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Antibiotics, Volume 13, Issue 3 (March 2024) – 92 articles

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Partially metabolized antimicrobials from humans, animals, and agricultural practices have been identified as a primary source of environmental contamination. However, limited research has explored the environmental contribution to bacterial antimicrobial resistance (AMR). Bacteria originating from different sources exhibit distinct resistance patterns due to different evolutionary trajectories. The level of AMR in Escherichia coli (E. coli) is commonly used as an indicator in AMR monitoring programs. This study aims to evaluate the landscape of AMR in E. coli isolated from diverse environmental samples in Central Virginia. The findings will pave the way for the implementation of targeted and effective mitigation strategies. View this paper

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10 pages, 230 KiB  
Article
High-Loading-Dose Colistin with Nebulized Administration for Carbapenem-Resistant Acinetobacter baumannii Pneumonia in Critically Ill Patients: A Retrospective Cohort Study
by Wasan Katip, Ajaree Rayanakorn, Chuleegone Sornsuvit, Purida Wientong, Peninnah Oberdorfer, Puntapong Taruangsri and Teerapong Nampuan
Antibiotics 2024, 13(3), 287; https://doi.org/10.3390/antibiotics13030287 - 21 Mar 2024
Viewed by 805
Abstract
Carbapenem-resistant Acinetobacter baumannii (CRAB) infections pose a serious threat, with high morbidity and mortality rates. This retrospective cohort study, conducted at Nakornping Hospital between January 2015 and October 2022, aimed to evaluate the efficacy and safety of a high loading dose (LD) of [...] Read more.
Carbapenem-resistant Acinetobacter baumannii (CRAB) infections pose a serious threat, with high morbidity and mortality rates. This retrospective cohort study, conducted at Nakornping Hospital between January 2015 and October 2022, aimed to evaluate the efficacy and safety of a high loading dose (LD) of colistin combined with nebulized colistin in critically ill patients with CRAB pneumonia. Of the 261 patients included, 95 received LD colistin, and 166 received LD colistin with nebulized colistin. Multivariate Cox regression analysis, adjusted for baseline covariates using inverse probability weighting, showed no significant difference in 30-day survival between patients who received LD colistin and those who received LD colistin with nebulized colistin (adjusted hazard ratio [aHR]: 1.17, 95% confidence interval [CI]: 0.80–1.72, p = 0.418). Likewise, there were no significant differences in clinical response (aHR: 0.93, 95% CI: 0.66–1.31, p = 0.688), microbiological response (aHR: 1.21, 95% CI: 0.85–1.73, p = 0.279), or nephrotoxicity (aHR: 1.14, 95% CI: 0.79–1.64, p = 0.492) between the two treatment groups. No significant adverse events related to nebulized colistin were reported. These findings suggest that the addition of nebulized colistin may not offer additional benefits in terms of 30-day survival, clinical or microbiological response, or nephrotoxicity in these patients. Full article
16 pages, 2328 KiB  
Article
Antifungal and Coagulation Properties of a Copper (I) Oxide Nanopowder Produced by Out-of-Phase Pulsed Sonoelectrochemistry
by Valérie Mancier, Sirine Fattoum, Hélène Haguet, Julie Laloy, Christina Maillet, Sophie C. Gangloff and Jean-Paul Chopart
Antibiotics 2024, 13(3), 286; https://doi.org/10.3390/antibiotics13030286 - 21 Mar 2024
Viewed by 746
Abstract
Copper (I) oxide (cuprite) is a material widely used nowadays, and its versatility is further amplified when it is brought to the nanometric size. Among the possible applications of this nanomaterial, one of the most interesting is that in the medical field. This [...] Read more.
Copper (I) oxide (cuprite) is a material widely used nowadays, and its versatility is further amplified when it is brought to the nanometric size. Among the possible applications of this nanomaterial, one of the most interesting is that in the medical field. This paper presents a cuprite nanopowder study with the aim of employing it in medical applications. With regards to the environmental context, the synthesis used is related to green chemistry since the technique (out-of-phase pulsed electrochemistry) uses few chemical products via electricity consumption and soft conditions of temperature and pressure. After different physico-chemical characterizations, the nanopowder was tested on the Candida albicans to determine its fungicide activity and on human blood to estimate its hemocompatibility. The results show that 2 mg of this nanopowder diluted in 30 µL Sabouraud broth was able to react with Candida albicans. The hemocompatibility tests indicate that for 25 to 100 µg/mL of nanopowder in an aqueous medium, the powder was not toxic for human blood (no hemolysis nor platelet aggregation) but promoted blood coagulation. It appears, therefore, as a potential candidate for the functionalization of matrices for medical applications (wound dressing or operating field, for example). Full article
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20 pages, 1249 KiB  
Review
Antimicrobial and Diagnostic Stewardship of the Novel β-Lactam/β-Lactamase Inhibitors for Infections Due to Carbapenem-Resistant Enterobacterales Species and Pseudomonas aeruginosa
by Stefanos Ferous, Cleo Anastassopoulou, Vassiliki Pitiriga, Georgia Vrioni and Athanasios Tsakris
Antibiotics 2024, 13(3), 285; https://doi.org/10.3390/antibiotics13030285 - 21 Mar 2024
Viewed by 1073
Abstract
Carbapenem-resistant Gram-negative bacterial infections are a major public health threat due to the limited therapeutic options available. The introduction of the new β-lactam/β-lactamase inhibitors (BL/BLIs) has, however, altered the treatment options for such pathogens. Thus, four new BL/BLI combinations—namely, ceftazidime/avibactam, meropenem/vaborbactam, imipenem/relebactam, and [...] Read more.
Carbapenem-resistant Gram-negative bacterial infections are a major public health threat due to the limited therapeutic options available. The introduction of the new β-lactam/β-lactamase inhibitors (BL/BLIs) has, however, altered the treatment options for such pathogens. Thus, four new BL/BLI combinations—namely, ceftazidime/avibactam, meropenem/vaborbactam, imipenem/relebactam, and ceftolozane/tazobactam—have been approved for infections attributed to carbapenem-resistant Enterobacterales species and Pseudomonas aeruginosa. Nevertheless, although these antimicrobials are increasingly being used in place of other drugs such as polymyxins, their optimal clinical use is still challenging. Furthermore, there is evidence that resistance to these agents might be increasing, so urgent measures should be taken to ensure their continued effectiveness. Therefore, clinical laboratories play an important role in the judicious use of these new antimicrobial combinations by detecting and characterizing carbapenem resistance, resolving the presence and type of carbapenemase production, and accurately determining the minimum inhibitor concentrations (MICs) for BL/BLIs. These three targets must be met to ensure optimal BL/BLIs use and prevent unnecessary exposure that could lead to the development of resistance. At the same time, laboratories must ensure that results are interpreted in a timely manner to avoid delays in appropriate treatment that might be detrimental to patient safety. Thus, we herein present an overview of the indications and current applications of the new antimicrobial combinations and explore the diagnostic limitations regarding both carbapenem resistance detection and the interpretation of MIC results. Moreover, we suggest the use of alternative narrower-spectrum antibiotics based on susceptibility testing and present data regarding the effect of synergies between BL/BLIs and other antimicrobials. Finally, in order to address the absence of a standardized approach to using the novel BL/BLIs, we propose a diagnostic and therapeutic algorithm, which can be modified based on local epidemiological criteria. This framework could also be expanded to incorporate other new antimicrobials, such as cefiderocol, or currently unavailable BL/BLIs such as aztreonam/avibactam and cefepime/taniborbactam. Full article
(This article belongs to the Special Issue Feature Reviews on Antibiotics Use and Antimicrobial Stewardship)
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22 pages, 852 KiB  
Article
Antimicrobial Treatment Challenges in the Management of Infective Spondylodiscitis Associated with Hemodialysis: A Comprehensive Review of Literature and Case Series Analysis
by Ioana A. Ratiu, Corina F. Moisa, Laura Țiburcă, Edy Hagi-Islai, Anamaria Ratiu, Gabriel Cristian Bako, Cristian Adrian Ratiu and Liana Stefan
Antibiotics 2024, 13(3), 284; https://doi.org/10.3390/antibiotics13030284 - 20 Mar 2024
Viewed by 899
Abstract
Infective spondylodiscitis (ISD), the infection of vertebral bodies and surrounding tissues, is a rare complication with major impact on the long-term survival of hemodialysis (HD) patients. Although the most frequent etiology is staphylococcal, identifying these pathogens in blood cultures and biopsy cultures [...] Read more.
