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Antibiotics
Volume 13
Issue 6
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Antibiotics, Volume 13, Issue 6 (June 2024) – 101 articles

Cover Story (view full-size image): Carbapenemase-producing Enterobacter cloacae complex strains are increasingly identified in hospital-acquired infections. MLST ST182 has been sporadically reported among Enterobacter hormaechei strains, and recently, outbreaks of blaNDM-producing ST182 clonal strains have emerged. We aimed to investigate the presence of ST182 and explore its evolution and modes of blaNDM acquisition. A phylogenetic analysis of 646 MLST STs identified among 4685 E. hormaechei WGS assemblies deposited in public repositories was performed, as well as in silico comparative and phylogenomic analyses for 55 WGS assemblies of ST182. Our findings showed that ST182 E. hormaechei strains have been identified in the past decade worldwide; 54.5% of them carried diverse blaNDM genetic structures, suggesting the recent acquisition of the blaNDM alleles. View this paper
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18 pages, 638 KiB  
Review
Supra- and Subgingival Microbiome in Gingivitis and Impact of Biofilm Control: A Comprehensive Review
by Margarita Iniesta, Viviane Vasconcelos, Mariano Sanz and David Herrera
Antibiotics 2024, 13(6), 571; https://doi.org/10.3390/antibiotics13060571 - 20 Jun 2024
Viewed by 339
Abstract
This comprehensive review aimed (1) to characterize the sub- and supragingival microbiome in patients with biofilm-induced gingivitis (including experimental gingivitis), (2) to assess its stability and evolution over time, and (3) to assess the impact of biofilm control measures on this stability. An [...] Read more.
This comprehensive review aimed (1) to characterize the sub- and supragingival microbiome in patients with biofilm-induced gingivitis (including experimental gingivitis), (2) to assess its stability and evolution over time, and (3) to assess the impact of biofilm control measures on this stability. An electronic search of the MEDLINE®/PubMed® database until December 2023 was conducted. NCBI Taxonomy, eHOMD 16S rRNA Reference Sequence, and Tree Version 15.23 databases were used to standardize taxonomic nomenclature. Out of 89 papers initially retrieved, 14 studies were finally included: 11 using experimental gingivitis as a model and three randomized clinical trials evaluating the impact of biofilm control measures. Among them, five characterized the subgingival microbiome, nine the supragingival microbiome, and one both the sub- and supragingival microbiome. In addition, five studies evaluated the effect of toothpaste, and four studies evaluated the effect of mouth rinses. The diversity and structure of the microbiome differed significantly between patients with periodontal health and those with biofilm-induced gingivitis (including experimental gingivitis). Those differences were not reversed through conventional oral hygiene measures. Specific antiseptic agents, especially if delivered as mouth rinses, may have an impact on the supra- and subgingival microbiome in gingivitis. Full article
(This article belongs to the Special Issue Periodontitis: Prevention and Treatment)
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13 pages, 1668 KiB  
Review
Robinsoniella peoriensis Infections in Humans—A Narrative Review
by Petros Ioannou, Stella Baliou and Diamantis Kofteridis
Antibiotics 2024, 13(6), 570; https://doi.org/10.3390/antibiotics13060570 - 20 Jun 2024
Viewed by 426
Abstract
Robinsoniella peoriensis is a Gram-positive, strictly anaerobic, spore-forming, rod-shaped bacterium belonging to the phylum Firmicutes and the family Lachnospiraceae. Until now, R. peoriensis is the only species of its genus. It was first isolated in 2003 during a study into the flora of lagoons [...] Read more.
Robinsoniella peoriensis is a Gram-positive, strictly anaerobic, spore-forming, rod-shaped bacterium belonging to the phylum Firmicutes and the family Lachnospiraceae. Until now, R. peoriensis is the only species of its genus. It was first isolated in 2003 during a study into the flora of lagoons and manure pits. Given the rarity of this microorganism and the sparse information in the literature about its way of transmission, the way to diagnose its infections and identify it in the microbiology laboratory, and its public health relevance, the present study aimed to identify all the published cases of Robinsoniella, describe the epidemiological, clinical, and microbiological characteristics, and provide information about its antimicrobial resistance, treatment, and outcomes. A narrative review was performed based on a Pubmed/Medline and Scopus databases search. In total, 14 studies provided data on 17 patients with infections by Robinsoniella. The median age of patients was 63 years and 47% were male. The most common types of infection were bone and joint infections, bacteremia, infective endocarditis, and peritonitis. The only isolated species was R. peoriensis, and antimicrobial resistance to clindamycin was 50%, but was 0% to the combination of piperacillin with tazobactam, aminopenicillin with a beta-lactamase inhibitor, and metronidazole which were the most commonly used antimicrobials for the treatment of these infections. The overall mortality depends on the type of infection and is notable only for bacteremia, while all other infections had an optimal outcome. Future studies should better assess these infections’ clinical and epidemiological characteristics and the mechanisms of the antimicrobial resistance of this microorganism from a mechanistic and genetic perspective. Full article
(This article belongs to the Special Issue Epidemiology, Clinical Microbiology and Antimicrobial Therapy: A Shared Effort against Infectious Diseases)
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14 pages, 525 KiB  
Article
Impact of Appropriate Empirical Antibiotic Treatment on the Clinical Response of Septic Patients in Intensive Care Unit: A Single-Center Observational Study
by Mateo Tićac, Tanja Grubić Kezele and Marina Bubonja Šonje
Antibiotics 2024, 13(6), 569; https://doi.org/10.3390/antibiotics13060569 - 19 Jun 2024
Viewed by 405
Abstract
The appropriate antibiotic treatment of patients with bacterial sepsis in the intensive care unit (ICU) remains a challenge. Considering that current international guidelines recommend 7 days of antibiotic therapy as sufficient for most severe infections, our primary outcome was a comparison of clinical [...] Read more.
The appropriate antibiotic treatment of patients with bacterial sepsis in the intensive care unit (ICU) remains a challenge. Considering that current international guidelines recommend 7 days of antibiotic therapy as sufficient for most severe infections, our primary outcome was a comparison of clinical response to initial empirical therapy on day 7 and mortality between two groups of septic patients—with appropriate (AEAT) and inappropriate (IEAT) empirical antibiotic therapy according to the in vitro sensitivity of bacteria detected in a blood culture (BC). Adult patients admitted to the ICU between 2020 and 2023, who were diagnosed with sepsis according to the Sequential Organ Failure Assessment (SOFA) score ≥ 2 in association with a suspected or documented infection, were selected for the study. Of the 418 patients, 149 (35.6%) died within 7 days. Although the AEAT group had a lower mortality rate (30.3% vs. 34.2%) and better clinical improvement (52.8% vs. 47.4%) on day 7 after starting empirical antibiotic therapy, there was no significant difference. A causative organism was isolated from BCs in 30% of septic patients, with gram-negative bacteria (GNB) predominating in 60% of cases, and multidrug-resistant (MDR) or extensively drug-resistant (XDR) bacteria predominantly detected in the BCs of the IEAT group. Although the AEAT group had slightly worse clinical characteristics at the onset of sepsis than the IEAT group, the AEAT group showed faster improvement on days 7 and 14 of sepsis. In this retrospective cross-sectional study, the AEAT group was associated with better clinical response at day 7 after sepsis onset and lower mortality, but without a significant difference. Comorbidities and the type of bacterial pathogen should also be taken into account as they can also contribute to the prediction of the final outcome. These results demonstrate the importance of daily assessment of clinical factors to more accurately predict the clinical outcome of a septic patient. Full article
(This article belongs to the Special Issue Infections and Sepsis in the Intensive Care Unit)
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16 pages, 1426 KiB  
Review
Essential Oils against Candida auris—A Promising Approach for Antifungal Activity
by Adam Kowalczyk
Antibiotics 2024, 13(6), 568; https://doi.org/10.3390/antibiotics13060568 - 19 Jun 2024
Viewed by 579
Abstract
The emergence of Candida auris as a multidrug-resistant fungal pathogen represents a significant global health challenge, especially given the growing issue of antifungal drug resistance. This review aims to illuminate the potential of essential oils (EOs), which are volatile plant secretions containing complex [...] Read more.
