•88% of Enterobacterales resistant to 3GC remained susceptible to ceftolozane-tazobactam.•Susceptibility to ceftolozane-tazobactam varies from 93% to only 13% for CTX-M and SHV-ESBL producers.•95.6% ...of Enterobacterales responsible for infections remained susceptible to ceftolozane-tazobactam.•Despite 99% CA, Etest® led to an underestimation of the ceftolozane-tazobactam MIC .
Ceftolozane-tazobactam (C/T) proved its efficacy for the treatment of infections caused by non-carbapenemase producing Pseudomonas aeruginosa and Enterobacterales. Here, we aimed to provide susceptibility data on a large series of Enterobacterales since the revision of EUCAST categorization breakpoints in 2020.
First, C/T susceptibility was determined on characterized Enterobacterales resistant to third generation cephalosporins (3GCs) (extended spectrum β-lactamase ESBL production or different levels of AmpC overexpression) (n = 213) and carbapenem-resistant Enterobacterales (CRE) (n = 259), including 170 carbapenemase producers (CPE). Then, 1632 consecutive clinical Enterobacterales responsible for infection were prospectively collected in 23 French hospitals. C/T susceptibility was determined by E-test® (biomérieux) and broth microdilution (BMD) (Sensititre™, Thermo Scientific) to perform method comparison.
Within the collection isolates, 88% of 3GC resistant strains were susceptible to C/T, with important variation depending on the resistance mechanism: 93% vs. 13% susceptibility for CTX-M and SHV-ESBL producers, respectively. Only 20% of the CRE were susceptible to C/T. Among CPE, 80% of OXA-48-like producers were susceptible to C/T, whereas all metallo-β-lactamase producers were resistant. The prospective study revealed that 95.6% of clinical isolates were susceptible to C/T. Method comparison performed on these 1632 clinical isolates demonstrated 99% of categorization agreement between MIC to C/T determined by E-test® in comparison with the BMD (reference) and only 74% of essential agreement.
Overall, C/T showed good activity against wild-type Enterobacterales, AmpC producers, and ESBL-producing Escherichia coli but is less active against ESBL-producing Klebsiella pneumoniae, and CRE. E-test® led to an underestimation of the MICs in comparison to the BMD reference.
Background
Pneumonia is one of the major complications of drowning, but the optimal empirical antibiotic treatment is not clearly defined. Multidrug-resistant (MDR) bacteria and fungi have been ...identified in a recent series of freshwater drowning-associated pneumonia. However, microbial data in seawater drowning are scarce. The objective of the study is to describe the microorganisms isolated in early respiratory specimens obtained from seawater drowning-associated pneumonia and to provide their antibiotic susceptibility pattern.
Methods
All patients admitted for seawater drowning between 2003 and 2013 to two intensive care units, from the region in France with the highest drowning rate, were retrospectively included. Demographics, antimicrobial therapy and microbiological data from respiratory samples collected within the first 48 h after admittance were analyzed.
Results
Seventy-four drowned patients were included, of which 36 (49%) were diagnosed by the clinician as having early pneumonia. Concerning the overall population, the median simplified acute physiology score (version 2) was 45 (30–65), and the mortality was 26%. Twenty-four respiratory samples from different patients were obtained within the first 48 h. Sixteen were positive. The main microorganisms found were
Enterobacteriaceae
(
Enterobacter
spp.,
Klebsiella
spp. and
Escherichia coli
) and Gram-positive aerobic cocci (
Streptococcus pneumonia
and
Staphylococcus aureus)
with a low rate of antimicrobial resistance. No MDR bacteria or fungi were identified. However, among the positive respiratory samples collected, 5/16 (31%) grew bacteria with natural resistance to amoxicillin–clavulanate, the first-line antibiotic commonly used in our cohort. Resistance was only found among Gram-negative bacteria and from respiratory samples of patients with a higher drowning grade at admission (
p
= 0.01).
