Hospital Acquired Infections, Multidrug Resistant (MDR) Bacteria, Alternative Approaches to Antibiotic Therapy

A special issue of Antibiotics (ISSN 2079-6382).

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 27186

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Dear Colleagues,

Resistance to known and currently used antibiotics represents a growing issue worldwide. It poses a major problem in the treatment of infectious diseases in general and hospital-acquired infections in particular. This is in part due to the overuse and misuse of antibiotics in past decades, which led to the selection of highly resistant bacteria and even so-called superbugs – multidrug-resistant (MDR) bacteria. Nosocomial infections, particularly, are often caused by MDR bacterial pathogens and the treatment of such infections is very complicated and extensive, often leading to various side effects. Even though MDR bacteria are widespread globally, their epidemiology varies by region. Hospital-acquired infections caused by MDR bacteria remain an unresolved problem in the healthcare system. A very important part of the overall therapeutic approach is the microbiological examination of adequate clinical materials, in particular blood culture tests. The obtained results allow targeted antibiotic therapy based on the identification of bacterial pathogens and the determination of their susceptibility/resistance to antibiotics. Molecular genetic methods are an integral part of solving the problem of bacterial resistance. Only adequately selected molecular typing methods may confirm or rule out epidemiologically related cases. If a new outbreak or merely increased rate of MDR bacteria is reasonably suspected, the clonal relationship of strains needs to be analyzed to reveal the source or route of transmission.

At the same time, the development of novel antibiotics is lagging with very few new ones in the pipeline. Finding viable alternatives to treat such infections may help to overcome these therapeutic issues.

This Special Issue will publish papers exploring developments in the field of bacterial resistance, mainly in the hospital settings, adequate antibiotic therapy, and identification of compounds useful to battle this growing issue.

Prof. Dr. Pavel Bostik
Prof. Dr. Milan Kolar
Guest Editors

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Keywords

  • Multidrug resistant bacteria
  • Molecular typing
  • Hospital acquired infections
  • Antibiotic therapy
  • Antibiotic compounds

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Published Papers (10 papers)