The emergence of Candida auris as a multidrug-resistant fungal pathogen represents a significant global health challenge, especially given the growing issue of antifungal drug resistance. This review aims to illuminate the potential of essential oils (EOs), which are volatile plant secretions containing complex mixtures of chemicals, as alternative antifungal agents to combat C. auris, thus combining traditional insights with contemporary scientific findings to address this critical health issue. A systematic literature review was conducted using the PubMed, Scopus, and Web of Science databases from 2019 to 2024, and using the Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) protocol to identify relevant studies on the antifungal efficacy of EOs or their components against C. auris. Of the 90 articles identified, 16 were selected for detailed review. The findings highlight the diverse mechanisms of action of EOs and their components, such as disrupting fungal cell membranes, inducing the production of reactive oxygen species (ROS), and impeding biofilm formation, suggesting that some of them may be as effective as, or better than, traditional antifungal drugs while potentially limiting the development of resistance. However, issues such as variability in the composition of EOs and a paucity of clinical trials have been identified as significant obstacles. In conclusion, EOs and their active ingredients are emerging as viable candidates for creating effective treatments for C. auris, underscoring their importance as alternative or complementary antifungal agents in the face of increasing drug resistance. The call for future research underscores the need for clinical trials and standardization to unlock the full antifungal potential of EOs against C. auris. Full article
(This article belongs to the Special Issue Effect of Antimicrobials on Fungal Biofilms)
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11 pages, 368 KiB  
Article
Diagnostic Accuracy of Urine Dipsticks for Urinary Tract Infection Diagnosis during Pregnancy: A Retrospective Cohort Study
by Dominique E. Werter, Caroline Schneeberger, Suzanne E. Geerlings, Christianne J. M. de Groot, Eva Pajkrt and Brenda M. Kazemier
Antibiotics 2024, 13(6), 567; https://doi.org/10.3390/antibiotics13060567 - 19 Jun 2024
Viewed by 385
Abstract
Objective: Urinary tract infections (UTIs) represent the most prevalent infections among pregnant women. Many pregnant women experience frequent voiding or lower abdominal pain during pregnancy due to physiologic changes. Due to the possible consequences of a UTI in pregnancy, pregnant women are more [...] Read more.
Objective: Urinary tract infections (UTIs) represent the most prevalent infections among pregnant women. Many pregnant women experience frequent voiding or lower abdominal pain during pregnancy due to physiologic changes. Due to the possible consequences of a UTI in pregnancy, pregnant women are more often tested for UTIs. This study aimed to assess the diagnostic accuracy of dipsticks in diagnosing UTIs in pregnant women while using the urine culture as the reference standard. Study design: This was a retrospective cohort study, conducted at two academic hospitals in the Netherlands among pregnant women. Pseudonymized data were collected from patient files. The results of the urine dipstick and the urine culture in pregnant women were linked. Additionally, nitrofurantoin prescriptions were linked to culture results. A positive urine culture was considered the reference test for a UTI. Results: Between 1 January 2017 and 28 February 2021, a total of 718 urine samples with leukocyte esterase dipstick results within 24 h of the urine culture were analyzed. Of these samples, a nitrite dipstick result was also available in 337 cases. Only 6.8% of the 718 urine samples yielded positive cultures. The sensitivity and specificity of leukocyte esterase were 75.5% and 40.4%, respectively; for nitrite, 72.0% sensitivity and 73.4% specificity were found. When at least one of the two tests was positive, the sensitivity and specificity were 92.0% and 27.9%, respectively. When both tests were positive, the sensitivity and specificity were 52.0% and 82.7%, respectively. In only 16.8% of the women to whom nitrofurantoin was prescribed, the urine cultures returned positive using a cut-off of 105 colony forming units/mL. Conclusion: The diagnostic performance of leukocyte esterase, nitrite, or their combination in clinical practice is lower than previously reported in study settings among pregnant women. A significant proportion of women treated with nitrofurantoin were found to have no UTI, suggesting potential over-prescription based on dipstick test results. Healthcare providers should be aware of this reduced performance in clinical practice and carefully weigh the risks of antibiotic treatment by suspicion of a UTI against the possibility of delayed treatment awaiting culture results in individual patients. Full article
(This article belongs to the Special Issue Antimicrobial Prescribing and Antimicrobial Use in Healthcare Settings)
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15 pages, 1785 KiB  
Article
Exploring Prior Antibiotic Exposure Characteristics for COVID-19 Hospital Admission Patients: OpenSAFELY
by Ya-Ting Yang, David Wong, Xiaomin Zhong, Ali Fahmi, Darren M. Ashcroft, Kieran Hand, Jon Massey, Brian Mackenna, Amir Mehrkar, Sebastian Bacon, Ben Goldacre, Victoria Palin and Tjeerd van Staa
Antibiotics 2024, 13(6), 566; https://doi.org/10.3390/antibiotics13060566 - 18 Jun 2024
Viewed by 629
Abstract
Previous studies have demonstrated the association between antibiotic use and severe COVID-19 outcomes. This study aimed to explore detailed antibiotic exposure characteristics among COVID-19 patients. Using the OpenSAFELY platform, which integrates extensive health data and covers 40% of the population in England, the [...] Read more.
Previous studies have demonstrated the association between antibiotic use and severe COVID-19 outcomes. This study aimed to explore detailed antibiotic exposure characteristics among COVID-19 patients. Using the OpenSAFELY platform, which integrates extensive health data and covers 40% of the population in England, the study analysed 3.16 million COVID-19 patients with at least two prior antibiotic prescriptions. These patients were compared to up to six matched controls without hospitalisation records. A machine learning model categorised patients into ten groups based on their antibiotic exposure history over the three years before their COVID-19 diagnosis. The study found that for COVID-19 patients, the total number of prior antibiotic prescriptions, diversity of antibiotic types, broad-spectrum antibiotic prescriptions, time between first and last antibiotics, and recent antibiotic use were associated with an increased risk of severe COVID-19 outcomes. Patients in the highest decile of antibiotic exposure had an adjusted odds ratio of 4.8 for severe outcomes compared to those in the lowest decile. These findings suggest a potential link between extensive antibiotic use and the risk of severe COVID-19. This highlights the need for more judicious antibiotic prescribing in primary care, primarily for patients with higher risks of infection-related complications, which may better offset the potential adverse effects of repeated antibiotic use. Full article
(This article belongs to the Section Antibiotic Therapy in Infectious Diseases)
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45 pages, 4169 KiB  
Review
Non-Canonical Aspects of Antibiotics and Antibiotic Resistance
by Carlos F. Amábile-Cuevas and Sofia Lund-Zaina
Antibiotics 2024, 13(6), 565; https://doi.org/10.3390/antibiotics13060565 - 17 Jun 2024
Viewed by 465
Abstract
The understanding of antibiotic resistance, one of the major health threats of our time, is mostly based on dated and incomplete notions, especially in clinical contexts. The “canonical” mechanisms of action and pharmacodynamics of antibiotics, as well as the methods used to assess [...] Read more.
The understanding of antibiotic resistance, one of the major health threats of our time, is mostly based on dated and incomplete notions, especially in clinical contexts. The “canonical” mechanisms of action and pharmacodynamics of antibiotics, as well as the methods used to assess their activity upon bacteria, have not changed in decades; the same applies to the definition, acquisition, selective pressures, and drivers of resistance. As a consequence, the strategies to improve antibiotic usage and overcome resistance have ultimately failed. This review gathers most of the “non-canonical” notions on antibiotics and resistance: from the alternative mechanisms of action of antibiotics and the limitations of susceptibility testing to the wide variety of selective pressures, lateral gene transfer mechanisms, ubiquity, and societal factors maintaining resistance. Only by having a “big picture” view of the problem can adequate strategies to harness resistance be devised. These strategies must be global, addressing the many aspects that drive the increasing prevalence of resistant bacteria aside from the clinical use of antibiotics. Full article
(This article belongs to the Special Issue Horizontal Gene Transfer (HGT): Key to the Multi-Antibiotic Resistance (MAR) Crisis)
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14 pages, 1049 KiB  
Article
Activity of Aztreonam/Avibactam and Recently Approved β-Lactamase Inhibitor Combinations against Enterobacterales and Pseudomonas aeruginosa from Intensive Care Unit and Non-Intensive Care Unit Patients
by Helio S. Sader, Rodrigo E. Mendes, John H. Kimbrough, Cory M. Hubler and Mariana Castanheira
Antibiotics 2024, 13(6), 564; https://doi.org/10.3390/antibiotics13060564 - 17 Jun 2024
Viewed by 769
Abstract
We evaluated the activities of aztreonam/avibactam and recently approved β-lactamase inhibitor combinations (BLICs) to compare the antimicrobial susceptibility patterns of Enterobacterales and Pseudomonas aeruginosa isolated from intensive care unit (ICU) and non-ICU patients. Clinical isolates (1/patient) were consecutively collected from 72 United States [...] Read more.