Infective spondylodiscitis (ISD), the infection of vertebral bodies and surrounding tissues, is a rare complication with major impact on the long-term survival of hemodialysis (HD) patients. Although the most frequent etiology is staphylococcal, identifying these pathogens in blood cultures and biopsy cultures is often difficult. This paper aims to present suitable antibiotic combinations for the treatment of these patients, which is usually challenging in the case of an unidentified pathogen. We presented the therapies applied for 13 HD patients and 19 patients without chronic kidney disease (CKD), diagnosed with ISD between 2013 and 2023 in Bihor County. The percentage of positive blood cultures was low in both groups (30.78% HD vs. 15.78% non-HD). The average length of antibiotic therapy was 5.15 weeks in HD patients and 6.29 weeks in non-HD patients. The use of Carbapenem alone (e.g., Meropenem) for an average of 19.6 days for patients in HD when the pathogen was not identified has proven to be efficient in most cases, similarly to using Vancomycin and Fluoroquinolone/Cephalosporines in combination. Regarding the non-CKD patients, the use of Clindamycin in various combinations for an average of 30.3 days has proven to be efficient in more than 90% of cases of ISD with a nonidentified pathogen. Within 2 years after ISD was diagnosed, 12 of the 13 HD patients passed away, mainly due to cardiovascular causes. Unfortunately, there are no guidelines in the literature concerning the empiric treatment of ISD in the particular case of HD patients. Upon checking the literature on PubMed and Google Scholar, only 10 studies provided relevant data regarding ISD treatment for HD patients. More data about the treatment and evolution of these patients is needed in order to elaborate a truly relevant metanalysis. Full article
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16 pages, 1618 KiB  
Article
One Hundred Explicit Definitions of Potentially Inappropriate Prescriptions of Antibiotics in Hospitalized Older Patients: The Results of an Expert Consensus Study
by Nicolas Baclet, Emmanuel Forestier, Gaëtan Gavazzi, Claire Roubaud-Baudron, Vincent Hiernard, Rozenn Hequette-Ruz, Serge Alfandari, Hugues Aumaître, Elisabeth Botelho-Nevers, Pauline Caraux-Paz, Alexandre Charmillon, Sylvain Diamantis, Thibaut Fraisse, Pierre Gazeau, Maxime Hentzien, Jean-Philippe Lanoix, Marc Paccalin, Alain Putot, Yvon Ruch, Eric Senneville and Jean-Baptiste Beuscartadd Show full author list remove Hide full author list
Antibiotics 2024, 13(3), 283; https://doi.org/10.3390/antibiotics13030283 - 20 Mar 2024
Viewed by 820
Abstract
Background: In geriatrics, explicit criteria for potentially inappropriate prescriptions (PIPs) are useful for optimizing drug use. Objective: To produce an expert consensus on explicit definitions of antibiotic-PIPs for hospitalized older patients. Methods: We conducted a Delphi survey involving French experts on antibiotic stewardship [...] Read more.
Background: In geriatrics, explicit criteria for potentially inappropriate prescriptions (PIPs) are useful for optimizing drug use. Objective: To produce an expert consensus on explicit definitions of antibiotic-PIPs for hospitalized older patients. Methods: We conducted a Delphi survey involving French experts on antibiotic stewardship in hospital settings. During the survey’s rounds, the experts gave their opinion on each explicit definition, and could suggest new definitions. Definitions with a 1-to-9 Likert score of between 7 and 9 from at least 75% of the participants were adopted. The results were discussed during consensus meetings after each round. Results: Of the 155 invited experts, 128 (82.6%) participated in the whole survey: 59 (46%) infectious diseases specialists, 45 (35%) geriatricians, and 24 (19%) other specialists. In Round 1, 65 explicit definitions were adopted and 21 new definitions were suggested. In Round 2, 35 other explicit definitions were adopted. The results were validated during consensus meetings (with 44 participants after Round 1, and 54 after Round 2). Conclusions: The present study is the first to have provided a list of explicit definitions of potentially inappropriate antibiotic prescriptions for hospitalized older patients. It might help to disseminate key messages to prescribers and reduce inappropriate prescriptions of antibiotics. Full article
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10 pages, 694 KiB  
Article
Risk Factors and Outcomes of Community-Acquired Carbapenem-Resistant Klebsiella pneumoniae Infection in Elderly Patients
by Yen-Chou Chen, I-Ting Tsai, Chung-Hsu Lai, Kuo-Hsuan Lin and Yin-Chou Hsu
Antibiotics 2024, 13(3), 282; https://doi.org/10.3390/antibiotics13030282 - 20 Mar 2024
Viewed by 838
Abstract
The increasing prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) infections is a global concern. Elderly patients have a diminished immune response and functional reserve, and are thus more vulnerable to bacterial infection. This study aimed to investigate the risk factors and outcomes in elderly [...] Read more.
The increasing prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) infections is a global concern. Elderly patients have a diminished immune response and functional reserve, and are thus more vulnerable to bacterial infection. This study aimed to investigate the risk factors and outcomes in elderly patients with community-acquired CRKP infections. We performed a retrospective cohort study in a tertiary medical center between 1 January 2021, and 31 December 2021. All elderly patients who visited the emergency department during this period with culture-positive K. pneumoniae were enrolled, and their baseline demographics, laboratory profiles, management strategies, and outcomes were recorded and analyzed. We identified 528 elderly patients with K. pneumonia infection, and the proportion of patients with CRKP infection was 10.2% (54/528). Recent intensive care unit (ICU) admission and prior carbapenem use are independent risk factors for CRKP infection in elderly patients. Compared to patients with carbapenem-sensitive K. pneumoniae infection, those with CRKP infection had a significantly higher risk of adverse outcomes, including ICU care, respiratory failure, septic shock, and 90-day mortality. CRKP infection was also identified as an independent risk factor for 90-day mortality. Clinicians should be aware of the increasing prevalence of CRKP infections in elderly patients and judiciously choose appropriate antibiotics for these patients. Full article
(This article belongs to the Special Issue Antibiotic Resistance and Antimicrobial Use in Elderly Patients)
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15 pages, 2509 KiB  
Article
Assessment of Colistin Heteroresistance among Multidrug-Resistant Klebsiella pneumoniae Isolated from Intensive Care Patients in Europe
by Anouk J. M. M. Braspenning, Sahaya Glingston Rajakani, Adwoa Sey, Mariem El Bounja, Christine Lammens, Youri Glupczynski and Surbhi Malhotra-Kumar
Antibiotics 2024, 13(3), 281; https://doi.org/10.3390/antibiotics13030281 - 20 Mar 2024
Viewed by 877
Abstract
Heteroresistance (HR) to colistin is especially concerning in settings where multi-drug-resistant (MDR) K. pneumoniae are prevalent and empiric use of colistin might lead to treatment failures. This study aimed to assess the frequency of occurrence of colistin HR (CHR) among (MDR) K. pneumoniae [...] Read more.
Heteroresistance (HR) to colistin is especially concerning in settings where multi-drug-resistant (MDR) K. pneumoniae are prevalent and empiric use of colistin might lead to treatment failures. This study aimed to assess the frequency of occurrence of colistin HR (CHR) among (MDR) K. pneumoniae (n = 676) isolated from patients hospitalized in 13 intensive care units (ICUs) in six European countries in a clinical trial assessing the impact of decolonization strategies. All isolates were whole-genome-sequenced and studied for in vitro colistin susceptibility. The majority were colistin-susceptible (CS) (n = 597, MIC ≤ 2 µg/mL), and 79 were fully colistin-resistant (CR) (MIC > 2 µg/mL). A total of 288 CS isolates were randomly selected for population analysis profiling (PAP) to assess CHR prevalence. CHR was detected in 108/288 CS K. pneumoniae. No significant association was found between the occurrence of CHR and country, MIC-value, K-antigen type, and O-antigen type. Overall, 92% (617/671) of the K. pneumoniae were MDR with high prevalence among CS (91%, 539/592) and CR (98.7%, 78/79) isolates. In contrast, the proportion of carbapenemase-producing K. pneumoniae (CP-Kpn) was higher among CR (72.2%, 57/79) than CS isolates (29.3%, 174/594). The proportions of MDR and CP-Kpn were similar among CHR (MDR: 85%, 91/107; CP-Kpn: 29.9%, 32/107) and selected CS isolates (MDR: 84.7%, 244/288; CP-Kpn: 28.1%, 80/285). WGS analysis of PAP isolates showed diverse insertion elements in mgrB or even among technical replicates underscoring the stochasticity of the CHR phenotype. CHR isolates showed high sequence type (ST) diversity (Simpson’s diversity index, SDI: 0.97, in 52 of the 85 STs tested). CR (SDI: 0.85) isolates were highly associated with specific STs (ST101, ST147, ST258/ST512, p ≤ 0.003). The widespread nature of CHR among MDR K. pneumoniae in our study urge the development of rapid HR detection methods to inform on the need for combination regimens. Full article
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12 pages, 423 KiB  
Article
Equivalence Trial of the Non-Bismuth 10-Day Concomitant and 14-Day Hybrid Therapies for Helicobacter pylori Eradication in High Clarithromycin Resistance Areas
by Sotirios D. Georgopoulos, Elias Xirouchakis, Christos Liatsos, Pericles Apostolopoulos, Panagiotis Kasapidis, Beatriz Martinez-Gonzalez, Fotini Laoudi, Maria Stoupaki, Georgios Axiaris, Dionysios Sgouras, Andreas Mentis and Spyridon Michopoulos
Antibiotics 2024, 13(3), 280; https://doi.org/10.3390/antibiotics13030280 - 20 Mar 2024
Viewed by 767
Abstract
Background and aim: We conducted an equivalence trial of quadruple non-bismuth “concomitant” and “hybrid” regimens for H. pylori eradication in a high clarithromycin resistance area. Methods: There were 321 treatment-naïve H. pylori-positive individuals in this multicenter clinical trial randomized to [...] Read more.