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Research

13 pages, 1374 KiB  
Article
Clinical Implication of the Relationship between Antimicrobial Resistance and Infection Control Activities in Japanese Hospitals: A Principal Component Analysis-Based Cluster Analysis
by Tomokazu Shoji, Natsu Sato, Haruhisa Fukuda, Yuichi Muraki, Keishi Kawata and Manabu Akazawa
Antibiotics 2022, 11(2), 229; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics11020229 - 10 Feb 2022
Cited by 3 | Viewed by 2207
Abstract
There are few multicenter investigations regarding the relationship between antimicrobial resistance (AMR) and infection-control activities in Japanese hospitals. Hence, we aimed to identify Japanese hospital subgroups based on facility characteristics and infection-control activities. Moreover, we evaluated the relationship between AMR and hospital subgroups. [...] Read more.
There are few multicenter investigations regarding the relationship between antimicrobial resistance (AMR) and infection-control activities in Japanese hospitals. Hence, we aimed to identify Japanese hospital subgroups based on facility characteristics and infection-control activities. Moreover, we evaluated the relationship between AMR and hospital subgroups. We conducted a cross-sectional study using administrative claims data and antimicrobial susceptibility data in 124 hospitals from April 2016 to March 2017. Hospitals were classified using cluster analysis based the principal component analysis-transformed data. We assessed the relationship between each cluster and AMR using analysis of variance. Ten variables were selected and transformed into four principal components, and five clusters were identified. Cluster 5 had high infection control activity. Cluster 2 had partially lower activity of infection control than the other clusters. Clusters 3 and 4 had a higher rate of surgeries than Cluster 1. The methicillin-resistant Staphylococcus aureus (MRSA)/S. aureus detection rate was lowest in Cluster 1, followed, respectively, by Clusters 5, 2, 4, and 3. The MRSA/S. aureus detection rate differed significantly between Clusters 4 and 5 (p = 0.0046). Our findings suggest that aggressive examination practices are associated with low AMR whereas surgeries, an infection risk factor, are associated with high AMR. Full article
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13 pages, 810 KiB  
Article
Molecular and Anti-Microbial Resistance (AMR) Profiling of Methicillin-Resistant Staphylococcus aureus (MRSA) from Hospital and Long-Term Care Facilities (LTCF) Environment
by Bing-Mu Hsu, Jung-Sheng Chen, I-Ching Lin, Gwo-Jong Hsu, Suprokash Koner, Bashir Hussain, Shih-Wei Huang and Hsin-Chi Tsai
Antibiotics 2021, 10(6), 748; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10060748 - 21 Jun 2021
Cited by 9 | Viewed by 2840
Abstract
To provide evidence of the cross-contamination of emerging pathogenic microbes in a local network between long-term care facilities (LTCFs) and hospitals, this study emphasizes the molecular typing, the prevalence of virulence genes, and the antibiotic resistance pattern of methicillin-resistant Staphylococcus aureus. MRSA [...] Read more.
To provide evidence of the cross-contamination of emerging pathogenic microbes in a local network between long-term care facilities (LTCFs) and hospitals, this study emphasizes the molecular typing, the prevalence of virulence genes, and the antibiotic resistance pattern of methicillin-resistant Staphylococcus aureus. MRSA isolates were characterized from 246 samples collected from LTCFs, medical tubes of LTCF residents, and hospital environments of two cities, Chiayi and Changhua. Species identification, molecular characterization, and drug resistance analysis were performed. Hospital environments had a higher MRSA detection rate than that of LTCF environments, where moist samples are a hotspot of MRSA habitats, including tube samples from LTCF residents. All MRSA isolates in this study carried the exfoliative toxin eta gene (100%). The majority of MRSA isolates were resistant to erythromycin (76.7%), gentamicin (60%), and ciprofloxacin (55%). The percentage of multidrug-resistant MRSA isolates was approximately 50%. The enterobacterial repetitive intergenic consensus polymerase chain reaction results showed that 18 MRSA isolates belonged to a specific cluster. This implied that genetically similar isolates were spread between hospitals and LTCFs in Changhua city. This study highlights the threat to the health of LTCFs’ residents posed by hospital contact with MRSA. Full article
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10 pages, 238 KiB  
Article
Clinical and Economic Impact of Community-Onset Urinary Tract Infections Caused by ESBL-Producing Klebsiella pneumoniae Requiring Hospitalization in Spain: An Observational Cohort Study
by Dawid Rozenkiewicz, Erika Esteve-Palau, Mar Arenas-Miras, Santiago Grau, Xavier Duran, Luisa Sorlí, María Milagro Montero and Juan P. Horcajada
Antibiotics 2021, 10(5), 585; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10050585 - 15 May 2021
Cited by 6 | Viewed by 2339
Abstract
Objective: To analyze the clinical and economic impact of community-onset urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae requiring hospitalization. Methods: A retrospective cohort study that included all adults with a UTI caused by K. pneumoniae that were [...] Read more.