We evaluated the activities of aztreonam/avibactam and recently approved β-lactamase inhibitor combinations (BLICs) to compare the antimicrobial susceptibility patterns of Enterobacterales and Pseudomonas aeruginosa isolated from intensive care unit (ICU) and non-ICU patients. Clinical isolates (1/patient) were consecutively collected from 72 United States medical centres in 2020–2022 and susceptibility tested by broth microdilution. The results for 5421 isolates from ICU patients were analysed and compared to those for 20,649 isolates from non-ICU patients. Isolates from ventilator-associated pneumonia patients were analysed separately. Aztreonam/avibactam inhibited 100.0%/>99.9% Enterobacterales and 100.0%/98.3% of carbapenem-resistant Enterobacterales (CRE) from ICU/non-ICU patients at ≤8 mg/L, respectively. The CRE susceptibility rates were 88.5%/82.9% for ceftazidime/avibactam, 82.1%/81.2% for meropenem/vaborbactam, and 78.2%/72.6% for imipenem/relebactam among ICU/non-ICU isolates. Among the P. aeruginosa isolates from ICU/non-ICU patients, the susceptibility rates were 96.3%/97.6% for ceftazidime/avibactam, 97.2/98.4% for ceftolozane/tazobactam, 97.1%/98.0% for imipenem/relebactam, 77.8%/84.6% for piperacillin/tazobactam, and 76.9%/85.8% for meropenem; aztreonam/avibactam inhibited 78.0%/81.9% of P. aeruginosa at ≤8 mg/L. In summary, lower susceptibility rates were observed among ICU than non-ICU isolates. Aztreonam/avibactam exhibited potent in vitro activity and broad-spectrum activity against Enterobacterales from ICU and non-ICU patients, including CRE and isolates non-susceptible to newer BLICs. Against P. aeruginosa, aztreonam/avibactam showed a spectrum of activity comparable to that of piperacillin/tazobactam, meropenem, and ceftazidime. Full article
(This article belongs to the Section Novel Antimicrobial Agents)
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11 pages, 1025 KiB  
Article
Biphasic Medium Using Nicotinamide for Detection of Pyrazinamide Resistance in Mycobacterium tuberculosis
by Waraporn Thuansuwan, Charoen Chuchottaworn, Chie Nakajima, Yasuhiko Suzuki and Nuntaree Chaichanawongsaroj
Antibiotics 2024, 13(6), 563; https://doi.org/10.3390/antibiotics13060563 - 16 Jun 2024
Viewed by 623
Abstract
Reliable drug susceptibility testing of pyrazinamide (PZA) is technically difficult, since PZA activity is pH sensitive. The aim of this study was to evaluate a biphasic medium assay (BMA) for the reliable detection of PZA resistance in Mycobacterium tuberculosis (MTB) using nicotinamide (NIC) [...] Read more.
Reliable drug susceptibility testing of pyrazinamide (PZA) is technically difficult, since PZA activity is pH sensitive. The aim of this study was to evaluate a biphasic medium assay (BMA) for the reliable detection of PZA resistance in Mycobacterium tuberculosis (MTB) using nicotinamide (NIC) as a surrogate for PZA and identifying the appropriate cut-off value for the assay. The PZA susceptibility of 122 multidrug-resistant tuberculosis (MDR-TB) isolates and 39 drug-susceptible tuberculosis (DS-TB) isolates was examined using the BMA with NIC at four different concentrations (250, 500, 1000, and 2000 mg/L) and comparing the results with results from the BACTEC MGIT 960 reference method. Out of 122 MDR-TB isolates, 40 were identified as resistant by the BACTEC MGIT 960 system, of which 92.5% contained mutations within their pncA gene plus promoter region. A minimum inhibitory concentration of NIC ≥ 1000 mg/L was used as the cut-off concentration to define resistance in correlation with the MGIT 960 outcomes. NIC-BMA had a sensitivity of 90.91%, a specificity of 100%, and an accuracy of 97.52% compared with the MGIT 960 method. NIC-BMA is a promising assay to screen PZA resistance in microbiological laboratories without automation or advanced molecular instruments. Full article
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12 pages, 582 KiB  
Review
Cellulosimicrobium Infections in Humans—A Narrative Review
by Petros Ioannou, Alexandra Vorria and George Samonis
Antibiotics 2024, 13(6), 562; https://doi.org/10.3390/antibiotics13060562 - 16 Jun 2024
Viewed by 448
Abstract
Cellulosimicrobium species (formerly known as Oerskovia) are Gram-positive filamentous bacteria in the family Promicromonosporaceae and are more commonly found in sewage and soil. The present study aimed to identify all the published cases of Cellulosimicrobium species infections in the literature, describe the [...] Read more.
Cellulosimicrobium species (formerly known as Oerskovia) are Gram-positive filamentous bacteria in the family Promicromonosporaceae and are more commonly found in sewage and soil. The present study aimed to identify all the published cases of Cellulosimicrobium species infections in the literature, describe the epidemiological, clinical, and microbiological characteristics, and provide data regarding its antimicrobial resistance, treatment, and outcomes. A narrative review was performed based on a PubMed and Scopus database search. In total, 38 studies provided data on 40 patients with infections by these species. The median age of patients was 52.5 years, and 55% were male. The most common infection types were bacteremia, infective endocarditis (IE), osteoarticular infections, peritoneal dialysis-associated peritonitis, and endophthalmitis. Antimicrobial resistance to vancomycin and the combination of trimethoprim and sulfamethoxazole was minimal, and vancomycin was the most commonly used antimicrobial for treating these infections. Overall mortality was minimal for all infections, except for bacteremia and IE, which carried high mortality rates. Full article
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13 pages, 3645 KiB  
Article
Screening of Klebsiella pneumoniae subsp. pneumoniae Strains with Multi-Drug Resistance and Virulence Profiles Isolated from an Italian Hospital between 2020 and 2023
by Valentina Dimartino, Carolina Venditti, Francesco Messina, Silvia D’Arezzo, Marina Selleri, Ornella Butera, Carla Nisii, Alessandra Marani, Alessia Arcangeli, Roberta Gaziano, Terenzio Cosio, Pietro Scanzano and Carla Fontana
Antibiotics 2024, 13(6), 561; https://doi.org/10.3390/antibiotics13060561 - 15 Jun 2024
Viewed by 608
Abstract
Klebsiella pneumoniae strains that are resistant to multiple drugs (KPMDRs), which are often acquired in hospital settings and lead to healthcare-associated infections, pose a serious public health threat, as does hypervirulent K. pneumoniae (hvKp), which can also cause serious infections in otherwise healthy [...] Read more.
Klebsiella pneumoniae strains that are resistant to multiple drugs (KPMDRs), which are often acquired in hospital settings and lead to healthcare-associated infections, pose a serious public health threat, as does hypervirulent K. pneumoniae (hvKp), which can also cause serious infections in otherwise healthy individuals. The widespread and often unnecessary use of antibiotics seen during the recent COVID-19 pandemic has exacerbated the challenges posed by antibiotic resistance in clinical settings. There is growing concern that hypervirulent (hvKp) strains may acquire genes that confer antimicrobial resistance, thus combining an MDR profile with their increased ability to spread to multiple body sites, causing difficult-to-treat infections. This study aimed to compare resistance and virulence profiles in KPC-3-producing K. pneumoniae isolates collected over four years (2020–2023). A genome-based surveillance of all MDR CRE-K. pneumoniae was used to identify genetic differences and to characterize the virulence and resistance profiles. Our results provide a picture of the evolution of resistance and virulence genes and contribute to avoiding the possible spread of isolates with characteristics of multi-drug resistance and increased virulence, which are thought to be one of the main global challenges to public health, within our hospital. Full article
(This article belongs to the Special Issue Epidemiology, Clinical Microbiology and Antimicrobial Therapy: A Shared Effort against Infectious Diseases)
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8 pages, 770 KiB  
Article
Ciprofloxacin Concentrations 100-Fold Lower than the MIC Can Select for Ciprofloxacin Resistance in Neisseria subflava: An In Vitro Study
by Zina Gestels, Saïd Abdellati, Chris Kenyon and Sheeba Santhini Manoharan-Basil
Antibiotics 2024, 13(6), 560; https://doi.org/10.3390/antibiotics13060560 - 14 Jun 2024
Viewed by 500
Abstract
Neisseria gonorrhoeae can acquire antimicrobial resistance (AMR) through horizontal gene transfer (HGT) from other Neisseria spp. such as commensals like Neisseria subflava. Low doses of antimicrobials in food could select for AMR in N. subflava, which could then be transferred to N. [...] Read more.
