 patients (38.9%) for a second episode, and in 53 patients (21.7%) for a third or subsequent episode. Patients treated with fidaxomicin in a first episode were younger (59.9 years vs 73.5 years), but they had more severe episodes (52.1% vs. 32.4%). The recurrence rates for patients treated in the first episode were 6.5% and 9.7% at weeks 8 and 12, respectively. Recurrence rates increased for patients treated at second or ulterior episodes (16.3% and 26.4% at week 8, respectively). Age greater than or equal to 85 years and having had a previous episode of CDI were identified as recurrence risk factors at weeks 8 and 12. We conclude that the outcomes with fidaxomicin in real life are at least as good as those observed in clinical trials despite a more demanding evaluation. Be it 85 years of age or older, and the use after a first episode appears to be independent factors of CDI recurrence after treatment with fidaxomicin.

Infections after spine instrumentation: effectiveness of short antibiotic treatment in a large multicentre cohort.

BACKGROUND AND OBJECTIVES: Available information about infection after spine instrumentation (IASI) and its management are scarce. We aimed to analyse DAIR (debridement, antibiotics and implant retention) prognosis and evaluate effectiveness of short antibiotic courses on early forms. METHODS: Multicentre retrospective study of patients with IASI managed surgically (January 2010-December 2016). Risk factors for failure were analysed by multivariate Cox regression and differences between short and long antibiotic treatment were evaluated with a propensity score-matched analysis. RESULTS: Of the 411 IASI cases, 300 (73%) presented in the first month after surgery, 48 in the second month, 22 in the third and 41 thereafter. Infections within the first 2 months (early cases) occurred mainly to older patients, with local inflammatory signs and predominance of Enterobacteriaceae, unlike those in the later periods. When managed with DAIR, prognosis of early cases was better than later ones (failure rate 10.4% versus 26.1%, respectively; P = 0.02). Risk factors for DAIR failure in early cases were female sex, Charlson Score, large fusions (>6 levels) and polymicrobial infections (adjusted HRs of 2.4, 1.3, 2.6 and 2.26, respectively). Propensity score matching proved shorter courses of antibiotics (4-6 weeks) as effective as longer courses (failure rates 11.4% and 10.5%, respectively; P = 0.870). CONCLUSIONS: IASIs within the first 2 months could be managed effectively with DAIR and shorter antibiotic courses. Clinicians should be cautious when faced with patients with comorbidities, large fusions and/or polymicrobial infections.

Impact of the coronavirus disease 2019 (COVID-19) pandemic on nosocomial Clostridioides difficile infection.

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has induced a reinforcement of infection control measures in the hospital setting. Here, we assess the impact of the COVID-19 pandemic on the incidence of nosocomial Clostridioides difficile infection (CDI). METHODS: We retrospectively compared the incidence density (cases per 10,000 patient days) of healthcare-facility-associated (HCFA) CDI in a tertiary-care hospital in Madrid, Spain, during the maximum incidence of COVID-19 (March 11 to May 11, 2020) with the same period of the previous year (control period). We also assessed the aggregate in-hospital antibiotic use (ie, defined daily doses [DDD] per 100 occupied bed days [BD]) and incidence density (ie, movements per 1,000 patient days) of patient mobility during both periods. RESULTS: In total, 2,337 patients with reverse transcription-polymerase chain reaction-confirmed COVID-19 were admitted to the hospital during the COVID-19 period. Also, 12 HCFA CDI cases were reported at this time (incidence density, 2.68 per 10,000 patient days), whereas 34 HCFA CDI cases were identified during the control period (incidence density, 8.54 per 10,000 patient days) (P = .000257). Antibiotic consumption was slightly higher during the COVID-19 period (89.73 DDD per 100 BD) than during the control period (79.16 DDD per 100 BD). The incidence density of patient movements was 587.61 per 1,000 patient days during the control period and was significantly lower during the COVID-19 period (300.86 per 1,000 patient days) (P < .0001). CONCLUSIONS: The observed reduction of ~70% in the incidence density of HCFA CDI in a context of no reduction in antibiotic use supports the importance of reducing nosocomial transmission by healthcare workers and asymptomatic colonized patients, reinforcing cleaning procedures and reducing patient mobility in the epidemiological control of CDI.

Chronic prosthetic joint infections with a draining sinus. Who should receive suppressive antibiotic treatment?

The benefit of suppressive antibiotic treatment in inoperable patients with a chronic periprosthetic joint infection and a sinus tract is unknown. Some physicians prefer to just let the sinus drain, while others prefer antibiotic treatment. In this viewpoint article we discuss the advantages and disadvantages of suppressive antibiotic treatment in this particular patient group.

Long-Term Impact of Suppressive Antibiotic Therapy on Intestinal Microbiota.

The aim was to describe the safety of indefinite administration of antibiotics, the so-called suppressive antibiotic therapy (SAT) and to provide insight into their impact on gut microbiota. 17 patients with SAT were recruited, providing a fecal sample. Bacterial composition was determined by 16S rDNA massive sequencing, and their viability was explored by PCR-DGGE with and without propidium monoazide. Presence of antibiotic multirresistant bacteria was explored through the culture of feces in selective media. High intra-individual variability in the genera distribution regardless of the antibiotic or antibiotic administration ingestion period, with few statistically significant differences detected by Bray-Curtis distance-based principle component analysis, permutational multivariate analysis of variance and linear discriminant analysis effect size analysis. However, the microbiota composition of patients treated with both beta-lactams and sulfonamides clustered by a heat map. Curiously, the detection of antibiotic resistant bacteria was almost anecdotic and CTX-M-15-producing E. coli were detected in two subjects. Our work demonstrates the overall clinical safety of SAT and the low rate of the selection of multidrug-resistant bacteria triggered by this therapy. We also describe the composition of intestinal microbiota under the indefinite use of antibiotics for the first time.