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PubMed2005

Outer membrane protein profiles of clonally related Klebsiella pneumoniae isolates that differ in cefoxitin resistance.

Eleven genotypically related Klebsiella pneumoniae isolates were obtained from 11 patients. All isolates were resistant to third-generation cephalosporins due to the production of SHV-2a extended-spectrum beta-lactamase. Comparison of the outer membrane protein profiles revealed one isolate that lacked porins. This porin-deficient isolate was also resistant to cefoxitin (MIC 128 microg ml(-1)) and moxalactam (MIC 64 microg ml(-1)) and had elevated MIC of meropenem (2 microg ml(-1)) when compared to porin-expressing isolates (2-8, 4 and <0.06-0.125 microg ml(-1), respectively). Higher MICs, associated with loss of porins in outer membrane, were also observed for cefotaxime (4-8-fold), cefepime (>2-16-fold), ciprofloxacin (4-16-fold), imipenem and aztreonam (2-16-fold), but there was no significant difference among MICs of ceftazidime. The porin-deficient mutant was probably selected in vivo during ofloxacin therapy.

Aged↗

PubMed2026

Insights into the fate and dynamics of antibiotic resistance in multidrug-resistant Bacillus cereus during in vitro simulated gastrointestinal digestion.

Bacillus cereus, an important pathogen responsible for causing foodborne diseases worldwide, releases pore-forming enterotoxins, which target host epithelial cells, leading to osmotic lysis and ultimately manifesting as diarrheal syndrome. Moreover, some B. cereus strains carry antimicrobial resistance genes that confer multidrug resistance against a spectrum of antibiotics. Characterizing the survival traits of multidrug-resistant (MDR) B. cereus strains in the intestinal microenvironment is essential for developing targeted strategies to effectively manage diarrheal foodborne diseases caused by this pathogen. This study used whole-genome sequencing (WGS) to evaluate the pre- and post-digestion toxigenic potential, antimicrobial resistance profiles, and genetic diversity of MDR B. cereus strains isolated from food samples in Guangdong Province, China. The four B. cereus isolates investigated in this study exhibited a genetic diversity, as determined by multilocus sequence typing analysis of WGS data. All four isolates produced the diarrheal toxins Hbl, Nhe, and CytK to varying levels, indicative of their potential to cause outbreaks of foodborne diseases. Each of the four isolates exhibited resistance to more than three classes of antibiotics, fulfilling the criterion for multidrug resistance. At an initial concentration of 9 log colony-forming units (CFU)/mL, the intestinal concentration of these four isolates crossed the threshold required to induce widespread diarrhea in the general population. Under rice slurry protection, all tested isolates maintained intestinal concentration beyond the threshold when the initial concentration was increased to ≥8 log CFU/mL. Moreover, the upregulations of genes associated with acid tolerance, bile tolerance and stress response were observed in the surviving MDR B. cereus isolates. Digestion markedly altered the antibiotic resistance profiles of the MDR B. cereus isolates. In the absence of a food matrix, the MDR isolates lost their resistance to imipenem, meropenem, amoxicillin-clavulanic acid, and trimethoprim-sulfamethoxazole post-digestion and was influenced by the initial concentration of the strains. In the presence of food matrix rice slurry, the effects of digestion on the antibiotic resistance of MDR B. cereus isolates can be mitigated, enabling them to maintain their antibiotic resistance to the greatest extent. Most remarkably, after digestion, the isolates Bce055 and Bce166 exhibited newly emergent resistance to cefotetan and trimethoprim-sulfamethoxazole, respectively. Our findings clarify the fate of MDR B. cereus isolates in the gastrointestinal tract and inform the development of prevention and control strategies for foodborne diseases caused by this pathogen.

Drug Resistance, Multiple, Bacterial↗

PubMed2004

Frequency of Gram-negative bacterial pathogens in bloodstream infections and their resistance to antibiotics in the Czech Republic.

