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Antibiotics are one of the greatest advances in modern medicine. Antibiotic resistance is one of the most serious threats to global health, aggravating the prognosis of immunocompromised patients, especially burn patients. Our objective was to study the consumption of antibiotics of critical importance according to the WHO and the correlation between antibiotic resistance in Pseudomonas æruginosa and the consumption of these antibiotics. Our study took place in the Medical Laboratory in collaboration with the Trauma and Burn Center's Burn Unit in Tunisia. In our retrospective study, 1384 non-repetitive strains of Pseudomonas æruginosa responsible for colonization or infection were included, between January 2012 and December 2019. Pseudomonas æruginosa was the most isolated bacterial strain in the service, with an average rate of 15.9% of the service's bacterial ecology. The antibiotic resistance rates tested were high: 77.1% to piperacillin-tazobactam, 56% to ceftazidime, 74.9% to imipenem, 78.8% to amikacin, 54.7% to ciprofloxacin and 32.8% to fosfomycin. Among our strains, 81.8% were multi drug-resistant strains. The analysis of the correlation between the level of consumption of antibiotics and the antibiotic resistance levels in Pseudomonas æruginosa showed that the increased consumption of piperacillin-tazobactam increased resistance not only to piperacillin-tazobactam but also to imipenem and amikacin as well as multi drug resistance. Similarly, the increase in the consumption of fosfomycin correlates with resistance to piperacillin-tazobactam and imipenem. [ABSTRACT FROM AUTHOR]

Nosocomial bacteremia (NB) is one of the most severe infections in burns in intensive care units. Their prognosis is worsened with the emergence and spread of multidrug resistant bacteria (MDR). Our retrospective study aimed to investigate clinical and bacteriological characteristics of NB occurring in patients hospitalized in the Trauma and Burn Center's Burn Unit (TBC-BU) in Tunisia, during a 3-year period (2016-2018). We found 261 NB in 216 patients, for a prevalence of 25.7% and an incidence density of 13.4‰ days of in-patient stay. The vast majority (88.9%) of NB occurred during the first 2 weeks of hospitalization. The catheterrelated bacteremia rate was 11.1%. P. æruginosa (20.2%) and A. baumannii (16.8%) were the 2 species most frequently isolated when S. aureus represented only 7.5% of isolates. Resistance rates were high, with 71% of P. æruginosa resistant to ceftazidime, 64% of S. aureus being MRSA, 69,5% of resistance to 3rd generation cephalosporins among Enterobacteriaceae, and colimycin remaining the only regularly active antibiotic (98%) on A. baumannii. The MDR rate was 44%, represented mainly by A. baumannii, ESBL-E and P. æruginosa. The mortality rate due to NB was 25%, with a significantly higher rate of MDR in fatal NB compared to that in NB with favorable outcome (p = 0,000019). [ABSTRACT FROM AUTHOR]

Pseudomonas æruginosa (PA) is among the major agents of infection in burns. Multidrug-resistant strains are commonly isolated, which hampers the management of these patients. Our purpose was to study the incidence density of PA colonization and PA infection and to investigate the antibiotic susceptibility of strains isolated in patients hospitalized in the Trauma and Burn Center's Burn Unit (TBC-BU) in Tunisia. It is a retrospective study including 1649 non-repetitive strains of PA during an 8-year period (2012- 2019). PA was the most common organism in TBC-BU bacterial ecology (15%). The incidence density of PA colonization and PA infection was 16.1‰ days of in-patient stay (DH) and 16.5‰ DH, respectively. A positive and statistically significant correlation was found between PA colonization and PA infection (rs=1; p=0,004). The colonization strains were mainly isolated from skin (25.1%) and central catheters (22.3%). Bacteremia was the most common infection (19.5%). The skin was the most common source of bacteremia (22.1%) followed by central catheters (18.3%). The highest rates of antibiotic resistance were found with piperacillin-tazobactam (72.4%), ceftazidime (49.4%), meropenem (74%), imipenem (70.5%), amikacin (74.6%), ciprofloxacin (56.5%) and fosfomycin (35.3%). We did not identify any colistin-resistant strain. The multidrug resistance rate was 78%. The metallo-carbapenemase-producing strains rate was 14.4%. [ABSTRACT FROM AUTHOR]

