The consumption of broad-spectrum drugs has increased as a consequence of the spread of multidrug-resistant (MDR) Escherichia coli. Finding alternatives for these infections is critical, for which ...some neglected drugs may be an option.
To determine whether fosfomycin is noninferior to ceftriaxone or meropenem in the targeted treatment of bacteremic urinary tract infections (bUTIs) due to MDR E coli.
This multicenter, randomized, pragmatic, open clinical trial was conducted at 22 Spanish hospitals from June 2014 to December 2018. Eligible participants were adult patients with bacteremic urinary tract infections due to MDR E coli; 161 of 1578 screened patients were randomized and followed up for 60 days. Data were analyzed in May 2021.
Patients were randomized 1 to 1 to receive intravenous fosfomycin disodium at 4 g every 6 hours (70 participants) or a comparator (ceftriaxone or meropenem if resistant; 73 participants) with the option to switch to oral fosfomycin trometamol for the fosfomycin group or an active oral drug or parenteral ertapenem for the comparator group after 4 days.
The primary outcome was clinical and microbiological cure (CMC) 5 to 7 days after finalization of treatment; a noninferiority margin of 7% was considered.
Among 143 patients in the modified intention-to-treat population (median IQR age, 72 62-81 years; 73 51.0% women), 48 of 70 patients (68.6%) treated with fosfomycin and 57 of 73 patients (78.1%) treated with comparators reached CMC (risk difference, -9.4 percentage points; 1-sided 95% CI, -21.5 to ∞ percentage points; P = .10). While clinical or microbiological failure occurred among 10 patients (14.3%) treated with fosfomycin and 14 patients (19.7%) treated with comparators (risk difference, -5.4 percentage points; 1-sided 95% CI, -∞ to 4.9; percentage points; P = .19), an increased rate of adverse event-related discontinuations occurred with fosfomycin vs comparators (6 discontinuations 8.5% vs 0 discontinuations; P = .006). In an exploratory analysis among a subset of 38 patients who underwent rectal colonization studies, patients treated with fosfomycin acquired a new ceftriaxone-resistant or meropenem-resistant gram-negative bacteria at a decreased rate compared with patients treated with comparators (0 of 21 patients vs 4 of 17 patients 23.5%; 1-sided P = .01).
This study found that fosfomycin did not demonstrate noninferiority to comparators as targeted treatment of bUTI from MDR E coli; this was due to an increased rate of adverse event-related discontinuations. This finding suggests that fosfomycin may be considered for selected patients with these infections.
ClinicalTrials.gov Identifier: NCT02142751.
There has been a rapid increase in recent years in the incidence of infection and colonization by carbapenemase-producing Enterobacteriaceae (CPE). A number of clusters and outbreaks have been ...reported, some of which have been contained, providing evidence that these clusters and outbreaks can be managed effectively when the appropriate control measures are implemented. This review outlines strategies recommended to control CPE dissemination both at the healthcare facility level (acute and long-term care) and from the public health point of view. A dedicated prepared plan should be required to prevent the spread of CPE at the hospital level. At the front line, activities should include management of patients at admission and new cases, active surveillance culturing and definition of high-risk groups. High compliance with standard precautions for all patients and full or modified contact precautions for defined categories of patients should be implemented. Long-term care facilities are areas where dissemination can also take place but more importantly they can become a reservoir as patients are admitted and released to other Health care facilities. From the public health point of view, surveillance must be tailored to identify regional spread and interfacility transmission to prevent further dissemination. Finally, a comprehensive set of activities at various levels is necessary to prevent further spread of these bacteria in the community.
Summary Objective To determine current outcomes and predictors of treatment failure among patients with surgical site infection (SSI) after colorectal surgery. Methods A multicentre observational ...prospective cohort study of adults undergoing elective colorectal surgery in 10 Spanish hospitals (2011–2014). Treatment failure was defined as persistence of signs/symptoms of SSI or death at 30 days post-surgery. Results Of 3701 patients, 669 (18.1%) developed SSI; 336 (9.1%) were organ-space infections. Among patients with organ-space SSI, 81.2% required source control: 60.4% reoperation and 20.8% percutaneous/transrectal drainage. Overall treatment failure rate was 21.7%: 9% in incisional SSIs and 34.2% in organ-space SSIs ( p < 0.001). Median length of stay was 15 days (IQR 9–22) for incisional SSIs and 24 days (IQR 17–35) for organ-space SSIs ( p < 0.001). One hundred and twenty-seven patients (19%) required readmission and 35 patients died (5.2%). Risk factors for treatment failure among patients with organ-space SSI were age ≥65 years (OR 1.83, 95% CI: 1.07–1.83), laparoscopy (OR 1.7, 95% CI: 1.06–2.77), and reoperation (OR 2.8, 95% CI: 1.7–4.6). Conclusions Rates of SSI and treatment failure in organ-space SSI after elective colorectal surgery are notably high. Careful attention should be paid to older patients with previous laparoscopy requiring reoperation for organ-space SSI, so that treatment failure can be identified early.
Background and Objectives
Morbidity and mortality from serious infections are common in intensive care units (ICUs). The appropriateness of the antibiotic treatment is essential to combat sepsis. We ...aimed to evaluate pharmacokinetic/pharmacodynamic target attainment of meropenem and piperacillin/tazobactam administered at standard total daily dose as continuous infusion in critically ill patients without renal dysfunction and to identify risk factors of non-pharmacokinetic/pharmacodynamic target attainment.