Background and aim: We conducted an equivalence trial of quadruple non-bismuth “concomitant” and “hybrid” regimens for H. pylori eradication in a high clarithromycin resistance area. Methods: There were 321 treatment-naïve H. pylori-positive individuals in this multicenter clinical trial randomized to either the hybrid (esomeprazole 40 mg/bid, amoxicillin 1 g/bid for 7 days, then 7 days esomeprazole 40 mg/bid, amoxicillin 1 g/bid, clarithromycin 500 mg/bid, and metronidazole 500 mg/bid) or the concomitant regimen (all medications given concurrently bid for 10 days). Eradication was tested using histology and/or a 13C-urea breath test. Results: The concomitant regimen had 161 patients (90F/71M, mean 54.5 years, 26.7% smokers, 30.4% ulcer) and the hybrid regimen had 160 (80F/80M, mean 52.8 years, 35.6% smokers, 31.2% ulcer). The regimens were equivalent, by intention to treat 85% and 81.8%, (p = 0.5), and per protocol analysis 91.8% and 87.8%, (p = 0.3), respectively. The eradication rate by resistance, between concomitant and hybrid regimens, was in susceptible strains (97% and 97%, p = 0.6), clarithromycin single-resistant strains (86% and 90%, p = 0.9), metronidazole single-resistant strains (96% and 81%, p = 0.1), and dual-resistant strains (70% and 53%, p = 0.5). The side effects were comparable, except for diarrhea being more frequent in the concomitant regimen. Conclusions: A 14-day hybrid regimen is equivalent to a 10-day concomitant regimen currently used in high clarithromycin and metronidazole resistance areas. Both regimens are well tolerated and safe. Full article
(This article belongs to the Section Antibiotic Therapy in Infectious Diseases)
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17 pages, 1763 KiB  
Article
The Home Environment Is a Reservoir for Methicillin-Resistant Coagulase-Negative Staphylococci and Mammaliicocci
by Mari Røken, Stanislav Iakhno, Anita Haug Haaland, Ane Mohn Bjelland and Yngvild Wasteson
Antibiotics 2024, 13(3), 279; https://doi.org/10.3390/antibiotics13030279 - 19 Mar 2024
Viewed by 884
Abstract
Coagulase-negative staphylococci (CoNS) and mammaliicocci are opportunistic human and animal pathogens, often resistant to multiple antimicrobials, including methicillin. Methicillin-resistant CoNS (MRCoNS) have traditionally been linked to hospitals and healthcare facilities, where they are significant contributors to nosocomial infections. However, screenings of non-hospital environments [...] Read more.
Coagulase-negative staphylococci (CoNS) and mammaliicocci are opportunistic human and animal pathogens, often resistant to multiple antimicrobials, including methicillin. Methicillin-resistant CoNS (MRCoNS) have traditionally been linked to hospitals and healthcare facilities, where they are significant contributors to nosocomial infections. However, screenings of non-hospital environments have linked MRCoNS and methicillin-resistant mammaliicocci (MRM) to other ecological niches. The aim of this study was to explore the home environment as a reservoir for MRCoNS and MRM. A total of 33 households, including households with a dog with a methicillin-resistant staphylococcal infection, households with healthy dogs or cats and households without pets, were screened for MRCoNS and MRM by sampling one human, one pet (if present) and the environment. Samples were analyzed by a selective culture-based method, and bacterial species were identified by MALDI-TOF MS and tested for antibiotic susceptibility by the agar disk diffusion method. Following whole-genome sequencing, a large diversity of SCCmec elements and sequence types was revealed, which did not indicate any clonal dissemination of specific strains. Virulome and mobilome analyses indicated a high degree of species specificity. Altogether, this study documents that the home environment is a reservoir for a variety of MRCoNS and MRM regardless of the type of household. Full article
(This article belongs to the Special Issue Antibiotics Resistance in Animals and the Environment)
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17 pages, 2778 KiB  
Article
ApoE Mimetic Peptide COG1410 Kills Mycobacterium smegmatis via Directly Interfering ClpC’s ATPase Activity
by Chun Wang, Yun-Yao Ren, Li-Mei Han, Peng-Cheng Yi, Wei-Xiao Wang, Cai-Yun Zhang, Xiu-Zhen Chen, Ming-Zhe Chi, Apeng Wang, Wei Chen and Chun-Mei Hu
Antibiotics 2024, 13(3), 278; https://doi.org/10.3390/antibiotics13030278 - 19 Mar 2024
Viewed by 709
Abstract
Antimicrobial peptides (AMPs) hold promise as alternatives to combat bacterial infections, addressing the urgent global threat of antibiotic resistance. COG1410, a synthetic peptide derived from apolipoprotein E, has exhibited potent antimicrobial properties against various bacterial strains, including Mycobacterium smegmatis. However, our study [...] Read more.
Antimicrobial peptides (AMPs) hold promise as alternatives to combat bacterial infections, addressing the urgent global threat of antibiotic resistance. COG1410, a synthetic peptide derived from apolipoprotein E, has exhibited potent antimicrobial properties against various bacterial strains, including Mycobacterium smegmatis. However, our study reveals a previously unknown resistance mechanism developed by M. smegmatis against COG1410 involving ClpC. Upon subjecting M. smegmatis to serial passages in the presence of sub-MIC COG1410, resistance emerged. The comparative genomic analysis identified a point mutation in ClpC (S437P), situated within its middle domain, which led to high resistance to COG1410 without compromising bacterial fitness. Complementation of ClpC in mutant restored bacterial sensitivity. In-depth analyses, including transcriptomic profiling and in vitro assays, uncovered that COG1410 interferes with ClpC at both transcriptional and functional levels. COG1410 not only stimulated the ATPase activity of ClpC but also enhanced the proteolytic activity of Clp protease. SPR analysis confirmed that COG1410 directly binds with ClpC. Surprisingly, the identified S437P mutation did not impact their binding affinity. This study sheds light on a unique resistance mechanism against AMPs in mycobacteria, highlighting the pivotal role of ClpC in this process. Unraveling the interplay between COG1410 and ClpC enriches our understanding of AMP-bacterial interactions, offering potential insights for developing innovative strategies to combat antibiotic resistance. Full article
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13 pages, 658 KiB  
Article
Multiple Drug Resistant Streptococcus Strains—An Actual Problem in Pig Farms in Western Romania
by Luminita Costinar, Corina Badea, Adela Marcu, Corina Pascu and Viorel Herman
Antibiotics 2024, 13(3), 277; https://doi.org/10.3390/antibiotics13030277 - 19 Mar 2024
Viewed by 945
Abstract
Streptococci are a type of bacteria that can cause severe illnesses in humans and animals. Some typical species like S. suis, or atypical species like S. porcinus and, S. dysgalactiae subsp. dysgalactiae, can cause infections like septicemia, meningitis, endocarditis, arthritis, and [...] Read more.