Aims: Carbapenem-resistant Acinetobacter baumannii (CR-Ab) is an important cause of infections in burn patients. This study aimed to characterize the antimicrobial susceptibility pattern of CR-Ab isolated from burns in Burn Intensive Care Unit (BICU) of the Trauma and Burn Centre of Ben Arous, to determine the prevalence of β-lactamase-encoding genes and to search eventual genetic relatedness of CR-Ab strains., Methods and Results: From 15 December 2016 to 2 April 2017, all nonduplicated CR-Ab isolated in burn patients in the BICU were screened by simplex Polymerase Chain Reaction (PCR) for the class A, B, C, and D β-lactamase genes. Sequencing was performed for NDM gene only. Genetic relatedness was determined by using pulsed field gel electrophoresis (PFGE) and by multilocus sequence typing. During the study period, 34 strains of CR-Ab were isolated in burns, mainly in blood culture (n = 14) and central vascular catheter (n = 10). CR-Ab strains were susceptible to colistin but resistant to amikacin (91%), ciprofloxacin (100%), rifampicin (97%), and trimethoprim-sulfamethoxazole (100%). All strains harbored blaOXA-51-like and blaOXA-23 genes, only or associated to blaGES (n = 26; 76%), blaADC (n = 20; 59%), blaPER-1 (n = 6; 18%) or/and blaNDM-1 (n = 3; 9%). PFGE identified 16 different clusters and revealed that most strains belonged to one major cluster A (n = 15; 44.1%). Among NDM-1 isolates, two were clonally related in PFGE and belonged to two single locus variant sequence type ST-6 and ST-85., Conclusions: This is the first description of clonally related NDM-1 and OXA-23-producing A. baumannii strains in the largest Tunisian BICU associated with two single locus variant sequence types ST6 and ST85., (© The Author(s) 2024. Published by Oxford University Press on behalf of Applied Microbiology International.)

Carbapenem resistant Enterobacteriaceae (CRE) are major human pathogens because, these cause high number of difficult-to-treat infections. Allogeneic hematopoietic stem cell transplant (AHSCT) recipients are highly exposed to these type of bacteria. The aim of our study was to investigate prevalence of CRE colonization in AHSCT patients and to determine genes encoding carbapenem resistance. A retrospective study conducted between January 2015 and December 2019, involved 55 patients colonized with CRE strains. We determined the rate of antibiotic resistance according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the carbapenem resistance genes by PCR assays for genes encoding most frequent β-lactamases namely, blaGES, blaKPC, blaIMI, blaNDM, blaVIM, blaIMP and blaOXA-48. Eighty-one episodes of CRE colonization were recorded in 55 patients, mainly suffering from acute leukaemia (30%) and aplastic anemia (26%). History of hospitalization was noted in 80 episodes. Prior antibiotic treatment, severe neutropenia and corticosteroid therapy were respectively found in 94%, 76% and 58% of cases. Among the 55 patients, six patients (11%) developed a CRE infection. The CRE responsible for colonization were carbapenemase producers in 90% of cases. They belonged mostly to Klebsiella pneumoniae (61/81) and Escherichia coli species (10/81). Antibiotic resistance rates were 100% for ertapenem, 53% for imipenem, 42% for amikacin, 88% for ciprofloxacin and 27% for fosfomycin. Molecular study showed that blaOXA-48 gene was the most frequent (60.5%), followed by blaNDM (58%). Thirty-five (43%) strains were co-producers of carbapenemases. In our study, we report a high rate of CRE intestinal colonization in AHSCT recipients of our center.

Introduction: Considering the growing global need and the complexity of health conditions, an intensive rehabilitation in inpatient departments is fundamental. Yet, in Tunisia, the distribution of Inpatient Rehabilitation Facilities is not illustrated., Aim: To perform an update concerning the rehabilitation's beds-ratio /1000 Tunisian-inhabitants in 2023., Methods: Data were collected from the Tunisian Ministry of Health, the Eastern Mediterranean Regional Office, and the National Institute of Statistics websites., Results: The findings revealed a total number of rehabilitations' beds 132 among a total of 20000 hospital beds with a rehabilitations' beds-ratio equal to 0.01/1000 inhabitants. Only three Inpatient Rehabilitation Facilities were identified in Tunisia covering the Greater Tunis, North East, and Center east districts. There was inequity of distribution since the beds ratio is 1.07/1000 in the North east, 0.02/1000 in the Greater Tunis and 0 in the North West and the South of Tunisia., Conclusion: This update highlighted the alarmingly low rehabilitation's beds-ratio in Tunisia, coupled to a significant regional disparity. Increasing beds in the existing Inpatient Rehabilitation Facilities and extending outpatient rehabilitation departments with inpatient units might be considered urgent solutions.