Conclusions
This 10-year descriptive study, the largest cohort to date, provides early respiratory samples from seawater drowning patients. The microorganisms retrieved were either mostly part of the human oro-pharyngeal flora or
Enterobacteriaceae
and displayed low rates of antimicrobial resistance. Respiratory samples should nonetheless be collected at admittance to the ICU to avoid inappropriate treatment. Empiric use of cephalosporin could be restricted to severe patients or if Gram-negative bacilli are found after direct examination.
We report the case of a 55-year-old man who exhibited a nodular pneumonia 4 months after an allogeneic hematopoietic stem cell transplantation. Culture of the bronchoalveolar lavage fluid revealed ...Nocardia pseudobrasiliensis. This recently described carbapenem-resistant species should be included in the differential diagnosis of fungal infection in this setting.
Matrix-assisted laser desorption ionization-time of flight mass spectrometry is not widely used to identify bacteria directly from positive blood culture bottles (BCBs) because of overlong protocols. ...The objective of this work was to develop and evaluate a simple extraction protocol for reliable identification from BCBs. The 10-min protocol was applied over a 5-month period. Direct identifications on day 0 were compared with those obtained from colonies on day 1 log(score) of ≥2. We evaluated a range of seven log(score) thresholds on day 0 from 1.4 to 2.0 to find the lower confidence score that provides the higher percentage of direct identifications without loss of accuracy. With a log(score) threshold of ≥1.5 at day 0, our protocol allowed us to identify 80% of bacteria in 632 BCBs (96% of
, 95% of
, 92% of enterococci, and 62% of streptococci). At least one bacterial species of the mixture was identified in 77% of the polymicrobial samples. The rapidity and reliability of the protocol were factors in its adoption for routine use, allowing us to save up to 24 h in identifying 80% of the bacteria in the BCBs and, thus, to supply useful information to adapt antibiotic therapy when necessary. We currently provide reliable daily direct identifications of staphylococci, enterococci,
,
and beta-hemolytic streptococci.
Abstract
Background
Current guidelines and literature support the use of therapeutic drug monitoring (TDM) to optimize β-lactam treatment in adult ICU patients.
Objectives
To describe the current ...practice of β-lactam monitoring in French ICUs.
Methods
A nationwide cross-sectional survey was conducted from February 2021 to July 2021 utilizing an online questionnaire that was sent as an email link to ICU specialists (one questionnaire per ICU).
Results
Overall, 119 of 221 (53.8%) French ICUs participated. Eighty-seven (75%) respondents reported having access to β-lactam TDM, including 52 (59.8%) with on-site access. β-Lactam concentrations were available in 24–48 h and after 48 h for 36 (41.4%) and 26 (29.9%) respondents, respectively. Most respondents (n = 61; 70.1%) reported not knowing whether the β-lactam concentrations in the TDM results were expressed as unbound fractions or total concentrations. The 100% unbound fraction of the β-lactam above the MIC was the most frequent pharmacokinetic and pharmacodynamic target used (n = 62; 73.0%).
Conclusions
Despite the publication of international guidelines, β-lactam TDM is not optimally used in French ICUs. The two major barriers are β-lactam TDM interpretation and the required time for results.
Diagnostic uncertainty is common in the emergency room and multidrug-resistant bacteria emerge in the community setting, implying to establish the most efficient empirical antibiotic therapy (eEAT). ...Our aim was to identify such eEAT, considering that in case of DU with severe clinical presentation, most prescribers would propose an empiric combination (EC). The medical dashboard of our ward records prospectively 28 characteristics of each hospitalization including hospitalization motive, final diagnosis, and all antibiotics prescribed. All patients with community-acquired bacteremia (CAB) were included. DU was defined by a discrepancy between suspected diagnosis in the emergency room and final diagnosis. eEAT was defined by in vitro activity of at least one prescribed compound. Finally, independently from the dashboard, we retrospectively compared 2 CTs: amoxicillin/clavulanic acid (AMC)+gentamicin (G) and cefotaxime (3GC)+G. One thousand thirty-four patients with a final diagnosis of CAB were identified from July 2005 to June 2018, including 357 DU (35%) at baseline. eEAT (
n
= 553) was associated with a trend towards a lower death rate compared to inefficient therapies: 5.4 vs 10.0% (
p
= 0.053), and effective antibiotic reassessment was the most protective factor against an unfavorable outcome: 0.34 (0.16–0.71). Bacteria involved in case of UD were resistant to AMC+G and to 3GC+G in 8.1% and 12.8% of patients, respectively. Diagnostic uncertainty was a frequent event requiring antibiotic reassessment. As the latter was not systematically realized, the best eEAT is required and AMC+aminoglycoside should be considered.