Objective: To analyze the clinical and economic impact of community-onset urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae requiring hospitalization. Methods: A retrospective cohort study that included all adults with a UTI caused by K. pneumoniae that were admitted to a tertiary care hospital in Barcelona, Spain, between 2011 and 2015. Demographic, clinical, and economic data were analyzed. Results: One hundred and seventy-three episodes of UTIs caused by K. pneumoniae were studied; 112 were non-ESBL-producing and 61 were ESBL-producing. Multivariate analysis identified ESBL production, acute confusional state associated with UTI, shock, and the time taken to obtain adequate treatment as risk factors for clinical failure during the first seven days. An economic analysis showed differences between ESBL-producing and non-ESBL-producing K. pneumoniae for the total cost of hospitalization per episode (mean EUR 6718 vs EUR 3688, respectively). Multivariate analysis of the higher costs of UTI episodes found statistically significant differences for ESBL production and the time taken to obtain adequate treatment. Conclusion: UTIs caused by ESBL-producing K. pneumoniae requiring hospitalization and the time taken to obtain adequate antimicrobial therapy are associated with worse clinical and economic outcomes. Full article
13 pages, 1998 KiB  
Article
Heterogeneity of Antibiotics Multidrug-Resistance Profile of Uropathogens in Romanian Population
by Răzvan-Cosmin Petca, Silvius Negoiță, Cristian Mareș, Aida Petca, Răzvan-Ionuț Popescu and Călin Bogdan Chibelean
Antibiotics 2021, 10(5), 523; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10050523 - 02 May 2021
Cited by 22 | Viewed by 1938
Abstract
Urinary tract infections (UTIs) are a leading cause of morbidity for both males and females. The overconsumption of antibiotics in general medicine, veterinary, or agriculture has led to a spike in drug-resistant microorganisms; obtaining standardized results is imposed by standard definitions for various [...] Read more.
Urinary tract infections (UTIs) are a leading cause of morbidity for both males and females. The overconsumption of antibiotics in general medicine, veterinary, or agriculture has led to a spike in drug-resistant microorganisms; obtaining standardized results is imposed by standard definitions for various categories of drug-resistant bacteria—such as multiple-drug resistant (MDR), extensive drug-resistant (XDR), and pan drug-resistant (PDR). This retrospective study conducted in three university teaching hospitals in Romania has analyzed urine probes from 15,231 patients, of which 698 (4.58%) presented multidrug-resistant strains. Escherichia coli was the leading uropathogen 283 (40.54%), presenting the highest resistance to quinolones (R = 72.08%) and penicillin (R = 66.78%) with the most important patterns of resistance for penicillin, sulfonamides, and quinolones (12.01%) and aminoglycosides, aztreonam, cephalosporins, and quinolones (9.89%). Klebsiella spp. followed—260 (37.24%) with the highest resistance to amoxicillin-clavulanate (R = 94.61%) and cephalosporins (R = 94.23%); the leading patterns were observed for aminoglycosides, aminopenicillins + β-lactams inhibitor, sulfonamides, and cephalosporins (12.69%) and aminoglycosides, aztreonam, cephalosporins, quinolones (9.23%). The insufficient research of MDR strains on the Romanian population is promoting these findings as an important tool for any clinician treating MDR-UTIs. Full article
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12 pages, 596 KiB  
Article
Short-Course Versus Long-Course Colistin for Treatment of Carbapenem-Resistant A.baumannii in Cancer Patient
by Wasan Katip, Suriyon Uitrakul and Peninnah Oberdorfer
Antibiotics 2021, 10(5), 484; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10050484 - 22 Apr 2021
Cited by 8 | Viewed by 1996
Abstract
Carbapenem-resistant Acinetobacter baumannii (CRAB) is one of the most commonly reported nosocomial infections in cancer patients and could be fatal because of suboptimal immune defenses in these patients. We aimed to compare clinical response, microbiological response, nephrotoxicity, and 30-day mortality between cancer patients [...] Read more.
Carbapenem-resistant Acinetobacter baumannii (CRAB) is one of the most commonly reported nosocomial infections in cancer patients and could be fatal because of suboptimal immune defenses in these patients. We aimed to compare clinical response, microbiological response, nephrotoxicity, and 30-day mortality between cancer patients who received short (<14 days) and long (≥14 days) courses of colistin for treatment of CRAB infection. A retrospective cohort study was conducted in cancer patients with CRAB infection who received short or long courses of colistin between 2015 to 2017 at Chiang Mai University Hospital (CMUH). A total of 128 patients met the inclusion criteria. The results of this study show that patients who received long course of colistin therapy had a higher rate of clinical response; adjusted odds ratio (OR) was 3.16 times in patients receiving long-course colistin therapy (95%CI, 1.37–7.28; p value = 0.007). Microbiological response in patients with long course was 4.65 times (adjusted OR) higher than short course therapy (95%CI, 1.72–12.54; p value = 0.002). Moreover, there was no significant difference in nephrotoxicity (adjusted OR, 0.91, 95%CI, 0.39–2.11; p value = 0.826) between the two durations of therapy. Thirty-day mortality in the long-course therapy group was 0.11 times (adjusted OR) compared to the short-course therapy group (95%CI, 0.03–0.38; p value = 0.001). Propensity score analyses also demonstrated similar results. In conclusion, cancer patients who received a long course of colistin therapy presented greater clinical and microbiological responses and lower 30-day mortality but similar nephrotoxicity as compared with those who a received short course. Therefore, a long course of colistin therapy should be considered for management of CRAB infection in cancer patients. Full article