A study performed at 12 hospitals in the Czech Republic in 2001 evaluated the Gram-negative bacterial pathogens most frequently associated with bloodstream infections and their susceptibility to a selection of antimicrobial agents. Of 831 Gram-negative strains, the most frequently isolated organisms were Escherichia coli (32%), Klebsiella pneumoniae (24%) and Pseudomonas aeruginosa (10%). E. coli isolates were relatively susceptible to the antibiotics tested, whereas K. pneumoniae were relatively resistant to all agents except meropenem, and P. aeruginosa to all agents except gentamicin and amikacin. Other agents showed variable rates of resistance to penicillins, third-generation cephalosporins, aminoglycosides and ciprofloxacin.

Anti-Bacterial Agents↗

PubMed2004

Modulation of beta-lactam resistance in Staphylococcus aureus by catechins and gallates.

Aqueous extracts of Japanese green tea (Camellia sinensis) are able to reverse beta-lactam resistance in methicillin-resistant Staphylococcus aureus (MRSA). We have attributed the capacity to reverse oxacillin resistance in the homogeneous PBP2a producer BB568 and in EMRSA-16 to (-)-epicatechin gallate (ECG) and (-)-catechin gallate (CG). Minimum inhibitory concentration (MIC) values for oxacillin were reduced from 256 and 512 to 1-4 mg/l, respectively, in the presence of these polyphenols. In addition, (-)-epigallocatechin gallate (EGCG) had a moderate capacity to modulate oxacillin activity against S. aureus BB568, but none against EMRSA-16. ECG, CG and EGCG increased the sensitivity of EMRSA-15 to oxacillin. The gallate moiety was essential for the oxacillin-modulating activity of ECG, as both (-)-epicatechin and (-)-epicatechin-3-cyclohexylcarboxylate were unable to reverse resistance to oxacillin. Gallic acid and three alkyl gallates (methyl gallate, propyl gallate, and octyl gallate) did not modulate beta-lactam resistance in MRSA. Octyl gallate exhibited direct antibacterial activity against S. aureus BB568 (16 mg/l). Modulation of beta-lactam resistance by ECG significantly enhanced the activities of flucloxacillin and the carbapenem antibiotics imipenem and meropenem against 40 MRSA isolates, with MIC(90) values for the antibiotics reduced to the susceptibility breakpoint or below. Consequently, EGCG, CG and, particularly, ECG warrant further investigation as agents to combat beta-lactam resistance in S. aureus.

Anti-Bacterial Agents↗

PubMed2004

Newer carbapenems for urinary tract infections.

Four carbapenems have been available clinically in Japan. These are imipenem/cilastatin (IMIP/CS) and panipenem/ betamipron (PANI/BP) of the older compounds and newer carbapenems such as biapem (BIAP) and meropenem (MERO). The latter compounds are relatively stable to dehydropeptidase-1 (DHP-1) and have been reported to have higher antimicrobial activities compared to the earlier carbapenems. The antimicrobial activity of these four carbapenems against fresh urinary isolates showed high activities against Enterobacteriacae such as Serratia marcescens, Enterobacter cloacae, Citrobacter freundii and Escherichia coli containing the class C-beta-lactamase- and extended spectrum beta-lactamase (ESBL)-producing strains compared to piperacillin (PIPC) and ceftazidime (CTAZ). Against Pseudomonas aeruginosa, the carbapenems, with the exception of panipenem showed strong antimicrobial activities compared to PIPC and CTAZ. High activities were also seen against Enterococcus faecalis, Staphylococcus aureus and Staphylococcus epidermidis, but methicillin-resistant strains were not affected. The first generation carbapenems showed better activity against E. faecalis than newer carbapenems. All four carbapenems were similar in clinical effectiveness in double blind trials for complicated urinary tract infections (UTIs). However, PANI/BP is less effective in UTIs caused by P. aeruginosa than IMIP/CS. MERO showed better eradication rate of P. aeruginosa than IMIP/CS. Retrospective analysis of treated cases using carbapenems showed a rapid defervescence in the treatment of febrile complicated UTIs, which were mainly caused by mixed infection of Gram-negative and Gram-positive bacteria, especially those involving P. aeruginosa and E. faecalis.