Results
We included 118 patients (149 concentrations), 47% had microorganism isolation. Minimum inhibitory concentration (MIC) median (interquartile range, IQR) values in isolated pathogens were: meropenem: 0.05 (0.02–0.12) mg/l; piperacillin: 3 (1–4) mg/l. Pharmacokinetic/pharmacodynamic target attainments (100%
f
C
ss≥1xMIC
, 100%
f
C
ss≥4xMIC
and 100%
f
C
ss ≥ 8xMIC
, respectively) were: 100%, 96.15%, 96.15% (meropenem) and 95.56%, 91.11%, 62.22% (piperacillin) for actual MIC; 98.11%, 71.70%, 47.17% (meropenem, MIC 2 mg/l), 95.83%, 44.79%, 6.25% (piperacillin, MIC 8 mg/l), 83.33%, 6.25%, 1.04% (piperacillin, MIC 16 mg/l) for EUCAST breakpoint of
Enterobacteriaceae
spp. and
Pseudomonas
spp. Multivariable linear analysis identified creatinine clearance (CrCL) as a predictive factor of free antibiotic concentrations (
f
C
ss
) of both therapies (meropenem
β
= − 0.01 (95% CI − 0.02 to − 0.0;
p
= 0.043) and piperacillin
β
= − 0.01 (95% CI − 0.02 to 0.01,
p
< 0.001)). Neurocritical status was associated with lower piperacillin
f
C
ss
β
= − 0.36 (95% CI − 0.61 to − 0.11;
p
= 0.005).
Conclusion
Standard total daily dose of meropenem allowed achieving pharmacokinetic/pharmacodynamic target attainments in ICU patients without renal dysfunction. Higher doses of piperacillin/tazobactam would be needed to cover microorganisms with MIC > 8 mg/l. CrCL was the most powerful factor predictive of
f
C
ss
in both therapies.
Data on risk factors for carbapenem-resistant Enterobacterales (CRE) with wider applicability are needed to inform preventive measures and efficient design of randomised trials.
An international ...matched case-control-control study was performed in 50 hospitals with high CRE incidence from March 2016 to November 2018 to investigate different aspects of infections caused by CRE (NCT02709408). Cases were patients with complicated urinary tract infection (cUTI), complicated intraabdominal (cIAI), pneumonia or bacteraemia from other sources (BSI-OS) due to CRE; control groups were patients with infection caused by carbapenem-susceptible Enterobacterales (CSE), and by non-infected patients, respectively. Matching criteria included type of infection for CSE group, ward and duration of hospital admission. Conditional logistic regression was used to identify risk factors.
Overall, 235 CRE case patients, 235 CSE controls and 705 non-infected controls were included. The CRE infections were cUTI (133, 56.7%), pneumonia (44, 18.7%), cIAI and BSI-OS (29, 12.3% each). Carbapenemase genes were found in 228 isolates: OXA-48/like, 112 (47.6%), KPC, 84 (35.7%), and metallo-β-lactamases, 44 (18.7%); 13 produced two. The risk factors for CRE infection in both type of controls were (adjusted OR for CSE controls; 95% CI; p value) previous colonisation/infection by CRE (6.94; 2.74–15.53; <0.001), urinary catheter (1.78; 1.03–3.07; 0.038) and exposure to broad spectrum antibiotics, as categorical (2.20; 1.25–3.88; 0.006) and time-dependent (1.04 per day; 1.00–1.07; 0.014); chronic renal failure (2.81; 1.40–5.64; 0.004) and admission from home (0.44; 0.23–0.85; 0.014) were significant only for CSE controls. Subgroup analyses provided similar results.
The main risk factors for CRE infections in hospitals with high incidence included previous colonization, urinary catheter and exposure to broad spectrum antibiotics.
The study was funded by the Innovative Medicines Initiative Joint Undertaking (https://www.imi.europa.eu/) under Grant Agreement No. 115620 (COMBACTE-CARE).
Carbapenem-resistant Acinetobacter baumannii (CRAb) is a major source of nosocomial infections in Spain associated with the production of OXA-58-like or OXA-24/40-like β-lactamase enzymes. We ...analysed the plasmids carrying the bla(OXA-24/40)-like gene in CRAb isolates obtained a decade apart.
The presence of β-lactamases was screened for by PCR (metallo-β-lactamases, carbapenem-hydrolysing class D β-lactamases, GES and KPC) in 101 CRAb isolates obtained in two multicentre studies (GEIH/REIPI-Ab-2000 and GEIH/REIPI-Ab-2010; n = 493 Acinetobacter spp). We analysed the distribution and characterization of the plasmids carrying the bla(OXA-24/40)-like gene and sequenced two plasmids, AbATCC223p (2000) and AbATCC329p (2010) from A. baumannii ATCC 17978 transformants.
Acquisition of the bla(OXA-24/40)-like gene was the main mechanism underlying resistance to carbapenems (48.7% in 2000 compared with 51.6% in 2010). This gene was mainly isolated in ST2 A. baumannii strains in both studies, although some novel STs (ST79 and ST80) appeared in 2010. The gene was located in plasmids (8-12 kbp) associated with the repAci2 or repAci2/repGR12 types. The sequences of AbATCC223p (8840 bp) and AbATCC329p (8842 bp) plasmids were similar, particularly regarding the presence of the genes encoding the AbkA/AbkB proteins associated with the toxin/antitoxin system. Moreover, the abkA/abkB gene sequences (>96% identity) were also located in plasmids harbouring the bla(OXA-58)-like gene.
The action of OXA-24/40 and OXA-58 β-lactamase-like enzymes represents the main mechanism underlying resistance to carbapenems in Spain in the last decade. AbkA/AbkB proteins in the toxin/antitoxin system may be involved in the successful dissemination of plasmids carrying the bla(OXA-24/40)-like gene, and probably also the bla(OXA-58)-like gene, thus contributing to the plasmid stability.
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