Neisseria gonorrhoeae can acquire antimicrobial resistance (AMR) through horizontal gene transfer (HGT) from other Neisseria spp. such as commensals like Neisseria subflava. Low doses of antimicrobials in food could select for AMR in N. subflava, which could then be transferred to N. gonorrhoeae. In this study, we aimed to determine the lowest concentration of ciprofloxacin that can induce ciprofloxacin resistance (minimum selection concentration—MSC) in a N. subflava isolate (ID-Co000790/2, a clinical isolate collected from a previous community study conducted at ITM). In this study, Neisseria subflava was serially passaged on gonococcal (GC) medium agar plates containing ciprofloxacin concentrations ranging from 1:100 to 1:10,000 below its ciprofloxacin MIC (0.006 µg/mL) for 6 days. After 6 days of serial passaging at ciprofloxacin concentrations of 1/100th of the MIC, 24 colonies emerged on the plate containing 0.06 µg/mL ciprofloxacin, which corresponds to the EUCAST breakpoint for N. gonorrhoeae. Their ciprofloxacin MICs were between 0.19 to 0.25 µg/mL, and whole genome sequencing revealed a missense mutation T91I in the gyrA gene, which has previously been found to cause reduced susceptibility to fluoroquinolones. The N. subflava MSCde novo was determined to be 0.06 ng/mL (0.00006 µg/mL), which is 100×-fold lower than the ciprofloxacin MIC. The implications of this finding are that the low concentrations of fluoroquinolones found in certain environmental samples, such as soil, river water, and even the food we eat, may be able to select for ciprofloxacin resistance in N. subflava. Full article
(This article belongs to the Special Issue Challenges and Emerging Strategies to Tackle the Global Burden of Antimicrobial Resistance)
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11 pages, 624 KiB  
Review
Ewingella americana Infections in Humans—A Narrative Review
by Petros Ioannou, Stella Baliou and Diamantis Kofteridis
Antibiotics 2024, 13(6), 559; https://doi.org/10.3390/antibiotics13060559 - 14 Jun 2024
Viewed by 459
Abstract
Ewingella americana is a Gram-negative rod that belongs to the order Enterobacterales and the family Yersiniaceae and was first identified in 1983 from 10 clinical strains in the United States of America. The present study aimed to identify all the published cases of [...] Read more.
Ewingella americana is a Gram-negative rod that belongs to the order Enterobacterales and the family Yersiniaceae and was first identified in 1983 from 10 clinical strains in the United States of America. The present study aimed to identify all the published cases of E. americana in the literature, describe the epidemiological, clinical, and microbiological characteristics, and provide data regarding its antimicrobial resistance, treatment, and outcomes. A narrative review was performed based on a PubMed and Scopus databases search. In total, 16 studies provided data on 19 patients with infections by E. americana. The median age of the patients was 55 years, and 47.4% were male. The most common infections were those of the bloodstream, the respiratory tract, and the peritoneal cavity. Antimicrobial resistance to cephalosporins, aminoglycosides, and the combination of trimethoprim with sulfamethoxazole was minimal, and these were the most commonly used antimicrobials for treating these infections. No included study provided information on the genetic or molecular mechanism of this pathogen’s antimicrobial resistance. The overall mortality was minimal, with only one patient with bacteremia succumbing to the infection. Further studies are needed to better understand this microorganism, its pathogenic potential in humans, and the genetic and molecular mechanisms underlying its antimicrobial resistance, for which very little evidence exists to date. Full article
(This article belongs to the Special Issue Epidemiology, Diagnosis and Antimicrobial Treatment of Hospital-Acquired Infections)
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12 pages, 1942 KiB  
Article
Influence of CO2 and Dust on the Survival of Non-Resistant and Multi-Resistant Airborne E. coli Strains
by Viktoria Agarwal, Elena Abd El, Silvia Giulia Danelli, Elena Gatta, Dario Massabò, Federico Mazzei, Benedikt Meier, Paolo Prati, Virginia Vernocchi and Jing Wang
Antibiotics 2024, 13(6), 558; https://doi.org/10.3390/antibiotics13060558 - 14 Jun 2024
Viewed by 516
Abstract
The airborne transmission of bacterial pathogens poses a significant challenge to public health, especially with the emergence of antibiotic-resistant strains. This study investigated environmental factors influencing the survival of airborne bacteria, focusing on the effects of different carbon dioxide (CO2) and [...] Read more.
The airborne transmission of bacterial pathogens poses a significant challenge to public health, especially with the emergence of antibiotic-resistant strains. This study investigated environmental factors influencing the survival of airborne bacteria, focusing on the effects of different carbon dioxide (CO2) and dust concentrations. The experiments were conducted in an atmospheric simulation chamber using the non-resistant wild-type E. coli K12 (JM109) and a multi-resistant variant (JM109-pEC958). Different CO2 (100 ppm, 800 ppm, 3000 ppm) and dust concentrations (250 µg m−3, 500 µg m−3, 2000 µg m−3) were tested to encompass a wide range of CO2 and dust levels. The results revealed that JM109-pEC958 exhibited greater resilience to high CO2 and dust concentrations compared to its non-resistant counterpart. At 3000 ppm CO2, the survival rate of JM109 was significantly reduced, while the survival rate of JM109-pEC958 remained unaffected. At the dust concentration of 250 µg m−3, JM109 exhibited significantly reduced survival, whereas JM109-pEC958 did not. When the dust concentration was increased to 500 and 2000 µg m−3, even the JM109-pEC958 experienced substantially reduced survival rates, which were still significantly higher than those of its non-resistant counterpart at these concentrations. These findings suggest that multi-resistant E. coli strains possess mechanisms enabling them to endure extreme environmental conditions better than non-resistant strains, potentially involving regulatory genes or efflux pumps. The study underscores the importance of understanding bacterial adaptation strategies to develop effective mitigation approaches against antibiotic-resistant bacteria in atmospheric environments. Overall, this study provides valuable insights into the interplay between environmental stressors and bacterial survival, serving as a foundational step towards elucidating the adaptation mechanisms of multi-resistant bacteria and informing strategies for combating antibiotic resistance in the atmosphere. Full article
(This article belongs to the Special Issue Antibiotics and Environment − Research and Development toward the One Health Approach)
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20 pages, 2083 KiB  
Review
Tackling Carbapenem Resistance and the Imperative for One Health Strategies—Insights from the Portuguese Perspective
by Inês Mó and Gabriela Jorge da Silva
Antibiotics 2024, 13(6), 557; https://doi.org/10.3390/antibiotics13060557 - 14 Jun 2024
Viewed by 642
Abstract
Carbapenemases, a class of enzymes specialized in the hydrolysis of carbapenems, represent a significant threat to global public health. These enzymes are classified into different Ambler’s classes based on their active sites, categorized into classes A, D, and B. Among the most prevalent [...] Read more.
Carbapenemases, a class of enzymes specialized in the hydrolysis of carbapenems, represent a significant threat to global public health. These enzymes are classified into different Ambler’s classes based on their active sites, categorized into classes A, D, and B. Among the most prevalent types are IMI/NMC-A, KPC, VIM, IMP, and OXA-48, commonly associated with pathogenic species such as Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The emergence and dissemination of carbapenemase-producing bacteria have raised substantial concerns due to their ability to infect humans and animals (both companion and food-producing) and their presence in environmental reservoirs. Adopting a holistic One Health approach, concerted efforts have been directed toward devising comprehensive strategies to mitigate the impact of antimicrobial resistance dissemination. This entails collaborative interventions, highlighting proactive measures by global organizations like the World Health Organization, the Center for Disease Control and Prevention, and the Food and Agriculture Organization. By synthesizing the evolving landscape of carbapenemase epidemiology in Portugal and tracing the trajectory from initial isolated cases to contemporary reports, this review highlights key factors driving antibiotic resistance, such as antimicrobial use and healthcare practices, and underscores the imperative for sustained vigilance, interdisciplinary collaboration, and innovative interventions to curb the escalating threat posed by antibiotic-resistant pathogens. Finally, it discusses potential alternatives and innovations aimed at tackling carbapenemase-mediated antibiotic resistance, including new therapies, enhanced surveillance, and public awareness campaigns. Full article
(This article belongs to the Section Mechanism and Evolution of Antibiotic Resistance)
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20 pages, 1614 KiB  
Systematic Review
Characteristics of Nontyphoid Salmonella Isolated from Human, Environmental, Animal, and Food Samples in Burkina Faso: A Systematic Review and Meta-Analysis
by Kuan Abdoulaye Traore, Abdoul Rachid Aboubacar-Paraiso, Soutongnooma Caroline Bouda, Jean Bienvenue Ouoba, Assèta Kagambèga, Pierre Roques and Nicolas Barro
Antibiotics 2024, 13(6), 556; https://doi.org/10.3390/antibiotics13060556 - 13 Jun 2024
Viewed by 531
Abstract
Salmonella is one of the world’s leading causes of zoonotic and foodborne illnesses. Recently, antimicrobial resistance (AMR) has become one of the most critical challenges to public health and food safety. Herein, we employed a meta-analysis to determine the pooled prevalence and spatiotemporal [...] Read more.