Anti-Bacterial Agents↗

PubMed2005

Dissemination and diversity of metallo-beta-lactamases in Latin America: report from the SENTRY Antimicrobial Surveillance Program.

Carbapenem resistance among Pseudomonas aeruginosa and Acinetobacter spp. is becoming a critical therapeutic problem worldwide. The SENTRY Antimicrobial Surveillance Program monitors pathogen frequency and antimicrobial resistance patterns of nosocomial and community-acquired infections through sentinel hospitals on five continents. Pseudomonas spp. and Acinetobacter spp. strains resistant to imipenem (MIC, >/=16 mg/l), meropenem (MIC, >/=16 mg/l), and ceftazidime (MIC, >/=32 mg/l) collected from January 2001 to December 2003 were routinely screened for antimicrobial resistance genes. Resistant isolates were initially tested for metallo-beta-lactamase (MbetaL) production by phenotypic tests (disk approximation or MbetaL Etest strip) and then characterization of the MbetaL (hydrolysis assays, PCR for bla(IMP), bla(VIM), bla(SPM), gene sequencing). Eighty-nine isolates (33 Acinetobacter spp., 54 Pseudomonas aeruginosa, and 2 P. fluorescens) had positive phenotypic screening tests. Among those, 34 isolates producing MbetaL were identified, including 7 Acinetobacter spp., 25 P. aeruginosa and 2 P. fluorescens. The MbetaLs identified were IMP-1, VIM-2 and two newly described enzymes: SPM-1 and IMP-16. The greatest concentration of MbetaL strains was in Brazil, where imipenem-resistant P. aeruginosa increased significantly in the time period evaluated by the SENTRY Program. MbetaL-producing P. aeruginosa was detected in São Paulo (SPM-1) and Brasilia (SPM-1 and IMP-16), Brazil and Caracas, Venezuela (VIM-2); while MbetaL-producing Acinetobacter spp. isolates were detected in São Paulo, Brazil (IMP-1). P. fluorescens isolates producing IMP-1 and VIM-2 were detected in São Paulo, Brazil and Santiago, Chile, respectively. The emergence and dissemination of mobile MbetaL-producing isolates represent an alarming factor for increasing resistance to carbapenems in several medical centres evaluated by the SENTRY Program in Latin America.

Acinetobacter↗

PubMed2005

Antimicrobial use and Pseudomonas aeruginosa susceptibility profile in a cystic fibrosis centre.

The susceptibility patterns of 1315 mucoid and non-mucoid Pseudomonas aeruginosa strains from 224 patients were determined along with antibiotic utilisation in a Cystic Fibrosis Centre from 1993 to 1997. Ceftazidime was the most active agent (86.0% sensitive isolates), followed by piperacillin-tazobactam (81.7%), aztreonam (80.3%), imipenem (80%), piperacillin (76.8%), tobramycin (76.5%), ciprofloxacin (73.7%), ticarcillin (72.4%), ticarcillin-clavulanic acid (70.2%), amikacin (69.5%), netilmicin (56.5%), meropenem (79%) and imipenem (75.5%). The most frequently used compounds were nebulized colistin (mean+/-S.D., 109+/-45 defined daily doses per 1000 patients per day), followed by ciprofloxacin (98+/-8), tobramycin (55+/-9), ceftazidime (31+/-8) and amikacin (55+/-9). The mean antibiotic consumption by our CF patients was 413+/-47 defined daily doses per 1000 patients per day. Trend testing showed a significant decline of susceptibility to aminoglycosides, imipenem and ciprofloxacin, while the susceptibility of P. aeruginosa to piperacillin and ceftazidime was stable.