•Cephalosporinase-overproducer Enterobacterales are significantly more resistant to temocillin than ESBL-producing Enterobacterales (37.7% vs 23.5%; P < 0.01);•The rate of temocillin resistance is ...correlated to the number of inactive beta-lactams, ranging from 3.7% to 60.0% in strain susceptible to all beta-lactams and those resistant to 3 beta-lactams;•Among third-generation cephalosporin-resistant Enterobacterales, temocillin was active against 64.9% of the strains nonsusceptible to piperacillin-tazobactam, ofloxacin, and cotrimoxazole.•In ESBL-producing strains, the rate of resistance to temocillin trend to increase from 13.9% in 2014 to 23.9% in 2017 (P < 0.01).
Temocillin is used for several years in some European countries but, only since 2015 in France. We assessed the susceptibility of Enterobacterales strains isolated from blood culture 1 year before (2014) and 2 years after (2017) its use in France. 1,387 strains were included by 17 clinical laboratories located throughout France: 363 in 2014 and 1,024 in 2017. The rate of resistance to temocillin was 4.6% and 26.7% in 3rd generation cephalosporin (3GC) susceptible and resistant strains respectively. Cephalosporinase-overproducer (COPE) strains were significantly more resistant to temocillin (37.7%) than ESBL-producer (ESBL-PE) (23.5%) (P < 0.01). The rate of temocillin resistance was correlated to the number of inactive beta-lactams. The rate of resistance to temocillin trend to increase from 13.9% in 2014 to 23.9% in 2017 (P < 0.01). Temocillin remains highly active against Enterobacterales but the trend in resistance should be assessed over time.
Abstract Background To harmonize with the EUCAST breakpoints, the French Society of Microbiology introduced a change in the inhibition diameter breakpoint (17 mm versus 20 mm previously) of ...temocillin. We assessed the impact of the new breakpoints on categorizing susceptibility of Enterobacterales to temocillin. Methods This was a multicentric retrospective study including all Enterobacterales isolates routinely tested for temocillin susceptibility with the disc diffusion method between 1 January 2016 and 31 July 2022 in four centres. Categorization using the breakpoints of 20 mm (French guidelines CA-SFM/EUCAST 2020 v.1.1) and 17 mm (French guidelines CA-SFM/EUCAST 2021 v1.0 and EUCAST guidelines v11.0) was performed. Results Overall, 36 416 Enterobacterales isolates were included. The overall rate of temocillin resistance decreased from 11.3% to 4.7% (relative difference of 58.5%) when using the 17 mm breakpoint instead of the 20 mm breakpoint, respectively. The relative change ranged from −44.0% in Klebsiella aerogenes to −72.7% in Klebsiella oxytoca. The median inhibition diameter was 23 mm (IQR 21–25). The isolates with a diameter of 20 mm appeared overrepresented, whereas those with a diameter of 18 and 19 mm were underrepresented. We therefore reviewed the diameters between 18 and 21 mm of 273 isolates. Thirty-two (11.7%) of them categorized as susceptible at first measure were controlled resistant at second measure. Conclusions The new breakpoint induced a decrease in the rate of isolates categorized as resistant to temocillin, increasing therapeutic choice including for Extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE). We suggest the bias in measuring the inhibition diameter is probably related to the fact that temocillin is considered remarkably stable against broad-spectrum β-lactamases.
Regular surveys of pneumococcal nasopharyngeal carriage have been conducted among children attending daycare centers in Southeastern France from 1999 to 2012. We compared carriage rate, ...susceptibility patterns and serotype distribution in 2012, following implementation of the 13-valent pneumococcal conjugate vaccine, with findings from 5 previous surveys. Carriage rate was stable, antibiotic susceptibility improved and only serotype 19A persisted among vaccine-types.
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