Salmonella is one of the world’s leading causes of zoonotic and foodborne illnesses. Recently, antimicrobial resistance (AMR) has become one of the most critical challenges to public health and food safety. Herein, we employed a meta-analysis to determine the pooled prevalence and spatiotemporal distribution of serovars and antimicrobial resistance in NTS in Burkina Faso. To find eligible articles, a comprehensive literature search of PubMed, African Journals Online, ScienceDirect, Google Scholar, and the gray literature (university libraries) in Burkina was conducted for the period from 2008 to 2020. Studies meeting the inclusion criteria were selected and assessed for risk of bias. To assess the temporal and spatial relationships between serotypes and resistant strains from humans, animals, food, and the environment, a random-effects statistical model meta-analysis was carried out using the Comprehensive Meta-Analysis Version 3.0 program. The NTS prevalence rates were 4.6% (95% CI: 3–7) and 20.1% (95% CI: 6.6–47.4) in humans and animals, respectively, and 16.8% (95% CI: 10.5–25.8) and 15.6% (95% CI: 8.2–27.5) in food and the environment, respectively. Most NTS serovars were S. Derby, reported both in food and animals, and S. Typhimurium, reported in humans, while S. Croft II, S. Jodpur II, and S. Kentucky were the most prevalent in the environment. NTS isolates were highly resistant to erythromycin, amoxicillin, cefixime, and cephalothin, with a pooled prevalence of multidrug resistance of 29% (95% CI: 14.5–49.5). The results of this review show a high diversity of Salmonella serotypes, as well as high antibiotic resistance in Salmonella isolates from animal, human, food, and environmental samples in Burkina, calling for a consolidated “One Health” approach to better understand the drivers of pathogen emergence, spread, and antimicrobial resistance, as well as the formulation of intervention measures needed to limit the risk associated with the disease. Full article
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21 pages, 2525 KiB  
Article
Mechanistic Study of Antimicrobial Effectiveness of Cyclic Amphipathic Peptide [R4W4] against Methicillin-Resistant Staphylococcus aureus Clinical Isolates
by Ajayi David Akinwale, Keykavous Parang, Rakesh Kumar Tiwari and Jason Yamaki
Antibiotics 2024, 13(6), 555; https://doi.org/10.3390/antibiotics13060555 - 13 Jun 2024
Viewed by 590
Abstract
Antimicrobial peptides (AMPs) are being explored as a potential strategy to combat antibiotic resistance due to their ability to reduce susceptibility to antibiotics. This study explored whether the [R4W4] peptide mode of action is bacteriostatic or bactericidal using modified [...] Read more.
Antimicrobial peptides (AMPs) are being explored as a potential strategy to combat antibiotic resistance due to their ability to reduce susceptibility to antibiotics. This study explored whether the [R4W4] peptide mode of action is bacteriostatic or bactericidal using modified two-fold serial dilution and evaluating the synergism between gentamicin and [R4W4] against Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA) by a checkered board assay. [R4W4] exhibited bactericidal activity against bacterial isolates (MBC/MIC ≤ 4), with a synergistic effect with gentamicin against E. coli (FICI = 0.3) but not against MRSA (FICI = 0.75). Moreover, we investigated the mechanism of action of [R4W4] against MRSA by applying biophysical assays to evaluate zeta potential, cytoplasmic membrane depolarization, and lipoteichoic acid (LTA) binding affinity. [R4W4] at a 16 mg/mL concentration stabilized the zeta potential of MRSA −31 ± 0.88 mV to −8.37 mV. Also, [R4W4] at 2 × MIC and 16 × MIC revealed a membrane perturbation process associated with concentration-dependent effects. Lastly, in the presence of BODIPY-TR-cadaverine (BC) fluorescence dyes, [R4W4] exhibited binding affinity to LTA comparable with melittin, the positive control. In addition, the antibacterial activity of [R4W4] against MRSA remained unchanged in the absence and presence of LTA, with an MIC of 8 µg/mL. Therefore, the [R4W4] mechanism of action is deemed bactericidal, involving interaction with bacterial cell membranes, causing concentration-dependent membrane perturbation. Additionally, after 30 serial passages, there was a modest increment of MRSA strains resistant to [R4W4] and a change in antibacterial effectiveness MIC [R4W4] and vancomycin by 8 and 4 folds with a slight change in Levofloxacin MIC 1 to 2 µg/mL. These data suggest that [R4W4] warrants further consideration as a potential AMP. Full article
(This article belongs to the Special Issue The Role of Antimicrobial Peptides in Tackling Antimicrobial Resistance)
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18 pages, 2594 KiB  
Article
Genetic and Phenotypic Changes Related to the Development of mec-Independent Oxacillin Non-Susceptibility in ST8 Staphylococcus aureus Recovered after Antibiotic Therapy in a Patient with Bacteremia
by Sabrina Di Gregorio, Gabriela Weltman, Carolina Fabbri, Silvina Fernández, Soledad Zárate, Jorgelina Smayevsky, Pablo Power, Josefina Campos, Leticia Irene Llarrull and Marta Mollerach
Antibiotics 2024, 13(6), 554; https://doi.org/10.3390/antibiotics13060554 - 13 Jun 2024
Viewed by 553
Abstract
The mec-independent oxacillin non-susceptible S. aureus (MIONSA) strains represent a great clinical challenge, as they are not easily detected and can lead to treatment failure. However, the responsible molecular mechanisms are still very little understood. Here, we studied four clinical ST8-MSSA-t024 [...] Read more.
The mec-independent oxacillin non-susceptible S. aureus (MIONSA) strains represent a great clinical challenge, as they are not easily detected and can lead to treatment failure. However, the responsible molecular mechanisms are still very little understood. Here, we studied four clinical ST8-MSSA-t024 isolates recovered during the course of antibiotic treatment from a patient suffering successive episodes of bacteremia. The first isolates (SAMS1, SAMS2, and SAMS3) were susceptible to cefoxitin and oxacillin. The last one (SA2) was susceptible to cefoxitin, resistant to oxacillin, lacked mec genes, and had reduced susceptibility to teicoplanin. SA2 showed higher β-lactamase activity than SAMS1. However, β-lactamase hyperproduction could not be linked to oxacillin resistance as it was not inhibited by clavulanic acid, and no genetic changes that could account for its hyperproduction were found. Importantly, we hereby report the in vivo acquisition and coexistence of different adaptive mutations in genes associated with peptidoglycan synthesis (pbp2, rodA, stp1, yjbH, and yvqF/vraT), which is possibly related with the development of oxacillin resistance and reduced susceptibility to teicoplanin in SA2. Using three-dimensional models and PBP binding assays, we demonstrated the high contribution of the SA2 PBP2 Ala450Asp mutation to the observed oxacillin resistance phenotype. Our results should be considered as a warning for physicians and microbiologists in the region, as MIONSA detection and treatment represent an important clinical challenge. Full article
(This article belongs to the Special Issue ESKAPE Pathogen Infection and Antibiotic Resistance)
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16 pages, 2774 KiB  
Article
Optimizing Antibiotic Therapy for Stenotrophomonas maltophilia Infections in Critically Ill Patients: A Pharmacokinetic/Pharmacodynamic Approach
by Helena Barrasa, Miguel Angel Morán, Leire Fernández-Ciriza, Arantxa Isla, María Ángeles Solinís, Andrés Canut-Blasco and Alicia Rodríguez-Gascón
Antibiotics 2024, 13(6), 553; https://doi.org/10.3390/antibiotics13060553 - 13 Jun 2024
Viewed by 560
Abstract
Stenotrophomonas maltophilia is an opportunistic, multidrug-resistant non-fermentative Gram-negative bacillus, posing a significant challenge in clinical treatment due to its numerous intrinsic and acquired resistance mechanisms. This study aimed to evaluate the adequacy of antibiotics used for the treatment of S. maltophilia infections in [...] Read more.