Adolescent↗

PubMed2006

In vivo selection of Enterobacter aerogenes with reduced susceptibility to cefepime and carbapenems associated with decreased expression of a 40 kDa outer membrane protein and hyperproduction of AmpC beta-lactamase.

The mechanism(s) of resistance or decreased susceptibility to cefepime (FEP) and/or imipenem (IMP) in three consecutive isolates of Enterobacter aerogenes (Ea1, Ea2 and Ea3) cultured from bronchial aspirates of the same patient after treatment with ceftriaxone and FEP were studied. Identification was performed with the VITEK 2 system. All three isolates showed identical pulsed-field gel electrophoresis patterns and were resistant (minimum inhibitory concentrations (MICs)) to cefoxitin (MIC, >1024 mg/L), cefotaxime (CTX; MIC, 32-128 mg/L) and ceftazidime (CAZ; MIC, 32-128 mg/L) but susceptible to meropenem (MIC, Glu. Three outer membrane proteins (OMPs) of 51 kDa, 40 kDa and 38 kDa were observed in the three isolates by sodium dodecylsulphate-polyacrylamide gel electrophoresis (SDS-PAGE) (10% polyacrylamide gels with 4 M urea), although expression of the 40 kDa OMP was reduced in Ea2. In conclusion, decreased susceptibility to FEP and IMP in Ea2 is related to reduced expression of a 40 kDa OMP and hyperproduction of AmpC, whereas resistance to FEP in Ea3 is associated with hyperproduction of an altered AmpC.

Anti-Bacterial Agents↗

PubMed2006

Prevalence of extended-spectrum beta-lactamase-positive Klebsiella pneumoniae isolates in the Czech Republic.

This study focused on the prevalence and molecular biology of extended-spectrum beta-lactamase (ESBL)-positive Klebsiella pneumoniae isolates collected in the Czech Republic. Clinical material from patients hospitalised in 16 Czech hospitals in September 2004 was used to isolate K. pneumoniae strains. Strains were identified by standard identification procedures. Susceptibility of the strains to antibiotics was tested using a microdilution method. The double-disk synergy test and combination disk method were used to determine ESBL production. Molecular biology characteristics of ESBL-positive isolates were determined using genomic DNA isolation, XbaI restriction digestion and pulsed-field gel electrophoresis differentiation. The acquired restriction maps of individual isolates were compared using GelCompar II software and their relationships were determined. During the 3-week period, 483 K. pneumoniae strains causing clinically detectable diseases were isolated. Of these, 117 (24.2%) were determined to be ESBL-positive. The prevalence of ESBL-positive isolates was 38.9% in Intensive Care Units (ICUs) and 13.1% in standard wards. More than 50% of ESBL-positive isolates were treated effectively only with meropenem (98%), cefoperazone/sulbactam (61%) and amikacin (54%). Conversely, ESBL-negative isolates showed high susceptibility to all tested antibiotics (76-99%). Molecular biology analysis identified 18 clonal types containing two to six identical isolates. Seventeen clones usually contained isolates from only one hospital; isolates from two hospitals were identified only in one clone. Based on the abovementioned results, the prevalence of ESBL-positive K. pneumoniae isolates in the Czech Republic can be perceived as relatively high, especially in ICUs. Extensive spread of 'epidemic clones' within Czech hospitals and, to a limited extent, between them can be demonstrated.

Czech Republic↗

PubMed2006

CTX-M-37 in Salmonella enterica serotype Isangi from Durban, South Africa.

Beta-lactamase-mediated resistance was investigated in 59 putative extended-spectrum beta-lactamase (ESBL)-positive Salmonella spp. from the paediatric ward of a tertiary hospital in Durban, South Africa. Three Salmonella enterica serotype Isangi cultured from stool samples were multidrug resistant, with susceptibility only to meropenem, piperacillin/tazobactam and cefoxitin. Isoelectric focusing revealed beta-lactamases with isoelectric points of pI 5.8, 6.8 and 7.2. Sequencing identified beta-lactamases CTX-M-37 and TEM-1. To our knowledge, this is the first report of CTX-M-37 from S. enterica serotype Isangi in South Africa.