Acinetobacter baumannii has emerged as a main nosocomial pathogen exhibiting high rates of resistance to clinically relevant antibiotics. Six pandrug-resistant A. baumannii (PDR-A. baumannii) were recovered from three patients in a Tunisian Intensive Care Unit (ICU) between 10th and 16th of May 2018 resulting in one fatal case and raising the possibility of an outbreak. On 18th of May environmental screening of ICU surfaces was carried out. On 22nd of May a fourth patient was infected with PDR-A. baumannii and died. A second investigation was carried out for environmental screening and PDR-A. baumannii was isolated from the respirator. Antimicrobial susceptibility testing was performed according to EUCAST (2019) guidelines. MIC of colistin was determined by broth microdilution method. PCR was used to detect 14 beta-lactamases/carbapenemases and mcr (mcr-1 to mcr-5) genes. The genetic relatedness of PDR-A. baumannii isolates was determined by PFGE and MLST. Seven PDR-A. baumannii isolates were recovered from four patients, one MDR strain from wash basin, a PDR strain from hand sanitizer bottle and another PDR strain from respirator. All PDR-A. baumannii (n = 9) harbored blaOXA-69 gene and none carried mcr. Moreover, seven carried blaGES and blaOXA-23 genes. PFGE identified four pulsotypes (A, B, C, and D) with the pulsotype A gathering seven PDR-A. baumannii isolates: six from three patients and one from hygiene sample. MLST revealed that all PDR-A. baumannii isolates of pulsotype A belonged to the pandemic clone ST2. Systematic screening of MDR and PDR-A. baumannii is highly recommended to limit dissemination of such strains in ICUs.

Pseudomonas aeruginosa is one of the major infectious agents in burn patients. Globally, high rates of antimicrobial resistance in P. aeruginosa have been reported, which is a cause of concern. The objective of this study was to determine the rate of resistance to carbapenems in P. aeruginosa isolates recovered from burn patients in Tunisia, to search genes encoding for carbapenemases and to determine their epidemiological markers (serotypes). A retrospective study was conducted in the Burn Intensive Care Unit (BICU) of the Trauma and Burn Centre of Ben Arous, Tunisia, and P. aeruginosa isolates collected from burn patients, from January to December 2018 were investigated. Carbapenemase screening was performed by Carbapenem Inactivation Method (CIM) and by EDTA-disk test for all carbapenem resistant isolates. Genes encoding carbapenemases (blaVIM, blaIMP, blaGES, blaNDM, and blaKPC) were investigated by PCR and selected carbapenemase genes were sequenced. During the study period, 104 non duplicated P. aeruginosa isolates were recovered. Most of them were isolated from skin samples (45.1%) and blood culture (22.1%) and belonged to O:11 (19.2%), O:12, and O:5 (12.5%, each) serotypes. High rates of resistance were observed for carbapenems (64.4%). Among the 67 carbapenem resistant isolates, 58 (86.5%) harbored blaVIM gene and 55 (82%) blaGES gene; in addition, 48 (71.6%) co-harbored blaVIM and blaGES genes. After sequencing, the blaVIM-2 and blaGES-5 gene variants were identified in seven randomly selected isolates. To the best of our knowledge, this is the first description of P. aeruginosa simultaneously harboring blaVIM-2 and blaGES-5 genes.

Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen causing health care-infections in the world, especially in burns. The aim of this study was to assess the extent of dissemination of MRSA isolated from burn patients in Burn Intensive Care Unit in Tunisia and to evaluate the frequency of virulence and antibiotics resistance genes. Among the 72 S. aureus isolates analyzed in the study, 54% were MRSA. The majority of MRSA (94.8%) were multidrug resistant and they had a high resistance rates to kanamycin (94.8%), tobramycin (90%), tetracycline (94.8%) and ciprofloxacin and rifampicin (87%, each). The gene aac(6')-Ie-aph(2″)-Ia conferring resistance to kanamycine and tobtamycin were detected in all isolates and the aph(3')-Ia gene conferring resistance to gentamicin were detected in 2.8% of resistant isolates. Tetracycline resistance genes tet(M), tet(K) and tet(L) were detected in 100%, 10.8% and 2.8% of the isolates, respectively. The SCCmec type III and the agr type I were the most predominant (69.2% and 90%, respectively). The 27 SCCmecIII-agrI isolates were clustered into two PFGE types A and B. The two representative isolates of PFGE clusters A and B belonged to ST239-t037 and ST241-t037 respectively. As conclusion, our results showed a high prevalence of MRSA in trauma burn intensive care unit belonging to two multidrug resistant clones ST239/ST241-agrI-t037-SCCmecIII MRSA. We also demonstrated that MRSA was disseminated between burn patients.

Smoothened (SMO) transduces the Hedgehog (Hh) signal across the plasma membrane in response to accessible cholesterol. Cholesterol binds SMO at two sites: one in the extracellular cysteine-rich domain (CRD) and a second in the transmembrane domain (TMD). How these two sterol-binding sites mediate SMO activation in response to the ligand Sonic Hedgehog (SHH) remains unknown. We find that mutations in the CRD (but not the TMD) reduce the fold increase in SMO activity triggered by SHH. SHH also promotes the photocrosslinking of a sterol analog to the CRD in intact cells. In contrast, sterol binding to the TMD site boosts SMO activity regardless of SHH exposure. Mutational and computational analyses show that these sites are in allosteric communication despite being 45 angstroms apart. Hence, sterols function as both SHH-regulated orthosteric ligands at the CRD and allosteric ligands at the TMD to regulate SMO activity and Hh signaling.

A long-standing mystery in vertebrate Hedgehog signaling is how Patched 1 (PTCH1), the receptor for Hedgehog ligands, inhibits the activity of Smoothened, the protein that transmits the signal across the membrane. We previously proposed (Kinnebrew et al., 2019) that PTCH1 inhibits Smoothened by depleting accessible cholesterol from the ciliary membrane. Using a new imaging-based assay to directly measure the transport activity of PTCH1, we find that PTCH1 depletes accessible cholesterol from the outer leaflet of the plasma membrane. This transport activity is terminated by binding of Hedgehog ligands to PTCH1 or by dissipation of the transmembrane potassium gradient. These results point to the unexpected model that PTCH1 moves cholesterol from the outer to the inner leaflet of the membrane in exchange for potassium ion export in the opposite direction. Our study provides a plausible solution for how PTCH1 inhibits SMO by changing the organization of cholesterol in membranes and establishes a general framework for studying how proteins change cholesterol accessibility to regulate membrane-dependent processes in cells., Competing Interests: MK, GL, RS, SF, LV, TN, FB, YS, CS, RR No competing interests declared, AR is a reviewing editor for eLife, (© 2021, Kinnebrew et al.)

Antibiotics are one of the greatest advances in modern medicine. Antibiotic resistance is one of the most serious threats to global health, aggravating the prognosis of immunocompromised patients, especially burn patients. Our objective was to study the consumption of antibiotics of critical importance according to the WHO and the correlation between antibiotic resistance in Pseudomonas æruginosa and the consumption of these antibiotics. Our study took place in the Medical Laboratory in collaboration with the Trauma and Burn Center's Burn Unit in Tunisia. In our retrospective study, 1384 non-repetitive strains of Pseudomonas æruginosa responsible for colonization or infection were included, between January 2012 and December 2019. Pseudomonas æruginosa was the most isolated bacterial strain in the service, with an average rate of 15.9% of the service's bacterial ecology. The antibiotic resistance rates tested were high: 77.1% to piperacillin-tazobactam, 56% to ceftazidime, 74.9% to imipenem, 78.8% to amikacin, 54.7% to ciprofloxacin and 32.8% to fosfomycin. Among our strains, 81.8% were multi drug-resistant strains. The analysis of the correlation between the level of consumption of antibiotics and the antibiotic resistance levels in Pseudomonas æruginosa showed that the increased consumption of piperacillin-tazobactam increased resistance not only to piperacillin-tazobactam but also to imipenem and amikacin as well as multi drug resistance. Similarly, the increase in the consumption of fosfomycin correlates with resistance to piperacillin-tazobactam and imipenem., (Copyright © 2021 Euro-Mediterranean Council for Burns and Fire Disasters.)