Stenotrophomonas maltophilia is an opportunistic, multidrug-resistant non-fermentative Gram-negative bacillus, posing a significant challenge in clinical treatment due to its numerous intrinsic and acquired resistance mechanisms. This study aimed to evaluate the adequacy of antibiotics used for the treatment of S. maltophilia infections in critically ill patients using a pharmacokinetic/pharmacodynamic (PK/PD) approach. The antibiotics studied included cotrimoxazole, levofloxacin, minocycline, tigecycline, cefiderocol, and the new combination aztreonam/avibactam, which is not yet approved. By Monte Carlo simulations, the probability of target attainment (PTA), the PK/PD breakpoints, and the cumulative fraction of response (CFR) were estimated. PK parameters and MIC distributions were sourced from the literature, the European Committee on Antimicrobial Susceptibility Testing (EUCAST), and the SENTRY Antimicrobial Surveillance Program collection. Cefiderocol 2 g q8h, minocycline 200 mg q12h, tigecycline 100 mg q12h, and aztreonam/avibactam 1500/500 mg q6h were the best options to treat empirically infections due to S. maltophilia. Cotrimoxazole provided a higher probability of treatment success for the U.S. isolates than for European isolates. For all antibiotics, discrepancies between the PK/PD breakpoints and the clinical breakpoints defined by EUCAST (or the ECOFF) and CLSI were detected. Full article
(This article belongs to the Special Issue Antimicrobial Resistance and Therapy in Intensive Care Unit)
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9 pages, 488 KiB  
Article
Clinical Outcomes in Patients Who Received a One-Time Aminoglycoside Dose for Extended-Spectrum Beta-Lactamase-Producing Enterobacterales or Pseudomonas aeruginosa Cystitis
by Kelsey Bouwman and Melissa George
Antibiotics 2024, 13(6), 552; https://doi.org/10.3390/antibiotics13060552 - 13 Jun 2024
Viewed by 853
Abstract
The Infectious Diseases Society of America (IDSA) recommends a single dose of an aminoglycoside for uncomplicated cystitis caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales (ESBL-E) and difficult-to-treat Pseudomonas aeruginosa. However, there is very little recent clinical evidence to support this recommendation. The objective [...] Read more.
The Infectious Diseases Society of America (IDSA) recommends a single dose of an aminoglycoside for uncomplicated cystitis caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales (ESBL-E) and difficult-to-treat Pseudomonas aeruginosa. However, there is very little recent clinical evidence to support this recommendation. The objective of this study was to evaluate the safety and efficacy of a single-dose aminoglycoside for cystitis caused by ESBL-E or Pseudomonas aeruginosa. This was a multicenter, retrospective, cohort study. Patients who received ≥3 days of standard of care were compared to patients who received a one-time dose of an aminoglycoside with or without a short course of effective therapy before. The primary outcome was the rate of relapse defined as requiring escalation of antibiotics or starting new antibiotic therapy within 14 days after the completion of antibiotics. A total of 66 patients were included in this study, with 33 patients in each arm. There were more males and complicated cystitis patients in the standard-of-care group. There was no difference found in the rate of relapse. The length of stay was significantly shorter in the aminoglycoside group (4.5 ± 4.4 days vs. 14.1 ± 10.1 days, p < 0.0001). A one-time dose of an aminoglycoside did not increase the risk of relapse and was associated with a shorter length of stay when used to treat cystitis caused by ESBL-E or Pseudomonas aeruginosa. Full article
(This article belongs to the Special Issue Antimicrobial Resistance in Clinical Infection and Antibiotic Stewardship)
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17 pages, 932 KiB  
Review
Antimicrobial Resistance in Livestock: A Serious Threat to Public Health
by Roberto Bava, Fabio Castagna, Carmine Lupia, Giusi Poerio, Giovanna Liguori, Renato Lombardi, Maria Diana Naturale, Caterina Mercuri, Rosa Maria Bulotta, Domenico Britti and Ernesto Palma
Antibiotics 2024, 13(6), 551; https://doi.org/10.3390/antibiotics13060551 - 13 Jun 2024
Viewed by 1052
Abstract
Antimicrobial resistance represents an alarming public health problem; its importance is related to the significant clinical implications (increased morbidity, mortality, disease duration, development of comorbidities, and epidemics), as well as its economic effects on the healthcare sector. In fact, therapeutic options are severely [...] Read more.
Antimicrobial resistance represents an alarming public health problem; its importance is related to the significant clinical implications (increased morbidity, mortality, disease duration, development of comorbidities, and epidemics), as well as its economic effects on the healthcare sector. In fact, therapeutic options are severely limited by the advent and spread of germs resistant to many antibiotics. The situation worldwide is worrying, especially in light of the prevalence of Gram-negative bacteria—Klebsiella pneumoniae and Acinetobacter baumannii—which are frequently isolated in hospital environments and, more specifically, in intensive care units. The problem is compounded by the ineffective treatment of infections by patients who often self-prescribe therapy. Resistant bacteria also show resistance to the latest generation antibiotics, such as carbapenems. In fact, superbacteria, grouped under the acronym extended-spectrum betalactamase (ESBL), are becoming common. Antibiotic resistance is also found in the livestock sector, with serious repercussions on animal production. In general, this phenomenon affects all members of the biosphere and can only be addressed by adopting a holistic “One Health” approach. In this literature overview, a stock is taken of what has been learned about antibiotic resistance, and suggestions are proposed to stem its advance. Full article
(This article belongs to the Section Antibiotics in Animal Health)
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12 pages, 1643 KiB  
Article
Synergistic Combination of Aztreonam and Ceftazidime–Avibactam—A Promising Defense Strategy against OXA-48 + NDM Klebsiella pneumoniae in Romania
by Ioana Miriana Cismaru, Maria Cristina Văcăroiu, Elif Soium, Tiberiu Holban, Adelina Maria Radu, Violeta Melinte and Valeriu Gheorghiță
Antibiotics 2024, 13(6), 550; https://doi.org/10.3390/antibiotics13060550 - 12 Jun 2024
Viewed by 1057
Abstract
With the increasing burden of carbapenem-resistant Klebsiella pneumoniae (CR-Kp), including high rates of healthcare-associated infections, treatment failure, and mortality, a good therapeutic strategy for attacking this multi-resistant pathogen is one of the main goals in current medical practice and necessitates the use of [...] Read more.
With the increasing burden of carbapenem-resistant Klebsiella pneumoniae (CR-Kp), including high rates of healthcare-associated infections, treatment failure, and mortality, a good therapeutic strategy for attacking this multi-resistant pathogen is one of the main goals in current medical practice and necessitates the use of novel antibiotics or new drug combinations. Objectives: We reviewed the clinical and microbiological outcomes of seven patients treated at the “Agrippa Ionescu” Clinical Emergency Hospital between October 2023 and January 2024, aiming to demonstrate the synergistic activity of the ceftazidime–avibactam (C/A) plus aztreonam (ATM) combination against the co-producers of blaNDM + blaOXA-48-like CR-Kp. Material and Methods: Seven CR-Kp with blaNDM and blaOXA-48 as resistance mechanisms were tested. Seven patients treated with C/A + ATM were included. The synergistic activity of C/A + ATM was proven through double-disk diffusion in all seven isolates. Resistance mechanisms like KPC, VIM, OXA-48, NDM, IMP, and CTX-M were assessed through immunochromatography. Results: With a mean of nine days of treatment with the synergistic combination C/A + ATM, all patients achieved clinical recovery, and five achieved microbiological recovery. Conclusions: With the emerging co-occurrence of blaOXA-48 and blaNDM among Kp in Romania, the combination of C/A and ATM could be a promising therapeutic option. Full article
(This article belongs to the Special Issue Carbapenemases in Gram-Negative Bacteria: A Global Health Threat and Therapeutic Challenge)
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18 pages, 3856 KiB  
Article
Stability Studies of the Dilution Series of Different Antibiotic Stock Solutions in Culture Medium Incubated at 37 °C
by Ádám Kerek, Bence G. Ecsedi, Ábel Szabó, Zoltán Szimrók, Bianka Paliczné Kustán, Ákos Jerzsele and Gábor Nagy
Antibiotics 2024, 13(6), 549; https://doi.org/10.3390/antibiotics13060549 - 12 Jun 2024
Viewed by 504
Abstract
The long-term stability of antibiotics in culture media remains underexplored in scientific literature. This study evaluated the stability of eight distinct antibiotic stock solutions—amoxicillin, cefotaxime, neomycin, oxytetracycline, florfenicol, enrofloxacin, colistin, and potentiated sulfonamide—and their 10-fold dilution series in tryptone soy broth (TSB) at [...] Read more.