Anti-Bacterial Agents↗

PubMed2006

Increase of imipenem resistance among Pseudomonas aeruginosa isolates from a Polish paediatric hospital (1993-2002).

Analysis of the in vitro activity of imipenem and 13 other antibiotics against 2485 Pseudomonas aeruginosa isolates obtained from clinical specimens from children hospitalized during 1993-2002 was performed. In 2002, the percentage of P. aeruginosa isolates susceptible to all tested antibiotics, with the exception of imipenem, increased or remained on nearly the same level as in 1993. An increase of resistance to imipenem from 4.3% to 18.3% was observed. The MIC(90) value of imipenem increased from 2mg/L to 16 mg/L. Simultaneously, a four-fold increase of the usage of carbapenems imipenem and meropenem in the hospital was noted. In 2000-2001, a high incidence of imipenem-resistant strains was observed. The imipenem-resistant P. aeruginosa strains of serotype O6 from the general surgery ward and serotype O11 from the intensive care unit were shown to be clonally related by the pulsed-field gel electrophoresis method.

Anti-Bacterial Agents↗

PubMed2007

Biochemical characterisation of the CTX-M-14 beta-lactamase.

Cefotaxime-resistant Escherichia coli TUM1121 was isolated from an abscess of an 83-year-old patient. The CTX-M-14 gene was located on a 70 kb plasmid. The enzyme was purified and its activity was analysed. CTX-M-14 was poorly active against ceftazidime and aztreonam. Aztreonam behaved as a competitive inhibitor. Among the tested suicide substrates for class A beta-lactamases, sulbactam was a rather good substrate. Tazobactam and clavulanic acid behaved as inactivators. The interactions between clavulanic acid and CTX-M-14 were characterised by progressive inactivation of the beta-lactamase. Carbapenems such as imipenem, meropenem or doripenem did not behave as inactivators of CTX-M-14, however very small k(cat) values were observed. This result shows that CTX-M-14 is able to hydrolyse carbapenems.

Cloning, Molecular↗

PubMed2007

Reduced imipenem susceptibility in Klebsiella pneumoniae clinical isolates with plasmid-mediated CMY-2 and DHA-1 beta-lactamases co-mediated by porin loss.

We investigated the resistance mechanisms and clonality among 42 imipenem-non-susceptible Klebsiella pneumoniae isolated at a tertiary care hospital in Korea. Two isolates had bla(VIM-2) alleles, whereas bla(CMY-2)- and bla(DHA-1)-like alleles were detected in 24 and 16 isolates, respectively, with these enzymes confirmed by sequencing for representative isolates. Transfer of bla(CMY-2) and bla(DHA-1) was achieved by conjugation. Addition of 300 mg/L 3-aminophenylboronic acid (APB) reduced the minimum inhibitory concentration for 90% of the organisms (MIC(90)) of imipenem and meropenem eight- and four-fold, respectively, for the bla(CMY-2)- and bla(DHA-1)-positive isolates, confirming the role of these enzymes in resistance. SDS-PAGE of outer membrane proteins for representative isolates showed lack or greatly diminished expression of OmpK35 and OmpK36 porins. Pulsed-field gel electrophoresis of XbaI-restricted genomic DNA revealed two closely related clusters among 23 bla(CMY-2)-positive isolates, whereas those with bla(DHA-1) were more heterogeneous. In conclusion, reduced imipenem susceptibility among K. pneumoniae at this Korean hospital was largely co-mediated by production of plasmid-mediated AmpC beta-lactamases along with lack or greatly diminished expression of OmpK35 and OmpK36 porins.