Streptococci are a type of bacteria that can cause severe illnesses in humans and animals. Some typical species like S. suis, or atypical species like S. porcinus and, S. dysgalactiae subsp. dysgalactiae, can cause infections like septicemia, meningitis, endocarditis, arthritis, and septic shock. S. suis is considered a newly emerging zoonotic pathogen. Although human streptococcal infection outbreaks are rare, it is appropriate to review the main streptococcal species isolated in pig farms in western Romania, due to the high degree of antibiotic resistance among most isolates commonly used in human treatment. This study examines the resistance patterns of these isolates over 5 years (2018–2023). The research investigated the antimicrobial susceptibility of 267 strains of Streptococcus spp. isolated from pigs, primarily from lung and brain tissues. This report is the first to describe the distribution of atypical Streptococcus species (SDSE, S. porcinus, S. hyovaginalis, S. pluranimalium, S. canis) in Romania, as well as the antibiotic resistance profile of these potentially zoonotic species. It is important to re-evaluate and consider the high rates of resistance of S. suis to tetracyclines, lincosamides, macrolides, and aminoglycosides, as well as the high recovery rates of S. suis from the lungs and brain when treating swine diseases. Full article
(This article belongs to the Special Issue Antibiotics Use in Farms, 2nd Volume)
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15 pages, 4799 KiB  
Article
Sub-MIC Antibiotics Modulate Productions of Outer Membrane Vesicles in Tigecycline-Resistant Escherichia coli
by Qianru Li, Jun Li, Tao He, Xing Ji, Ruicheng Wei, Meiling Yu and Ran Wang
Antibiotics 2024, 13(3), 276; https://doi.org/10.3390/antibiotics13030276 - 19 Mar 2024
Viewed by 911
Abstract
Antimicrobial resistance (AMR) has been recognized as one of the most important crises affecting global human health in the 21st century. Tigecycline is one of the last resort antibiotics for treating severe infections caused by multi-drug resistant Enterobacteriaceae. However, the mobile resistance [...] Read more.
Antimicrobial resistance (AMR) has been recognized as one of the most important crises affecting global human health in the 21st century. Tigecycline is one of the last resort antibiotics for treating severe infections caused by multi-drug resistant Enterobacteriaceae. However, the mobile resistance gene tet(X4), which could mediate high-level tigecycline resistance, was discovered in 2019. The outer membrane vesicle (OMV) has been recognized as a new route for horizontal gene transfer; antimicrobial resistant bacteria also have the ability to secret OMVs, while little is known about the impact of antibiotics on the secretion and characteristics of OMVs from tigecycline resistant bacteria till now. This study aimed to investigate the effects of antibiotics on the production and traits of a tigecycline resistant Escherichia coli strain of 47EC. The results showed that sub-inhibitory (1/2 MIC or 1/4 MIC) concentrations of gentamicin, meropenem, ceftazidime, chloramphenicol, tigecycline, ciprofloxacin, polymycin, rifaximin and mitomycin C could significantly increase the secretion of OMVs (0.713 ± 0.05~6.333 ± 0.15 mg/mL) from E. coli 47EC compared to the respective untreated control (0.709 ± 0.03 mg/mL). In addition, the particle sizes of OMVs were generally larger, and the zeta potential were lower in the antibiotics-treated groups than those of the antibiotic-free group. The copy numbers of the tigecycline resistance gene of tet(X4) in the OMVs of most antimicrobial-treated groups were higher than that of the control group. Moreover, transcriptome analysis on ciprofloxacin-treated E. coli 47EC indicated that the SOS response and prophage activation might participate in the ciprofloxacin-induced OMV formation. In conclusion, the clinical application of antibiotics in treating bacterial infections, especially multi-drug resistant bacteria, might lead to the increased secretion of bacterial OMVs and the enrichment of antimicrobial-resistant genes in the OMVs. Full article
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13 pages, 267 KiB  
Article
Phenotypic and Genotypic Characterization of Pan-Drug-Resistant Klebsiella pneumoniae Isolated in Qatar
by Mazen A. Sid Ahmed, Jemal M. Hamid, Ahmed M. M. Hassan, Sulieman Abu Jarir, Emad Bashir Ibrahim and Hamad Abdel Hadi
Antibiotics 2024, 13(3), 275; https://doi.org/10.3390/antibiotics13030275 - 19 Mar 2024
Viewed by 887
Abstract
In secondary healthcare, carbapenem-resistant Enterobacterales (CREs), such as those observed in Klebsiella pneumoniae, are a global public health priority with significant clinical outcomes. In this study, we described the clinical, phenotypic, and genotypic characteristics of three pan-drug-resistant (PDR) isolates that demonstrated extended [...] Read more.
In secondary healthcare, carbapenem-resistant Enterobacterales (CREs), such as those observed in Klebsiella pneumoniae, are a global public health priority with significant clinical outcomes. In this study, we described the clinical, phenotypic, and genotypic characteristics of three pan-drug-resistant (PDR) isolates that demonstrated extended resistance to conventional and novel antimicrobials. All patients had risk factors for the acquisition of multidrug-resistant organisms, while microbiological susceptibility testing showed resistance to all conventional antimicrobials. Advanced susceptibility testing demonstrated resistance to broad agents, such as ceftazidime-avibactam, ceftolozane–tazobactam, and meropenem–vaborbactam. Nevertheless, all isolates were susceptible to cefiderocol, suggested as one of the novel antimicrobials that demonstrated potent in vitro activity against resistant Gram-negative bacteria, including CREs, pointing toward its potential therapeutic role for PDR pathogens. Expanded genomic studies revealed multiple antimicrobial-resistant genes (ARGs), including blaNMD-5 and blaOXA derivative types, as well as a mutated outer membrane porin protein (OmpK37). Full article
(This article belongs to the Special Issue Antibiotics Use and Therapy in Gram-Negative Bacterial Infection)
9 pages, 631 KiB  
Article
Effect of Inappropriate Treatment in Hospitalized Patients with Pyelonephritis Treated with Cefuroxime: A Cohort Study
by Jorge Alberto Cortés, Claudia Rocío Sierra and Ricardo Sánchez
Antibiotics 2024, 13(3), 274; https://doi.org/10.3390/antibiotics13030274 - 19 Mar 2024
Viewed by 734
Abstract
The aim of this study was to evaluate the effect of inappropriate therapy in adult patients with community-acquired pyelonephritis caused by Escherichia coli receiving empirical treatment with cefuroxime during hospital stay and readmission. A retrospective cohort study was performed. Inappropriate treatment was considered [...] Read more.
The aim of this study was to evaluate the effect of inappropriate therapy in adult patients with community-acquired pyelonephritis caused by Escherichia coli receiving empirical treatment with cefuroxime during hospital stay and readmission. A retrospective cohort study was performed. Inappropriate treatment was considered treatment for a nonsusceptible isolate according to the results of the urine culture. Adjustment for confounding factors was performed with propensity score-derived inverse probability of treatment weighting. Between 2013 and 2020, 747 patients were included, 102 (13.7%) of whom received inappropriate therapy. Compared to appropriate therapy, inappropriate therapy was associated with a shorter length of stay in the adjusted analysis (Hazard Ratio = 0.34; 95% CI = 0.23–0.49). After 735 patients were discharged from the hospital, 66 were readmitted in the following 30 days. In comparison with appropriate therapy, inappropriate antimicrobial therapy was not related to readmission (OR 1.47; 95% CI = 0.35–2.79). Inappropriate therapy was not related to a longer hospital stay or readmission due to pyelonephritis after adjusting for confounders and covariates. Full article
(This article belongs to the Section Antibiotic Therapy in Infectious Diseases)
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25 pages, 886 KiB  
Review
Strategies for Preventing and Treating Oral Mucosal Infections Associated with Removable Dentures: A Scoping Review
by Adriana Barbosa Ribeiro, Pillar Gonçalves Pizziolo, Lorena Mosconi Clemente, Helena Cristina Aguiar, Beatriz de Camargo Poker, Arthur Augusto Martins e Silva, Laís Ranieri Makrakis, Marco Aurelio Fifolato, Giulia Cristina Souza, Viviane de Cássia Oliveira, Evandro Watanabe and Cláudia Helena Lovato da Silva
Antibiotics 2024, 13(3), 273; https://doi.org/10.3390/antibiotics13030273 - 18 Mar 2024
Viewed by 990
Abstract
Oral infections occur due to contact between biofilm rich in Candida albicans formed on the inner surface of complete dentures and the mucosa. This study investigated historical advances in the prevention and treatment of oral mucosal infection and identified gaps in the literature. [...] Read more.