The long-term stability of antibiotics in culture media remains underexplored in scientific literature. This study evaluated the stability of eight distinct antibiotic stock solutions—amoxicillin, cefotaxime, neomycin, oxytetracycline, florfenicol, enrofloxacin, colistin, and potentiated sulfonamide—and their 10-fold dilution series in tryptone soy broth (TSB) at 37 °C, over 12 days. Samples were collected immediately after preparation and on days 1, 2, 5, 7, 9, and 12, with active substance concentrations measured using ultra-high-performance liquid chromatography (UHPLC) coupled with mass spectrometry. The results indicated that among the ultrapure water stock solutions, neomycin, florfenicol, and potentiated sulfonamide maintained stability (>95%). Within the culture medium, florfenicol showed consistent stability (100%) throughout the study, potentiated sulfonamide experienced minor degradation (>85%), and neomycin underwent significant degradation. Amoxicillin, oxytetracycline, and colistin displayed considerable degradation in both solution types but were more stable in ultrapure water solutions. The stability of cefotaxime and enrofloxacin in ultrapure water solutions and in the medium was very similar when compared; however, 3.6% of the former and 88.7% of the latter remained detectable by day 12. These findings are crucial for minimum inhibitory concentration (MIC) assessments, especially in minimum bactericidal concentration (MBC) studies, and in experiments concerning long-term evolution and co-selection. This study underscores the necessity of stability assessments in culture media to validate future experimental outcomes. Full article
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12 pages, 661 KiB  
Article
Exploring Prescription Practices: Insights from an Antimicrobial Stewardship Program at a Tertiary Healthcare Facility, Rwanda
by Misbah Gashegu, Noel Gahamanyi, François Xavier Ndayambaje, Jean Bosco Munyemana, Vedaste Ndahindwa, Fredrick Lukwago, Lambert Ingabire, Fiona Gambanga, Pierre Gashema, Albert Tuyishime, Tafadzwa Dzinamarira, Damas Dukundane, Thierry Zawadi Muvunyi and Claude Mambo Muvunyi
Antibiotics 2024, 13(6), 548; https://doi.org/10.3390/antibiotics13060548 - 12 Jun 2024
Viewed by 899
Abstract
Antimicrobial resistance (AMR) is a major public health threat linked to increased morbidity and mortality. It has the potential to return us to the pre-antibiotic era. Antimicrobial stewardship (AMS) programs are recognized as a key intervention to improve antimicrobial use and combat AMR. [...] Read more.
Antimicrobial resistance (AMR) is a major public health threat linked to increased morbidity and mortality. It has the potential to return us to the pre-antibiotic era. Antimicrobial stewardship (AMS) programs are recognized as a key intervention to improve antimicrobial use and combat AMR. However, implementation of AMS remains limited in Africa, particularly in Rwanda. This study aimed to assess prescription practices, identify areas for improvement, and promote adherence to AMS principles. Conducted at King Faisal Hospital in Rwanda, this qualitative study used semi-structured interviews with eight participants until saturation was reached. The interviews were recorded, transcribed, and thematically analyzed, revealing four emerging themes. The first theme was on AMS activities that were working well based on availability of microbiology laboratory results and prescription guidelines as factors influencing antibiotic prescription adjustments. The second theme was related to challenges during the implementation of the AMS program, including the prescription of broad-spectrum antibiotics, limited local data on AMR patterns, and stock-outs of essential antibiotics. The third theme was on the importance of adhering to AMR management guidelines at KFH. The last emerged on recommendations from participants centered on regular training for healthcare workers, widespread dissemination of AMR findings across departments, and the enforcement of antibiotic restriction policies. These actions can improve prescription behaviors, upholding the highest standards of patient care, and strengthening the nascent AMS program. Full article
(This article belongs to the Special Issue Surveillance and Optimization of Antibiotics Usage)
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12 pages, 248 KiB  
Article
Urinary Tract Infections among Febrile Infants in Qatar: Extended-Spectrum-Beta-Lactamase (ESBL)-Producing Versus Non-ESBL Organisms
by Mohammad Qusad, Ihsan Elhalabi, Samer Ali, Khaled Siddiq, Lujain Loay, Abdallah Aloteiby, Ghada Al Ansari, Bassem Moustafa, Tawa Olukade, Mohammed Al Amri, Ashraf Soliman and Ahmed Khalil
Antibiotics 2024, 13(6), 547; https://doi.org/10.3390/antibiotics13060547 - 12 Jun 2024
Viewed by 568
Abstract
Background: The escalating prevalence of ESBL-producing Enterobacteriaceae in Qatar’s pediatric population, especially in community-onset febrile urinary tract infections (FUTIs), necessitates a comprehensive investigation into this concerning trend. Results: Over the course of one year, a total of 459 infants were diagnosed and subsequently [...] Read more.
Background: The escalating prevalence of ESBL-producing Enterobacteriaceae in Qatar’s pediatric population, especially in community-onset febrile urinary tract infections (FUTIs), necessitates a comprehensive investigation into this concerning trend. Results: Over the course of one year, a total of 459 infants were diagnosed and subsequently treated for UTIs. Cases primarily occurred in infants aged over 60 days, predominantly non-Qatari females born from term pregnancies. Notably, E. coli and K. pneumoniae were the most frequently identified organisms, accounting for 79.7% and 9.8% in the ESBL group and 57.2% and 18.7% in the non-ESBL group, respectively. Interestingly, hydronephrosis emerged as the most prevalent urological anomaly detected in both ESBL (n = 10) and other organism (n = 19) groups. Methods: In this retrospective cohort study conducted in Qatar, we meticulously evaluated the prevalence of pediatric FUTIs. Our study focused on febrile infants aged less than 1 year, excluding those with urine samples not obtained through a catheter. Conclusions: E. coli and K. pneumoniae prevailed as the predominant causative agents in febrile children in Qatar, with hydronephrosis being identified as the most common urological anomaly. Moreover, our findings suggested that gentamicin served as a viable non-carbapenem option for hospitalized ESBL cases, while oral nitrofurantoin showed considerable promise for uncomplicated ESBL UTIs. Full article
13 pages, 363 KiB  
Article
Accordance of Registered Drug Packages with Guideline-Recommended Treatment Durations for Community-Acquired Pneumonia—A New Antibiotic Stewardship Target?
by Martina Prusac, Maja Ortner Hadziabdic, Doris Rusic and Darko Modun
Antibiotics 2024, 13(6), 546; https://doi.org/10.3390/antibiotics13060546 - 12 Jun 2024
Viewed by 598
Abstract
In most countries, antibiotics for oral administration are put on the market in fixed packages. When there is no exact unit dispensing of antimicrobials, drug pack size may influence prescribers’ choice of treatment duration. The aim of this study was to investigate the [...] Read more.
In most countries, antibiotics for oral administration are put on the market in fixed packages. When there is no exact unit dispensing of antimicrobials, drug pack size may influence prescribers’ choice of treatment duration. The aim of this study was to investigate the accordance of approved antibiotic packages with national guidelines for the treatment of community-acquired pneumonia (CAP). For the purpose of this study, criteria were developed to determine the accordance of approved antibiotic packages for treating CAP (criteria), which are based on recommendations from national guidelines for treating CAP. Subsequently, the accordance of approved antibiotic packages with the number of antibiotic doses resulting from the specified criteria was determined. Of 39 identified therapeutic option-package size combinations, 11 were found to be matched (28.2%), meaning there were no leftover medication units after completing therapy, and 28 were mismatched combinations (71.8%), indicating that there were excess doses of antibiotics remaining at the end of therapy. The results of this research showed a significant non-accordance of the approved antibiotic packages with the national guidelines for the treatment of CAP and, consequently, the creation of a large amount of residues of unit doses of antibiotics in the community. Full article
(This article belongs to the Special Issue Antimicrobial Prescribing and Antimicrobial Use in Healthcare Settings)
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12 pages, 586 KiB  
Systematic Review
The Evolving Challenge of Appropriate Antibiotics Use in Hospitalized COVID-19 Patients: A Systematic Literature Review
by Guido Granata and Stefania Cicalini
Antibiotics 2024, 13(6), 545; https://doi.org/10.3390/antibiotics13060545 - 12 Jun 2024
Viewed by 591
Abstract
The issue of bacterial infections in COVID-19 patients has received increasing attention. Scant data are available on the impact of bacterial superinfection and antibiotic administration on the outcome of hospitalized COVID-19 patients. We conducted a literature review from 1 January 2022 to 31 [...] Read more.