Anti-Bacterial Agents↗

PubMedDate not supplied

Bacteriological study of diabetic foot infections.

AIMS: The polymicrobial nature of diabetic foot infection has been well documented in the literature. Patients with diabetic foot infection not exposed to antibiotics are not well studied before. The relative frequency of bacterial isolates cultured from community-acquired foot infections that are not exposed to antimicrobial agents for 30 days is studied. In addition, the bacterial comparative in vitro susceptibility to the commonly used antibacterial agents is assessed. METHODS: This is a prospective study in which the infected wounds of 86 consecutive diabetic patients seen in the diabetic foot clinic in Adan Teaching Hospital were cultured when visiting the clinic. The patients did not receive antimicrobial therapy 30 days prior to taking the cultures. The specimen was cultured using aerobic and anaerobic microbiological techniques. Isolates were tested for susceptibility to commonly used antimicrobial therapy. RESULT: Staphylococcus aureus was the most common isolate, being recovered from 38.4% of cases. Other organisms were Pseudomonas aeruginosa (17.5%) and Proteus mirabilis (18%), anaerobic gram-negative organisms (10.5%), mainly Bacteroides fragilis. Imipenem, meropenem, and cefepime were the most effective agents against gram-negative organisms. Vancomycin was the most effective against gram-positive organisms. CONCLUSION: S. aureus and P. aeruginosa were the most common causes of diabetic foot infections. Anaerobic organisms are still a common cause for infection, although the prevalence is less. These wounds may require use of combined antimicrobial therapy for initial management.

Adult↗

PubMed2004

Clinical surveillance of surgical imipenem-resistant Pseudomonas aeruginosa infection in a Japanese hospital.

In order to elucidate any changes in imipenem-resistant Pseudomonas aeruginosa (IRPA) infections in Japan, we examined 511 P. aeruginosa stains isolated from our surgical ward between 1987 and 2001. These isolates were subjected to susceptibility testing against various antipseudomonal agents including imipenem, meropenem, ceftazidime, gentamicin and ciprofloxacin. They were serotyped with the slide agglutination test and genotyped using pulsed-field gel electrophoresis (PFGE). The annual incidences of IRPA infections were particularly high in the early 1990s. Epidemiological investigations revealed that these outbreaks were due to dissemination of hospital-acquired IRPA isolates. Intensive use of imipenem promoted the selection of highly resistant strains. Further study of resistance mechanisms revealed that none of the 110 IRPA strains were metallo-beta-lactamase (MBL) producers. Polymerase chain reaction (PCR) analysis using bla(IMP) specific primers confirmed that no IMP-1 type MBL gene-positive strains were detected from our ward. Susceptibilities of those IRPA strains against other antipseudomonal agents showed relatively low levels, suggesting that imipenem resistance was mainly due to impermeability of the OprD porin. In conclusion, hospital-acquired outbreaks of IRPA were recently reduced by guidelines for, and surveillance of, appropriate use of antimicrobial agents. When the rate of IRPA isolation increases, serotyping should be performed initially and PFGE is required to confirm outbreaks. A computer-assisted genotyping technique is available to perform epidemiological studies of IRPA isolates.

Anti-Bacterial Agents↗

PubMed2026

Genome-sequencing-based benchmarking of antimicrobial resistance, treatment outcomes and healthcare transmission events for Clostridioides difficile infection in Australian hospitals.