Oral infections occur due to contact between biofilm rich in Candida albicans formed on the inner surface of complete dentures and the mucosa. This study investigated historical advances in the prevention and treatment of oral mucosal infection and identified gaps in the literature. Bibliographic research was conducted, looking at PubMed, Embase, Web of Science, and Scopus, where 935 articles were found. After removing duplicates and excluding articles by reading the title and abstract, 131 articles were selected for full reading and 104 articles were included. Another 38 articles were added from the gray literature. This review followed the PRISMA-ScR guidelines. The historical period described ranges from 1969 to 2023, in which, during the 21st century, in vitro and in vivo studies became more common and, from 2010 to 2023, the number of randomized controlled trials increased. Among the various approaches tested are the incorporation of antimicrobial products into prosthetic materials, the improvement of oral and denture hygiene protocols, the development of synthetic and natural products for the chemical control of microorganisms, and intervention with local or systemic antimicrobial agents. Studies report good results with brushing combined with sodium hypochlorite, and new disinfectant solutions and products incorporated into prosthetic materials are promising. Full article
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13 pages, 730 KiB  
Review
When to Stop Antibiotics in the Critically Ill?
by Nathan D. Nielsen, James T. Dean III, Elizabeth A. Shald, Andrew Conway Morris, Pedro Povoa, Jeroen Schouten and Nicholas Parchim
Antibiotics 2024, 13(3), 272; https://doi.org/10.3390/antibiotics13030272 - 18 Mar 2024
Viewed by 5280
Abstract
Over the past century, antibiotic usage has skyrocketed in the treatment of critically ill patients. There have been increasing calls to establish guidelines for appropriate treatment and durations of antibiosis. Antibiotic treatment, even when appropriately tailored to the patient and infection, is not [...] Read more.
Over the past century, antibiotic usage has skyrocketed in the treatment of critically ill patients. There have been increasing calls to establish guidelines for appropriate treatment and durations of antibiosis. Antibiotic treatment, even when appropriately tailored to the patient and infection, is not without cost. Short term risks—hepatic/renal dysfunction, intermediate effects—concomitant superinfections, and long-term risks—potentiating antimicrobial resistance (AMR), are all possible consequences of antimicrobial administration. These risks are increased by longer periods of treatment and unnecessarily broad treatment courses. Recently, the literature has focused on multiple strategies to determine the appropriate duration of antimicrobial therapy. Further, there is a clinical shift to multi-modal approaches to determine the most suitable timepoint at which to end an antibiotic course. An approach utilising biomarker assays and an inter-disciplinary team of pharmacists, nurses, physicians, and microbiologists appears to be the way forward to develop sound clinical decision-making surrounding antibiotic treatment. Full article
(This article belongs to the Special Issue Antibacterial Resistance and Infection Control in ICU)
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36 pages, 3954 KiB  
Review
Antimicrobial Action Mechanisms of Natural Compounds Isolated from Endophytic Microorganisms
by Farkhod Eshboev, Nilufar Mamadalieva, Pavel A. Nazarov, Hidayat Hussain, Vladimir Katanaev, Dilfuza Egamberdieva and Shakhnoz Azimova
Antibiotics 2024, 13(3), 271; https://doi.org/10.3390/antibiotics13030271 - 18 Mar 2024
Viewed by 1293
Abstract
Infectious diseases are a significant challenge to global healthcare, especially in the face of increasing antibiotic resistance. This urgent issue requires the continuous exploration and development of new antimicrobial drugs. In this regard, the secondary metabolites derived from endophytic microorganisms stand out as [...] Read more.
Infectious diseases are a significant challenge to global healthcare, especially in the face of increasing antibiotic resistance. This urgent issue requires the continuous exploration and development of new antimicrobial drugs. In this regard, the secondary metabolites derived from endophytic microorganisms stand out as promising sources for finding antimicrobials. Endophytic microorganisms, residing within the internal tissues of plants, have demonstrated the capacity to produce diverse bioactive compounds with substantial pharmacological potential. Therefore, numerous new antimicrobial compounds have been isolated from endophytes, particularly from endophytic fungi and actinomycetes. However, only a limited number of these compounds have been subjected to comprehensive studies regarding their mechanisms of action against bacterial cells. Furthermore, the investigation of their effects on antibiotic-resistant bacteria and the identification of biosynthetic gene clusters responsible for synthesizing these secondary metabolites have been conducted for only a subset of these promising compounds. Through a comprehensive analysis of current research findings, this review describes the mechanisms of action of antimicrobial drugs and secondary metabolites isolated from endophytes, antibacterial activities of the natural compounds derived from endophytes against antibiotic-resistant bacteria, and biosynthetic gene clusters of endophytic fungi responsible for the synthesis of bioactive secondary metabolites. Full article
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27 pages, 2648 KiB  
Review
Scientific Rationale and Clinical Basis for Clindamycin Use in the Treatment of Dermatologic Disease
by Maria K. Armillei, Ivan B. Lomakin, James Q. Del Rosso, Ayman Grada and Christopher G. Bunick
Antibiotics 2024, 13(3), 270; https://doi.org/10.3390/antibiotics13030270 - 17 Mar 2024
Viewed by 1154
Abstract
Clindamycin is a highly effective antibiotic of the lincosamide class. It has been widely used for decades to treat a range of skin and soft tissue infections in dermatology and medicine. Clindamycin is commonly prescribed for acne vulgaris, with current practice standards utilizing [...] Read more.
Clindamycin is a highly effective antibiotic of the lincosamide class. It has been widely used for decades to treat a range of skin and soft tissue infections in dermatology and medicine. Clindamycin is commonly prescribed for acne vulgaris, with current practice standards utilizing fixed-combination topicals containing clindamycin that prevent Cutibacterium acnes growth and reduce inflammation associated with acne lesion formation. Certain clinical presentations of folliculitis, rosacea, staphylococcal infections, and hidradenitis suppurativa are also responsive to clindamycin, demonstrating its suitability and versatility as a treatment option. This review describes the use of clindamycin in dermatological practice, the mechanism of protein synthesis inhibition by clindamycin at the level of the bacterial ribosome, and clindamycin’s anti-inflammatory properties with a focus on its ability to ameliorate inflammation in acne. A comparison of the dermatologic indications for similarly utilized antibiotics, like the tetracycline class antibiotics, is also presented. Finally, this review addresses both the trends and mechanisms for clindamycin and antibiotic resistance, as well as the current clinical evidence in support of the continued, targeted use of clindamycin in dermatology. Full article
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18 pages, 7223 KiB  
Article
A Single Dose of Piperacillin Plus Tazobactam Gel as an Adjunct to Professional Mechanical Plaque Removal (PMPR) in Patients with Peri-Implant Mucositis: A 6-Month Double-Blind Randomized Clinical Trial
by Ioana Ilyes, Marius Boariu, Darian Rusu, Vincenzo Iorio-Siciliano, Octavia Vela, Simina Boia, Georgios Kardaras, Petra Șurlin, Horia Calniceanu, Holger Jentsch, Alexandru Lodin and Stefan-Ioan Stratul
Antibiotics 2024, 13(3), 269; https://doi.org/10.3390/antibiotics13030269 - 17 Mar 2024
Viewed by 893
Abstract
Objectives: This randomized, placebo-controlled, double-masked clinical trial aimed to evaluate the clinical and microbiological efficacy of professional mechanical plaque removal (PMPR) with or without adjunctive application of piperacillin plus tazobactam gel in the treatment of peri-implant mucositis (PiM) for up to 6 months. [...] Read more.
Objectives: This randomized, placebo-controlled, double-masked clinical trial aimed to evaluate the clinical and microbiological efficacy of professional mechanical plaque removal (PMPR) with or without adjunctive application of piperacillin plus tazobactam gel in the treatment of peri-implant mucositis (PiM) for up to 6 months. Materials and Methods: The study included 31 patients with peri-implant mucositis (bleeding on probing (BoP) > 1 at at least one site at baseline, absence of peri-implant bone loss compared with a previous radiograph). After randomized assignment to test and control groups, patients received full-mouth supragingival scaling with or without piperacillin plus tazobactam gel. Clinical examination was performed at baseline and after 3 and 6 months, and a microbiological examination was performed at baseline and after 3 months. Results: After six months, both treatment modalities resulted in significant reductions and improvements in clinical parameters at the implant sites. Neither study group achieved a complete resolution of PiM (i.e., BoP ≤ 1 per implant). The number of implants with BoP decreased statistically significantly between subsequent time points (p < 0.001) in both the test and the control group. Significant BoP differences (p = 0.039) were observed between groups at 6 months (difference to baseline) following therapy. Conclusions: Within the limitations of the present study, the single use of a slow-release, locally applied antibiotic combination of piperacillin and tazobactam gel, adjunctive to PMPR, showed an improvement in clinical variable of implants diagnosed with PiM. The adjunctive treatment resulted in higher BoP reduction when compared to the control, but no significant differences were observed regarding the changes in other clinical and microbiological parameters. Full article
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14 pages, 710 KiB  
Review
Rethinking Hidradenitis Suppurativa Management: Insights into Bacterial Interactions and Treatment Evolution
by Faith D. Huynh, Giovanni Damiani and Christopher G. Bunick
Antibiotics 2024, 13(3), 268; https://doi.org/10.3390/antibiotics13030268 - 17 Mar 2024
Viewed by 1320
Abstract
Hidradenitis suppurativa (HS), or acne inversa, is a chronic inflammatory dermatological condition characterized by painful and recurrent nodules and purulent abscesses. HS can have a devastating impact on the quality of life of patients. This condition is commonly localized to the axilla, groin, [...] Read more.