The purpose of our study was to investigate the epidemiology of coagulase negative staphylococci (CoNS) responsible for bacteremia in hematopoietic stem cell transplant (HSCT) recipients and to determine the prevalence and the genetic background of methicillin resistance. The prevalence of CoNS bacteremia was 7.4% (54/728), higher in allograft (10.7%) than in autograft (4.7%) recipients. A sepsis or a septic shock were observed in 9% of cases. No deaths were attributable to CoNS bacteremia. The methicillin resistance rate was 81%. All MR-CoNS, harbored mecA gene and 90% were typeable with SCCmec typing using PCR amplification. The SCCmec type IV was the most frequent (44%). Clonal dissemination of MR- Staphylococcus epidermidis strains was limited. Our study showed a low prevalence and favorable outcome of CoNS bacteremia in HSCT recipients with limited clonal diffusion. However, they were associated with a significant rate of severe infections and a high rate of methicillin resistance, mediated by SCCmec IV element in most cases.

Nosocomial bacteremia (NB) is one of the most severe infections in burns in intensive care units. Their prognosis is worsened with the emergence and spread of multidrug resistant bacteria (MDR). Our retrospective study aimed to investigate clinical and bacteriological characteristics of NB occurring in patients hospitalized in the Trauma and Burn Center's Burn Unit (TBC-BU) in Tunisia, during a 3-year period (2016-2018). We found 261 NB in 216 patients, for a prevalence of 25.7% and an incidence density of 13.4‰ days of in-patient stay. The vast majority (88.9%) of NB occurred during the first 2 weeks of hospitalization. The catheterrelated bacteremia rate was 11.1%. P. æruginosa (20.2%) and A. baumannii (16.8%) were the 2 species most frequently isolated when S. aureus represented only 7.5% of isolates. Resistance rates were high, with 71% of P. æruginosa resistant to ceftazidime, 64% of S. aureus being MRSA, 69,5% of resistance to 3rd generation cephalosporins among Enterobacteriaceae, and colimycin remaining the only regularly active antibiotic (98%) on A. baumannii. The MDR rate was 44%, represented mainly by A. baumannii, ESBL-E and P. æruginosa. The mortality rate due to NB was 25%, with a significantly higher rate of MDR in fatal NB compared to that in NB with favorable outcome (p = 0,000019)., (Copyright © 2021 Euro-Mediterranean Council for Burns and Fire Disasters.)

Pseudomonas æruginosa (PA) is among the major agents of infection in burns. Multidrug-resistant strains are commonly isolated, which hampers the management of these patients. Our purpose was to study the incidence density of PA colonization and PA infection and to investigate the antibiotic susceptibility of strains isolated in patients hospitalized in the Trauma and Burn Center's Burn Unit (TBC-BU) in Tunisia. It is a retrospective study including 1649 non-repetitive strains of PA during an 8-year period (2012- 2019). PA was the most common organism in TBC-BU bacterial ecology (15%). The incidence density of PA colonization and PA infection was 16.1‰ days of in-patient stay (DH) and 16.5‰ DH, respectively. A positive and statistically significant correlation was found between PA colonization and PA infection (rs=1; p=0,004). The colonization strains were mainly isolated from skin (25.1%) and central catheters (22.3%). Bacteremia was the most common infection (19.5%). The skin was the most common source of bacteremia (22.1%) followed by central catheters (18.3%). The highest rates of antibiotic resistance were found with piperacillin-tazobactam (72.4%), ceftazidime (49.4%), meropenem (74%), imipenem (70.5%), amikacin (74.6%), ciprofloxacin (56.5%) and fosfomycin (35.3%). We did not identify any colistin-resistant strain. The multidrug resistance rate was 78%. The metallo-carbapenemase-producing strains rate was 14.4%., (Copyright © 2020 Euro-Mediterranean Council for Burns and Fire Disasters.)