BACKGROUND: Clostridioides difficile infection (CDI) remains a priority for infection prevention and control in health care, particularly with the emergence of hypervirulent strains and antimicrobial resistance (AMR). AIM: To characterize the genomic epidemiology and AMR profiles of culture-confirmed CDI cases within tertiary hospitals in Australia. METHODS: A total of 155 C. difficile isolates from 142 patients with CDI diagnosed in four hospitals between 2023 and 2025 were studied. Data collected included patient demographics, severity of infection, antibiotic treatment and clinical outcomes at 8 weeks. Phenotypic susceptibility to vancomycin, fidaxomicin, metronidazole, moxifloxacin, meropenem, tetracycline and rifaximin were determined by agar dilution. Isolates underwent whole-genome sequencing (WGS) for genotyping and resistome assessment. FINDINGS: WGS differentiated 39 distinct sequence types among CDI isolates across different healthcare services. In total, 100 isolates were singletons and 55 (35% clustering rate) isolates were considered to be genomically related (difference of two or fewer single-nucleotide polymorphisms). Of these, 12 patients (8.5%) with close hospital contact formed six epidemiologically linked clusters. Phenotypic susceptibility results were obtained for 134 (86.4%) CDI isolates. There was no phenotypic resistance to vancomycin [minimum inhibitory concentration required to inhibit the growth of 90% of isolates (MIC90) 1 mg/L], metronidazole (MIC90 0.5 mg/L) or fidaxomicin (MIC90 0.5 mg/L). There was no association in the study cohort between the presence of resistance genes or reduced phenotypic susceptibility and CDI recurrence. CONCLUSION: Genomic analysis of C. difficile isolates did not identify any outbreaks or an association between the sequence type or presence of a resistance gene and clinical outcomes. High-resolution characterization and identification of antibiotic resistance, CDI clinical relapse and recent transmission offered by genome sequencing can provide important benchmarks for hospital infection control.

Antibiotic resistance↗

PubMed2026

Treatment strategies for imipenemase-producing Gram-negative infections: lessons from Japan.

Carbapenems remain essential for treating serious infections caused by drug-resistant Gram-negative bacteria because of their broad-spectrum activities and favourable safety profiles. However, the emergence of carbapenemase-producing Enterobacterales, which produce enzymes that efficiently hydrolyse β-lactams including carbapenems, continues to undermine their clinical utility. Although new antibiotics such as ceftazidime-avibactam, imipenem-relebactam, meropenem-vaborbactam, aztreonam-avibactam, and cefiderocol have expanded therapeutic options, their effectiveness varies substantially across different carbapenemase families. Carbapenemases produced by Enterobacterales include serine β-lactamases (Ambler classes A and D) and metallo-β-lactamases (MBLs; Ambler class B), each with distinct substrate and inhibitor profiles. Clinically relevant MBLs-including imipenemase (IMP), New Delhi MBL (NDM), and Verona integron-encoded MBL (VIM) variants-show markedly different biochemical properties and inhibitor susceptibilities. Despite their clinical relevance, optimal treatment strategies for infections caused by IMP-producing Enterobacterales remain poorly defined. The unique reactivity of IMP-type MBLs to inhibitors differs from that of other MBLs such as NDMs or VIMs, underscoring the need for tailored therapeutic approaches. In this Personal View, we summarise current evidence and, drawing on Japan's experience as an endemic setting for IMP producers, outline key scientific, clinical, and public health challenges that should be addressed globally to develop effective, evidence-based treatment strategies for IMP-producing Enterobacterales infections.

Humans↗

PubMed2004

Pleiotropic effect of sodium arsenite on Escherichia coli.

The effects of sodium arsenite at a sub-MIC concentration (25 mg/l) upon different bacterial functions were studied. This compound reduced the killing activity of nalidixic acid, amikacin, and meropenem. It also promoted the loss of F'lac from bacterial hosts and increased the number of recombinants in conjugation and transduction experiments. Transposition of Tn9 was also enhanced by the salt. In addition, sodium arsenite abolished the lethal effect of temperature on thermosusceptible DNA synthesis mutants in a similar manner to that seen in an anaerobic environment. Finally at a low dose, it induced the SOS response, and the related production of recA-dependent enzymes was reduced as the sodium arsenite concentration increased. It has been suggested that arsenite primarily affects the uvrA gene product, influencing the other bacterial functions studied. The energetic depletion caused by this compound appears to play a role in the activity of autolytic enzymes.

Arsenites↗