Hidradenitis suppurativa (HS), or acne inversa, is a chronic inflammatory dermatological condition characterized by painful and recurrent nodules and purulent abscesses. HS can have a devastating impact on the quality of life of patients. This condition is commonly localized to the axilla, groin, perineal, and inframammary regions, and can develop fistulas and sinus tracts over time. Its pathogenesis remains elusive and is best characterized at the moment as multi-factorial. Additionally, questions remain about the role of cutaneous dysbiosis as a primary HS trigger or as a secondary perturbation due to HS inflammation. This article features works in relation to HS and its interplay with bacterial microflora. We address current treatment approaches and their impact on HS-related bacteria, as well as areas of therapeutic innovation. In the future, disease-modifying or remittive therapy will likely combine an advanced/targeted anti-inflammatory approach with one that effectively modulates cutaneous and deep tissue dysbiosis. Full article
(This article belongs to the Section Antibiotic Therapy in Infectious Diseases)
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12 pages, 822 KiB  
Review
Helicobacter pylori in Inflammatory Bowel Diseases: Active Protagonist or Innocent Bystander?
by Elisabetta Bretto, Simone Frara, Angelo Armandi, Gian Paolo Caviglia, Giorgio Maria Saracco, Elisabetta Bugianesi, Demis Pitoni and Davide Giuseppe Ribaldone
Antibiotics 2024, 13(3), 267; https://doi.org/10.3390/antibiotics13030267 - 17 Mar 2024
Viewed by 918
Abstract
Helicobacter pylori (H. pylori) infection is a prominent entity within human infectious diseases which cause chronic gastritis, peptic ulcers, gastric malignancies, and extragastric disorders. Its persistent colonization can lead to a systemic inflammatory cascade, potentially instigating autoimmune responses and contributing to [...] Read more.
Helicobacter pylori (H. pylori) infection is a prominent entity within human infectious diseases which cause chronic gastritis, peptic ulcers, gastric malignancies, and extragastric disorders. Its persistent colonization can lead to a systemic inflammatory cascade, potentially instigating autoimmune responses and contributing to the pathogenesis of autoimmune diseases. While the specific etiopathogenesis of inflammatory bowel diseases (IBDs) is still unknown, it is widely recognized that immunological, genetic, and environmental factors are implicated. Various bacterial and viral pathogens have been implicated in the pathogenesis of IBDs. Numerous studies suggest a correlation between H. pylori infection and IBDs. While subject to debate, this link suggests that the bacterium’s presence somehow impacts the progression of IBDs by modifying the diversity of the gut microbiota, consequently altering local chemical profiles and disrupting the pattern of gut immune response. However, epidemiological evidence indicates a protective role of H. pylori infection against the onset of autoimmune diseases. Additionally, laboratory findings demonstrate H. pylori’s capacity to promote immune tolerance and restrict inflammatory reactions. The aim of this review is to elucidate the proposed mechanisms and confounding factors that underlie the potential association between H. pylori infection and IBDs. Full article
(This article belongs to the Special Issue Pathogenesis, Diagnosis and Treatment of H. pylori Infection)
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11 pages, 269 KiB  
Article
Identification and Clinical Characteristics of Community-Acquired Acinetobacter baumannii in Patients Hospitalized for Moderate or Severe COVID-19 in Peru
by Wilmer Silva-Caso, Giancarlo Pérez-Lazo, Miguel Angel Aguilar-Luis, Adriana Morales-Moreno, José Ballena-López, Fernando Soto-Febres, Johanna Martins-Luna, Luis J. Del Valle, Sungmin Kym, Deysi Aguilar-Luis, Dayana Denegri-Hinostroza and Juana del Valle-Mendoza
Antibiotics 2024, 13(3), 266; https://doi.org/10.3390/antibiotics13030266 - 16 Mar 2024
Viewed by 1140
Abstract
Acinetobacter baumannii has been described as a cause of serious community-acquired infections in tropical countries. Currently, its implications when simultaneously identified with other pathogens are not yet adequately understood. A descriptive study was conducted on hospitalized patients with a diagnosis of moderate/severe SARS-CoV-2-induced [...] Read more.
Acinetobacter baumannii has been described as a cause of serious community-acquired infections in tropical countries. Currently, its implications when simultaneously identified with other pathogens are not yet adequately understood. A descriptive study was conducted on hospitalized patients with a diagnosis of moderate/severe SARS-CoV-2-induced pneumonia confirmed via real-time RT-PCR. Patients aged > 18 years who were admitted to a specialized COVID-19 treatment center in Peru were selected for enrollment. A. baumannii was detected via the PCR amplification of the blaOXA-51 gene obtained from nasopharyngeal swabs within 48 h of hospitalization. A total of 295 patients with COVID-19 who met the study inclusion criteria were enrolled. A. baumannii was simultaneously identified in 40/295 (13.5%) of COVID-19-hospitalized patients. Demographic data and comorbidities were comparable in both Acinetobacter-positive and -negative subgroups. However, patients identified as being infected with Acinetobacter were more likely to have received outpatient antibiotics prior to hospitalization, had a higher requirement for high-flow nasal cannula and a higher subjective incidence of fatigue, and were more likely to develop Acinetobacter-induced pneumonia during hospitalization. Conclusions: The group in which SARS-CoV-2 and A. baumannii were simultaneously identified had a higher proportion of fatigue, a higher frequency of requiring a high-flow cannula, and a higher proportion of superinfection with the same microorganism during hospitalization. Full article
20 pages, 1281 KiB  
Article
The Clinical Efficacy of Adding Ceftazidime/Avibactam to Standard Therapy in Treating Infections Caused by Carbapenem-Resistant Klebsiella pneumonia with blaOXA-48-like Genes
by Al Maamon R. Abu Jaber, Bilgen Basgut, Ali Abdullah Hawan, Ali Amer Al Shehri, Sultan Ahmad AlKahtani, Nehad J. Ahmed and Abdikarim Abdi
Antibiotics 2024, 13(3), 265; https://doi.org/10.3390/antibiotics13030265 - 16 Mar 2024
Viewed by 781
Abstract
Ceftazidime/avibactam (CAZ-AVI) is FDA-approved for managing infections caused by resistant gram-negative bacilli, particularly infections via carbapenem-resistant Enterobacterales pathogens. The clinical data are still limited, particularly those in Saudi Arabia. The present study is a retrospective cohort study that was carried out at the [...] Read more.