The issue of bacterial infections in COVID-19 patients has received increasing attention. Scant data are available on the impact of bacterial superinfection and antibiotic administration on the outcome of hospitalized COVID-19 patients. We conducted a literature review from 1 January 2022 to 31 March 2024 to assess the current burden of bacterial infection and the evidence for antibiotic use in hospitalized COVID-19 patients. Published articles providing data on antibiotic use in COVID-19 patients were identified through computerized literature searches with the search terms [(antibiotic) AND (COVID-19)] or [(antibiotic treatment) AND (COVID-19)]. PubMed and SCOPUS databases were searched from 1 January 2022 to 31 March 2024. No attempt was made to obtain information about unpublished studies. English language restriction was applied. The quality of the included studies was evaluated by the tool recommended by the Joanna Briggs Institute. Both quantitative and qualitative information were summarized by means of textual descriptions. Five hundred fifty-one studies were identified, and twenty-nine studies were included in this systematic review. Of the 29 included studies, 18 studies were on the prevalence of bacterial infection and antibiotic use in hospitalized COVID-19 patients; 4 studies reported on the efficacy of early antibiotic use in COVID-19; 4 studies were on the use of sepsis biomarkers to improve antibiotic use; 3 studies were on the efficacy of antimicrobial stewardship programs and predictive models among COVID-19-hospitalized patients. The quality of included studies was high in 35% and medium in 62%. High rates of hospital-acquired infections were reported among COVID-19 patients, ranging between 7.5 and 37.7%. A high antibiotic resistance rate was reported among COVID-19 patients developing hospital-acquired infections, with a high in-hospital mortality rate. The studies evaluating multi-faceted antimicrobial stewardship interventions reported efficacy in decreasing antibiotic consumption and lower in-hospital mortality. Full article
(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)
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15 pages, 2051 KiB  
Article
Anti-Infective Activity of Momordica charantia Extract with Molecular Docking of Its Triterpenoid Glycosides
by Mohammed Aldholmi, Rizwan Ahmad, Mohammad Habeeb Shaikh, Ayad Mohammed Salem, Maher Alqurashi and Mansour Alturki
Antibiotics 2024, 13(6), 544; https://doi.org/10.3390/antibiotics13060544 - 11 Jun 2024
Viewed by 529
Abstract
Momordica charantia, commonly known as bitter melon, is a fruiting plant that has been used for several diseases including infectious diseases. In this study, we report the antibacterial, antifungal, and antiviral activity of different bitter melon fruit parts originating from India and [...] Read more.
Momordica charantia, commonly known as bitter melon, is a fruiting plant that has been used for several diseases including infectious diseases. In this study, we report the antibacterial, antifungal, and antiviral activity of different bitter melon fruit parts originating from India and Saudi Arabia. The in vitro experiments are supported by the molecular docking of karavilosides to verify their role in the bioactivity. The antimicrobial assays revealed activity against Candida albicans, Escherichia coli, and Staphylococcus aureus. The extracts exhibited the potent inhibition of HIV-I reverse transcriptase, with an IC50 of 0.125 mg/mL observed for the pith extract originating from Saudi Arabia and the standard drug doxorubicin. The molecular docking of karavilosides exhibited a significant affinity to reverse transcriptase comparable to Rilpivirine and higher than that of doxorubicin. These outcomes encourage the precious bioactive components of the seed and pith of the Saudi bitter melon fruits to be further studied for isolation and structure elucidation. Full article
(This article belongs to the Special Issue Plants, Lichens, Fungi, and Algae Extracts and Derivatives with Antimicrobial Properties for Nutrition and Health)
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22 pages, 951 KiB  
Article
Whole-Genome Sequencing of Human and Porcine Escherichia coli Isolates on a Commercial Pig Farm in South Africa
by Wilhelmina Strasheim, Michelle Lowe, Anthony M. Smith, Eric M. C. Etter and Olga Perovic
Antibiotics 2024, 13(6), 543; https://doi.org/10.3390/antibiotics13060543 - 11 Jun 2024
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Abstract
Escherichia coli is an indicator micro-organism in One Health antibiotic resistance surveillance programs. The purpose of the study was to describe and compare E. coli isolates obtained from pigs and human contacts from a commercial farm in South Africa using conventional methods and whole-genome [...] Read more.
Escherichia coli is an indicator micro-organism in One Health antibiotic resistance surveillance programs. The purpose of the study was to describe and compare E. coli isolates obtained from pigs and human contacts from a commercial farm in South Africa using conventional methods and whole-genome sequencing (WGS). Porcine E. coli isolates were proportionally more resistant phenotypically and harbored a richer diversity of antibiotic resistance genes as compared to human E. coli isolates. Different pathovars, namely ExPEC (12.43%, 21/169), ETEC (4.14%, 7/169), EPEC (2.96%, 5/169), EAEC (2.96%, 5/169) and STEC (1.18%, 2/169), were detected at low frequencies. Sequence type complex (STc) 10 was the most prevalent (85.51%, 59/169) among human and porcine isolates. Six STcs (STc10, STc86, STc168, STc206, STc278 and STc469) were shared at the human–livestock interface according to multilocus sequence typing (MLST). Core-genome MLST and hierarchical clustering (HC) showed that human and porcine isolates were overall genetically diverse, but some clustering at HC2–HC200 was observed. In conclusion, even though the isolates shared a spatiotemporal relationship, there were still differences in the virulence potential, antibiotic resistance profiles and cgMLST and HC according to the source of isolation. Full article
(This article belongs to the Special Issue Antimicrobial Resistance in Animals and Animal Products and Its Environmental Transmission Aspects)
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12 pages, 1553 KiB  
Article
Demographic Characteristics and Economic Burden of Clostridioides difficile Infection in Korea: A Nationwide Population-Based Study after Propensity Score Matching
by Jae Myung Cha, Jin Young Yoon, Min Seob Kwak, Moonhyung Lee and Young-Seok Cho
Antibiotics 2024, 13(6), 542; https://doi.org/10.3390/antibiotics13060542 - 10 Jun 2024
Viewed by 509
Abstract
Clostridioides difficile infection (CDI) poses a considerable threat to global public health. However, there have been insufficient propensity score-matched data on its demographic characteristics and economic burden. Using nationwide claims data, we assessed longitudinal changes in the demographic characteristics and economic burden of [...] Read more.
Clostridioides difficile infection (CDI) poses a considerable threat to global public health. However, there have been insufficient propensity score-matched data on its demographic characteristics and economic burden. Using nationwide claims data, we assessed longitudinal changes in the demographic characteristics and economic burden of CDI between 2011 and 2019 after propensity score matching. We performed a regression analysis to compare the differences in the length of hospital stay and medical costs between patients with CDI and controls (gastroenteritis and colitis). The CDI hospitalization rate increased 2.9-fold between 2011 and 2019. The CDI group had higher comorbidity index scores and was more frequently diagnosed at tertiary hospitals and in the Seoul region than the control group (all p < 0.001). The annual incidence rate of CDI/10,000 persons significantly increased in both sexes and all age groups. The length of hospital stay and medical costs were 3.3-fold and 5.0-fold greater, respectively, in the CDI than in the control group (both p < 0.001). Although the length of hospital stay decreased, total medical costs increased in all age groups and both sexes between 2011 and 2019 (all p < 0.001). When compared with the control group, the CDI-attributable length of hospital stay and medical cost were greater by 15.3 days and KRW 3413 (×103), respectively, after matching. In conclusion, CDI incidence, particularly among the elderly population with comorbidities, has been increasing. In addition, the length of hospital stay and total medical costs of the CDI group were greater than those of the control group. Full article
(This article belongs to the Special Issue Clostridioides difficile Infection, 3rd Edition)
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