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16 pages, 1422 KiB  
Article
Antibiotic Resistance, spa Typing and Clonal Analysis of Methicillin-Resistant Staphylococcus aureus (MRSA) Isolates from Blood of Patients Hospitalized in the Czech Republic
by Katarina Pomorska, Vladislav Jakubu, Lucia Malisova, Marta Fridrichova, Martin Musilek and Helena Zemlickova
Antibiotics 2021, 10(4), 395; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10040395 - 06 Apr 2021
Cited by 14 | Viewed by 2825
Abstract
Staphylococcus aureus is one of the major causes of bloodstream infections. The aim of our study was to characterize methicillin-resistant Staphylococcus aureus (MRSA) isolates from blood of patients hospitalized in the Czech Republic between 2016 and 2018. All MRSA strains were tested for [...] Read more.
Staphylococcus aureus is one of the major causes of bloodstream infections. The aim of our study was to characterize methicillin-resistant Staphylococcus aureus (MRSA) isolates from blood of patients hospitalized in the Czech Republic between 2016 and 2018. All MRSA strains were tested for antibiotic susceptibility, analyzed by spa typing and clustered using a Based Upon Repeat Pattern (BURP) algorithm. The representative isolates of the four most common spa types and representative isolates of all spa clonal complexes were further typed by multilocus sequence typing (MLST) and staphylococcal cassette chromosome mec (SCCmec) typing. The majority of MRSA strains were resistant to ciprofloxacin (94%), erythromycin (95.5%) and clindamycin (95.6%). Among the 618 strains analyzed, 52 different spa types were detected. BURP analysis divided them into six different clusters. The most common spa types were t003, t586, t014 and t002, all belonging to the CC5 (clonal complex). CC5 was the most abundant MLST CC of our study, comprising of 91.7% (n = 565) of spa-typeable isolates. Other CCs present in our study were CC398, CC22, CC8, CC45 and CC97. To our knowledge, this is the biggest nationwide study aimed at typing MRSA blood isolates from the Czech Republic. Full article
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11 pages, 1032 KiB  
Article
Effect of N-Acetylcysteine Administration on 30-Day Mortality in Critically Ill Patients with Septic Shock Caused by Carbapenem-Resistant Klebsiella pneumoniae and Acinetobacter baumannii: A Retrospective Case-Control Study
by Alessandra Oliva, Alessandro Bianchi, Alessandro Russo, Giancarlo Ceccarelli, Francesca Cancelli, Fulvio Aloj, Danilo Alunni Fegatelli, Claudio Maria Mastroianni and Mario Venditti
Antibiotics 2021, 10(3), 271; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10030271 - 08 Mar 2021
Cited by 15 | Viewed by 2593
Abstract
Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) and Acinetobacter baumannii (CR-Ab) represent important cause of severe infections in intensive care unit (ICU) patients. N-Acetylcysteine (NAC) is a mucolytic agent with antioxidant and anti-inflammatory properties, showing also in-vitro antibacterial activity. Aim was to evaluate the effect [...] Read more.
Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) and Acinetobacter baumannii (CR-Ab) represent important cause of severe infections in intensive care unit (ICU) patients. N-Acetylcysteine (NAC) is a mucolytic agent with antioxidant and anti-inflammatory properties, showing also in-vitro antibacterial activity. Aim was to evaluate the effect on 30-day mortality of the addition of intravenous NAC to antibiotics in ICU patients with CR-Kp or CR-Ab septic shock. A retrospective, observational case:control study (1:2) in patients with septic shock caused by CR-Kp or CR-Ab hospitalized in two different ICUs was conducted. Cases included patients receiving NAC plus antimicrobials, controls included patients not receiving NAC. Cases and controls were matched for age, SAPS II, causative agent and source of infection. No differences in age, sex, SAPS II score or time to initiate definitive therapy were observed between cases and controls. Pneumonia and bacteremia were the leading infections. Overall, mortality was 48.9% (33.3% vs. 56.7% in cases and controls, p = 0.05). Independent risk factors for mortality were not receiving NAC (p = 0.002) and CR-Ab (p = 0.034) whereas therapy with two in-vitro active antibiotics (p = 0.014) and time to initial definite therapy (p = 0.026) were protective. NAC plus antibiotics might reduce the 30-day mortality rate in ICU patients with CR-Kp and CR-Ab septic shock. Full article
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8 pages, 272 KiB  
Article
Spread of Linezolid-Resistant Enterococcus spp. in Human Clinical Isolates in the Czech Republic
by Lucia Mališová, Vladislav Jakubů, Katarína Pomorská, Martin Musílek and Helena Žemličková
Antibiotics 2021, 10(2), 219; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10020219 - 22 Feb 2021
Cited by 14 | Viewed by 2569
Abstract
The aim of this study was to map and investigate linezolid resistance mechanisms in linezolid-resistant enterococci in the Czech Republic from 2009 to 2019. Altogether, 1442 isolates of Enterococcus faecium and Enterococcus faecalis were examined in the National Reference Laboratory for Antibiotics. Among [...] Read more.