Ceftazidime/avibactam (CAZ-AVI) is FDA-approved for managing infections caused by resistant gram-negative bacilli, particularly infections via carbapenem-resistant Enterobacterales pathogens. The clinical data are still limited, particularly those in Saudi Arabia. The present study is a retrospective cohort study that was carried out at the Armed Forces Hospital in the southern region of Saudi Arabia to compare the clinical and microbiological outcomes for CAZ-AVI-treated patients as monotherapy and as an add-on to standard therapy for carbapenem-resistant Klebsiella pneumonia (CRKP) OXA-48 infections to those treated with standard drugs. The study included CRKP OXA-48-like infected patients who were administered antibiotics for more than seven days from 1 August 2018 to May 2023. Patients’ baseline characteristics and demography were extracted from the clinical records, and their clinical/microbiology efficiencies were assessed as per the corresponding definitions. Univariate and multivariate logistic regressions were conducted to identify the potential independent variable for CAZ-AVI efficiency. A total of 114 patient files were included for the evaluation. Among these patients, 64 used CAZ-AVI combined with standard therapy and were included in the intervention group, and 50 of them used standard therapy and were included in the comparative group. Following analysis, CAZ-AVI’s clinical success was 42.2% (p = 0.028), while the intervention versus comparative groups showed decreased 30-day all-cause mortality (50.0% versus 70.0%; p = 0.036) and infection recurrence (7.8% versus 24.0%; p = 0.019), as well as substantially increased rates of microbial eradication (68.8% versus 42.0%; p = 0.007). CAZ-AVI add-on therapy rather than monotherapy showed statistically significant favored clinical and microbial outcomes over the standard therapy. Furthermore, sex (female %), ICU admission, and fever were negatively associated with patients’ 30-day all-cause mortality, serving as independent negative factors. Only fever, CRP bio levels, inotropes, and ICU admissions were significant predictors influencing the CAZ-AVI’s clinical efficiency. The duration of CAZ-AVI therapy positively influenced CAZ-AVI’s microbial eradication, while both WBC counts and fever experiences were negative predictors. This study shows the effective usage of CAZ-AVI against CRKP OXA-48-like infections. The influencing independent variables depicted here should recommend that clinicians individualize the CAZ-AVI dose based on co-existing risk factors to achieve optimal survival and efficacy. Prospective multicenter and randomized control studies are recommended, with individualized CAZ-AVI precision administration implemented based on patients’ characteristics. Full article
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14 pages, 2026 KiB  
Article
Generation and Characterization of Stable Small Colony Variants of USA300 Staphylococcus aureus in RAW 264.7 Murine Macrophages
by Dalida Bivona, Carmelo Bonomo, Lorenzo Colombini, Paolo G. Bonacci, Grete F. Privitera, Giuseppe Caruso, Filippo Caraci, Francesco Santoro, Nicolò Musso, Dafne Bongiorno, Francesco Iannelli and Stefania Stefani
Antibiotics 2024, 13(3), 264; https://doi.org/10.3390/antibiotics13030264 - 16 Mar 2024
Viewed by 914
Abstract
Intracellular survival and immune evasion are typical features of staphylococcal infections. USA300 is a major clone of methicillin-resistant S. aureus (MRSA), a community- and hospital-acquired pathogen capable of disseminating throughout the body and evading the immune system. Carnosine is an endogenous dipeptide characterized [...] Read more.
Intracellular survival and immune evasion are typical features of staphylococcal infections. USA300 is a major clone of methicillin-resistant S. aureus (MRSA), a community- and hospital-acquired pathogen capable of disseminating throughout the body and evading the immune system. Carnosine is an endogenous dipeptide characterized by antioxidant and anti-inflammatory properties acting on the peripheral (macrophages) and tissue-resident (microglia) immune system. In this work, RAW 264.7 murine macrophages were infected with the USA300 ATCC BAA-1556 S. aureus strain and treated with 20 mM carnosine and/or 32 mg/L erythromycin. Stable small colony variant (SCV) formation on blood agar medium was obtained after 48 h of combined treatment. Whole genome sequencing of the BAA-1556 strain and its stable derivative SCVs when combining Illumina and nanopore technologies revealed three single nucleotide differences, including a nonsense mutation in the shikimate kinase gene aroK. Gene expression analysis showed a significant up-regulation of the uhpt and sdrE genes in the stable SCVs compared with the wild-type, likely involved in adaptation to the intracellular milieu. Full article
(This article belongs to the Section Antibiotic Therapy in Infectious Diseases)
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12 pages, 3418 KiB  
Article
Biofilm Development by Mycobacterium avium Complex Clinical Isolates: Effect of Clarithromycin in Ultrastructure
by Arij Akir, Abrar Senhaji-Kacha, Maria Carmen Muñoz-Egea, Jaime Esteban and John Jairo Aguilera-Correa
Antibiotics 2024, 13(3), 263; https://doi.org/10.3390/antibiotics13030263 - 16 Mar 2024
Viewed by 717
Abstract
Background: The Mycobacterium avium complex includes the commonest non-tuberculous mycobacteria associated with human infections. These infections have been associated with the production of biofilms in many cases, but there are only a few studies about biofilms produced by the species included in this [...] Read more.
Background: The Mycobacterium avium complex includes the commonest non-tuberculous mycobacteria associated with human infections. These infections have been associated with the production of biofilms in many cases, but there are only a few studies about biofilms produced by the species included in this group. Methods: Three collection strains (M. avium ATCC25291, M. intracellulare ATCC13950, and M. chimaera DSM756), three clinically significant strains (647, 657, and 655), and three clinically non-significant ones (717, 505, and 575) of each species were included. The clinical significance of the clinical isolates was established according to the internationally accepted criteria. The biofilm ultrastructure was studied by Confocal-Laser Scanning Microscopy by using BacLight Live–Dead and Nile Red stains. The viability, covered surface, height, and relative autofluorescence were measured in several images/strain. The effect of clarithromycin was studied by using the technique described by Muñoz-Egea et al. with modifications regarding incubation time. The study included clarithromycin in the culture medium at a concentration achievable in the lungs (11.3 mg/L), using one row of wells as the control without antibiotics. The bacterial viability inside the biofilm is expressed as a percentage of viable cells. The differences between the different parameters of the biofilm ultrastructure were analyzed by using the Kruskal–Wallis test. The correlation between bacterial viability in the biofilm and treatment time was evaluated by using Spearman’s rank correlation coefficient (ρ). Results: The strains showed differences between them with all the studied parameters, but neither a species-specific pattern nor a clinical-significance-specific pattern were detected. For the effect of clarithromycin, the viability of the bacteria contained in the biofilm was inversely proportional to the exposure time of the biofilm (ρ > −0.3; p-value < 0.05), excluding two M. chimaera strains (M. chimaera DSM756 and 575), which showed a weak positive correlation with treatment time (0.2 < ρ < 0.39; p-value < 0.05). Curiously, despite a clarithromycin treatment of 216 h, the percentage of the biofilm viability of the strains evaluated here was not less than 40% at best (M. avium 717). Conclusions: All the M. avium complex strains studied can form biofilm in vitro, but the ultrastructural characteristics between them suggest that these are strain-specific characteristics unrelated to the species or the clinical significance. The clarithromycin effect on MAC species is biofilm-age/time-of-treatment-dependent and appears to be strain-specific while being independent of the clinical significance of the strain. Full article
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13 pages, 1071 KiB  
Article
Post-COVID-19 Pandemic Rebound of Macrolide-Resistant Mycoplasma pneumoniae Infection: A Descriptive Study
by Fan-Fan Xing, Kelvin Hei-Yeung Chiu, Chao-Wen Deng, Hai-Yan Ye, Lin-Lin Sun, Yong-Xian Su, Hui-Jun Cai, Simon Kam-Fai Lo, Lei Rong, Jian-Liang Chen, Vincent Chi-Chung Cheng, David Christopher Lung, Siddharth Sridhar, Jasper Fuk-Woo Chan, Ivan Fan-Ngai Hung and Kwok-Yung Yuen
Antibiotics 2024, 13(3), 262; https://doi.org/10.3390/antibiotics13030262 - 15 Mar 2024
Viewed by 1050
Abstract
The rebound characteristics of respiratory infections after lifting pandemic control measures were uncertain. From January to November 2023, patients presenting at a teaching hospital were tested for common respiratory viruses and Mycoplasma pneumoniae using a combination of antigen, nucleic acid amplification, and targeted [...] Read more.
The rebound characteristics of respiratory infections after lifting pandemic control measures were uncertain. From January to November 2023, patients presenting at a teaching hospital were tested for common respiratory viruses and Mycoplasma pneumoniae using a combination of antigen, nucleic acid amplification, and targeted next-generation sequencing (tNGS) tests. The number and rate of positive tests per month, clinical and microbiological characteristics were analyzed. A rapid rebound of SARS-CoV-2 was followed by a slower rebound of M. pneumoniae, with an interval of 5 months between their peaks. The hospitalization rate was higher, with infections caused by respiratory viruses compared to M. pneumoniae. Though the pediatric hospitalization rate of respiratory viruses (66.1%) was higher than that of M. pneumoniae (34.0%), the 4094 cases of M. pneumoniae within 6 months posed a huge burden on healthcare services. Multivariate analysis revealed that M. pneumoniae-infected adults had more fatigue, comorbidities, and higher serum C-reactive protein, whereas children had a higher incidence of other respiratory pathogens detected by tNGS or pathogen-specific PCR, fever, and were more likely to be female. A total of 85% of M. pneumoniae-positive specimens had mutations detected at the 23rRNA gene, with 99.7% showing A2063G mutation. Days to defervescence were longer in those not treated by effective antibiotics and those requiring a change in antibiotic treatment. A delayed but significant rebound of M. pneumoniae was observed after the complete relaxation of pandemic control measures. No unusual, unexplained, or unresponsive cases of respiratory infections which warrant further investigation were identified. Full article
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20 pages, 340 KiB  
Review
Current Therapeutic Approaches for Multidrug-Resistant and Extensively Drug-Resistant Acinetobacter baumannii Infections
by Petros Rafailidis, Periklis Panagopoulos, Christos Koutserimpas and George Samonis
Antibiotics 2024, 13(3), 261; https://doi.org/10.3390/antibiotics13030261 - 15 Mar 2024
Viewed by 1523
Abstract
The treatment of Acinetobacter baumannii infections remains a challenge for physicians worldwide in the 21st century. The bacterium possesses a multitude of mechanisms to escape the human immune system. The consequences of A. baumannii infections on morbidity and mortality, as well on financial [...] Read more.
The treatment of Acinetobacter baumannii infections remains a challenge for physicians worldwide in the 21st century. The bacterium possesses a multitude of mechanisms to escape the human immune system. The consequences of A. baumannii infections on morbidity and mortality, as well on financial resources, remain dire. Furthermore, A. baumannii superinfections have also occurred during the COVID-19 pandemic. While prevention is important, the antibiotic armamentarium remains the most essential factor for the treatment of these infections. The main problem is the notorious resistance profile (including resistance to carbapenems and colistin) that this bacterium exhibits. While newer beta lactam/beta-lactamase inhibitors have entered clinical practice, with excellent results against various infections due to Enterobacteriaceae, their contribution against A. baumannii infections is almost absent. Hence, we have to resort to at least one of the following, sulbactam, polymyxins E or B, tigecycline or aminoglycosides, against multidrug-resistant (MDR) and extensively drug-resistant (XDR) A. baumannii infections. Furthermore, the notable addition of cefiderocol in the fight against A. baumannii infections represents a useful addition. We present herein the existing information from the last decade regarding therapeutic advances against MDR/XDR A. baumannii infections. Full article
20 pages, 4652 KiB  
Review
Role of β-Lactamase Inhibitors as Potentiators in Antimicrobial Chemotherapy Targeting Gram-Negative Bacteria
by Song Zhang, Xinyu Liao, Tian Ding and Juhee Ahn
Antibiotics 2024, 13(3), 260; https://doi.org/10.3390/antibiotics13030260 - 15 Mar 2024
Viewed by 1191
Abstract
Since the discovery of penicillin, β-lactam antibiotics have commonly been used to treat bacterial infections. Unfortunately, at the same time, pathogens can develop resistance to β-lactam antibiotics such as penicillins, cephalosporins, monobactams, and carbapenems by producing β-lactamases. Therefore, a combination of β-lactam antibiotics [...] Read more.
Since the discovery of penicillin, β-lactam antibiotics have commonly been used to treat bacterial infections. Unfortunately, at the same time, pathogens can develop resistance to β-lactam antibiotics such as penicillins, cephalosporins, monobactams, and carbapenems by producing β-lactamases. Therefore, a combination of β-lactam antibiotics with β-lactamase inhibitors has been a promising approach to controlling β-lactam-resistant bacteria. The discovery of novel β-lactamase inhibitors (BLIs) is essential for effectively treating antibiotic-resistant bacterial infections. Therefore, this review discusses the development of innovative inhibitors meant to enhance the activity of β-lactam antibiotics. Specifically, this review describes the classification and characteristics of different classes of β-lactamases and the synergistic mechanisms of β-lactams and BLIs. In addition, we introduce potential sources of compounds for use as novel BLIs. This provides insights into overcoming current challenges in β-lactamase-producing bacteria and designing effective treatment options in combination with BLIs. Full article
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13 pages, 2164 KiB  
Article
Detection of Extended-Spectrum Beta-Lactamase (ESBL)-Producing Enterobacteriaceae from Diseased Broiler Chickens in Lusaka District, Zambia
by Chikwanda Chileshe, Misheck Shawa, Nelson Phiri, Joseph Ndebe, Cynthia Sipho Khumalo, Chie Nakajima, Masahiro Kajihara, Hideaki Higashi, Hirofumi Sawa, Yasuhiko Suzuki, Walter Muleya and Bernard Mudenda Hang’ombe
Antibiotics 2024, 13(3), 259; https://doi.org/10.3390/antibiotics13030259 - 15 Mar 2024
Viewed by 955
Abstract
Poultry products in Zambia form an integral part of the human diet in many households, as they are cheap and easy to produce. The burden of poultry diseases has, however, remained a major challenge. Growing consumer demand for poultry products in Zambia has [...] Read more.
Poultry products in Zambia form an integral part of the human diet in many households, as they are cheap and easy to produce. The burden of poultry diseases has, however, remained a major challenge. Growing consumer demand for poultry products in Zambia has resulted in non-prudent antimicrobial use on farms, intending to prevent and treat poultry diseases for growth optimisation and maximising profits. This cross-sectional study aimed to identify the different types of bacteria causing diseases in chickens in Lusaka and to detect the extended-spectrum lactamase (ESBL)-encoding genes. We collected 215 samples from 91 diseased chickens at three post-mortem facilities and screened them for Gram-negative bacteria. Of these samples, 103 tested positive for various clinically relevant Enterobacteriaceae, including Enterobacter (43/103, 41.7%), Escherichia coli (20/103, 19.4%), Salmonella (10/103, 9.7%), and Shigella (8/103, 7.8%). Other isolated bacteria included Yersinia, Morganella, Proteus, and Klebsiella, which accounted for 21.4%. E. coli, Enterobacter, Salmonella, and Shigella were subjected to antimicrobial susceptibility testing. The results revealed that E. coli, Enterobacter, and Shigella were highly resistant to tetracycline, ampicillin, amoxicillin, and trimethoprim-sulfamethoxazole, while Salmonella showed complete susceptibility to all tested antibiotics. The observed resistance patterns correlated with antimicrobial usage estimated from sales data from a large-scale wholesale and retail company. Six (6/14, 42.9%) E. coli isolates tested positive for blaCTX-M, whilst eight (8/14, 57.1%) Enterobacter samples tested positive for blaTEM. Interestingly, four (4/6, 66.7%) of the E. coli isolates carrying blaCTX-M-positive strains were also positive for blaTEM. Sanger sequencing of the PCR products revealed that five (5/6, 83.3%) of the abovementioned isolates possessed the blaCTX-M-15 allele. The results suggest the presence of potentially pathogenic ESBL-producing Enterobacteriaceae in poultry, threatening public health. Full article
(This article belongs to the Special Issue Use of Antibiotics in Animals and Antimicrobial Resistance)
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15 pages, 2994 KiB  
Article
Intrapulmonary and Systemic Pharmacokinetics of Colistin Following Nebulization of Low-Dose Colistimethate Sodium in Patients with Ventilator-Associated Pneumonia Caused by Carbapenem-Resistant Acinetobacter baumannii
by Dong-Hwan Lee, Shin-Young Kim, Yong-Kyun Kim, So-Young Jung, Ji-Hoon Jang, Hang-Jea Jang and Jae-Ha Lee
Antibiotics 2024, 13(3), 258; https://doi.org/10.3390/antibiotics13030258 - 14 Mar 2024
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Abstract
Colistimethate sodium (CMS) nebulization is associated with reduced systemic toxicity compared to intravenous injection, with potentially enhanced clinical efficacy. This study aimed to assess the pharmacokinetic (PK) properties of colistin during low-dose CMS nebulization in patients with ventilator-associated pneumonia (VAP) caused by carbapenem-resistant [...] Read more.
Colistimethate sodium (CMS) nebulization is associated with reduced systemic toxicity compared to intravenous injection, with potentially enhanced clinical efficacy. This study aimed to assess the pharmacokinetic (PK) properties of colistin during low-dose CMS nebulization in patients with ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii. A nonlinear mixed-effects modeling approach was applied to develop population PK models for colistin in both epithelial lining fluid (ELF) and plasma. Twenty patients participated, and 80 ELF and 100 plasma samples were used for model development. Median colistin concentrations measured in ELF were 614-fold, 408-fold, and 250-fold higher than in plasma at 1, 3, and 5 h, respectively. Time courses in both ELF and plasma were best described by a one-compartment model with a Weibull absorption process. When the final model was simulated, the maximum free concentration and area under the free colistin concentration–time curve at steady state over 24 h in the plasma were approximately 1/90 and 1/50 of the corresponding values in ELF at steady state, respectively. For an A. baumannii MIC of 1 mg/L, inhaling 75 mg of CMS at 6 h intervals was deemed appropriate, with dose adjustments needed for MICs exceeding 2 mg/L. Using a nebulizer for CMS resulted in a notably higher exposure of colistin in the ELF than plasma, indicating the potential of nebulization to reduce systemic toxicity while effectively treating VAP. Full article
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