The aim of this study was to map and investigate linezolid resistance mechanisms in linezolid-resistant enterococci in the Czech Republic from 2009 to 2019. Altogether, 1442 isolates of Enterococcus faecium and Enterococcus faecalis were examined in the National Reference Laboratory for Antibiotics. Among them, 8% of isolates (n = 115) were resistant to linezolid (E. faecium/n = 106, E. faecalis/n = 9). Only three strains of E. faecium were resistant to tigecycline, 72.6% of isolates were resistant to vancomycin. One isolate of E. faecium harbored the cfr gene. The majority (87%, n = 11) of E. faecium strains were resistant to linezolid because of the mutation G2576T in the domain V of the 23S rRNA. This mutation was detected also in two strains of E. faecalis. The presence of the optrA gene was the dominant mechanism of linezolid resistance in E. faecalis isolates. None of enterococci contained cfrB, poxtA genes, or any amino acid mutation in genes encoding ribosomal proteins. No mechanism of resistance was identified in 4 out of 106 E. faecium linezolid resistant isolates in this study. Seventeen sequence types (STs) including four novel STs were identified in this work. Clonal complex CC17 was found in all E. faecium isolates. Full article
16 pages, 1087 KiB  
Article
Implementation of Antibiotic Stewardship in a University Hospital Setting
by Milan Kolar, Miroslava Htoutou Sedlakova, Karel Urbanek, Patrik Mlynarcik, Magdalena Roderova, Kristyna Hricova, Kristyna Mezerova, Pavla Kucova, Jana Zapletalova, Katerina Fiserova and Pavel Kurfurst
Antibiotics 2021, 10(1), 93; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10010093 - 19 Jan 2021
Cited by 11 | Viewed by 3188
Abstract
The article describes activities of an antibiotic center at a university hospital in the Czech Republic and presents the results of antibiotic stewardship program implementation over a period of 10 years. It provides data on the development of resistance of Escherichia coli, [...] Read more.
The article describes activities of an antibiotic center at a university hospital in the Czech Republic and presents the results of antibiotic stewardship program implementation over a period of 10 years. It provides data on the development of resistance of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Staphylococcus aureus to selected antibiotic agents as well as consumption data for various antibiotic classes. The genetic basis of resistance to beta-lactam antibiotics and its clonal spread were also assessed. The study showed significant correlations between aminoglycoside consumption and resistance of Escherichia coli and Klebsiella pneumoniae to gentamicin (r = 0.712, r = 0.869), fluoroquinolone consumption and resistance of Klebsiella pneumoniae to ciprofloxacin (r = 0.896), aminoglycoside consumption and resistance of Pseudomonas aeruginosa to amikacin (r = 0.716), as well as carbapenem consumption and resistance of Pseudomonas aeruginosa to meropenem (r = 0.855). Genotyping of ESBL- positive isolates of Klebsiella pneumoniae and Escherichia coli showed a predominance of CTX-M-type; in AmpC-positive strains, DHA, EBC and CIT enzymes prevailed. Of 19 meropenem-resistant strains of Klebsiella pneumoniae, two were identified as NDM-positive. Clonal spread of these strains was not detected. The results suggest that comprehensive antibiotic stewardship implementation in a healthcare facility may help to maintain the effectiveness of antibiotics against bacterial pathogens. Particularly beneficial is the work of clinical microbiologists who, among other things, approve administration of antibiotics to patients with bacterial infections and directly participate in their antibiotic therapy. Full article
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10 pages, 602 KiB  
Article
Analysis of Vancomycin-Resistant Enterococci in Hemato-Oncological Patients
by Kristýna Hricová, Taťána Štosová, Pavla Kučová, Kateřina Fišerová, Jan Bardoň and Milan Kolář
Antibiotics 2020, 9(11), 785; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9110785 - 07 Nov 2020
Cited by 7 | Viewed by 2446
Abstract
Enterococci are important bacterial pathogens, and their significance is even greater in the case of vancomycin-resistant enterococci (VRE). The study analyzed the presence of VRE in the gastrointestinal tract (GIT) of hemato-oncological patients. Active screening using selective agars yielded VRE for phenotypic and [...] Read more.
Enterococci are important bacterial pathogens, and their significance is even greater in the case of vancomycin-resistant enterococci (VRE). The study analyzed the presence of VRE in the gastrointestinal tract (GIT) of hemato-oncological patients. Active screening using selective agars yielded VRE for phenotypic and genotypic analyses. Isolated strains were identified with MALDI-TOF MS, (Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry) their susceptibility to antibiotics was tested, and resistance genes (vanA, vanB, vanC-1, vanC2-C3) and genes encoding virulence factors (asa1, gelE, cylA, esp, hyl) were detected. Pulsed-field gel electrophoresis was used to assess the relationship of the isolated strains. Over a period of three years, 103 VanA-type VRE were identified in 1405 hemato-oncological patients. The most frequently detected virulence factor was extracellular surface protein (84%), followed by hyaluronidase (40%). Unique restriction profiles were observed in 33% of strains; clonality was detected in 67% of isolates. The study found that 7% of hemato-oncological patients carried VRE in their GIT. In all cases, the species identified was Enterococcus faecium. No clone persisted for the entire 3-year study period. However, genetically different clusters were observed for shorter periods of time, no longer than eight months, with identical VRE spreading among patients. Full article
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