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New Antimicrobial Options in the Clinical Practice of Infections Caused...
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New Antimicrobial Options in the Clinical Practice of Infections Caused by Difficult-to-Treat Pathogens: A Global Opportunity for Public Health

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "The Global Need for Effective Antibiotics".

Deadline for manuscript submissions: closed (31 January 2022) | Viewed by 36063

Special Issue Editor

Dr. Luigi Principe

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Guest Editor
Microbiology and Virology Unit, Great Metropolitan Hospital “Bianchi-Melacrino-Morelli”, Reggio Calabria, Italy
Interests: antimicrobial resistance; antibiotics; resistance mechanisms; difficult-to-treat pathogens; carbapenem resistance; Acinetobacter baumannii
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Antimicrobial resistance (AMR) is a serious cause of concern for public health. Difficult-to-treat pathogens are diffused worldwide, and related infections are associated to the important fatality rate. Recently approved antibiotics represent new weapons in the battle against AMR. This Special Issue considers all aspects of infections related to difficult-to-treat pathogens and antimicrobial options. Moreover, the application of molecular diagnostic and the whole genome sequencing represents an important approach to better understand antimicrobial resistance mechanisms. Articles or reviews regarding pan-drug- (PDR) or extensive drug-resistant (XDR) pathogens, metallo-β-lactamase (MBL)-producing Enterobacterales, Acinetobacter baumannii, Pseudomonas aeruginosa, and vancomycin-resistant Enterococcus are encouraged. In addition, manuscripts concerning specific areas of interest are welcome:

- In vitro and in vivo studies on clinical isolates;

- Case reports or case series;

- Epidemiological and molecular investigation of outbreaks;

- Methods for assaying new antimicrobials;

- Antimicrobial activity of non-antibiotic molecules against clinical isolates;

- Rare or emerging resistance determinants;

- Rare or emerging virulence factors;

- New associations between resistance determinants and pathogens.

Dr. Luigi Principe
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • new antibiotics
  • new antimicrobial options
  • difficult-to-treat pathogens
  • emerging resistance
  • multidrug resistance
  • emerging virulence
  • Acinetobacter baumannii
  • Pseudomonas aeruginosa
  • metallo-β-lactamase-producing enterobacterales
  • vancomycin-resistant Enterococcus

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Published Papers (11 papers)

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Editorial

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4 pages, 179 KiB  
Editorial
New Antimicrobial Options in the Clinical Practice of Infections Caused by Difficult-to-Treat Pathogens: A Global Opportunity for Public Health
by Luigi Principe
Antibiotics 2022, 11(6), 740; https://doi.org/10.3390/antibiotics11060740 - 31 May 2022
Cited by 1 | Viewed by 1830
Abstract
Antimicrobial resistance (AMR) is a serious cause of concern for public health [...] Full article
(This article belongs to the Special Issue New Antimicrobial Options in the Clinical Practice of Infections Caused by Difficult-to-Treat Pathogens: A Global Opportunity for Public Health)

Research

Jump to: Editorial, Review, Other

14 pages, 578 KiB  
Article
Antimicrobial Susceptibility, Virulence, and Genomic Features of a Hypervirulent Serotype K2, ST65 Klebsiella pneumoniae Causing Meningitis in Italy
by Aurora Piazza, Matteo Perini, Carola Mauri, Francesco Comandatore, Elisa Meroni, Francesco Luzzaro and Luigi Principe
Antibiotics 2022, 11(2), 261; https://doi.org/10.3390/antibiotics11020261 - 17 Feb 2022
Cited by 10 | Viewed by 2650
Abstract
The rise of a new hypervirulent variant of Klebsiella pneumoniae (hvKp) was recently reported, mainly linked to the ST23 lineage. The hvKp variants can cause severe infections, including hepatic abscesses, bacteremia, and meningitis, with a particularly disconcerting propensity to cause community-acquired, life-threatening infection [...] Read more.
The rise of a new hypervirulent variant of Klebsiella pneumoniae (hvKp) was recently reported, mainly linked to the ST23 lineage. The hvKp variants can cause severe infections, including hepatic abscesses, bacteremia, and meningitis, with a particularly disconcerting propensity to cause community-acquired, life-threatening infection among young and otherwise healthy individuals. The present study aimed to report the clinical characteristics of a hypermucoviscous K. pneumoniae strain isolated in Italy and sustaining recurrent meningitis in a patient of Peruvian origin. A further objective was to retrospectively investigate, by means of whole-genome sequencing (WGS) analysis, the genomic features of such an isolate. The hypermucoviscosity phenotype of the strain (sk205y205t) was determined using the string test. Genomic information was obtained by WGS (Illumina) and bioinformatic analysis. Strain sk205y205t was susceptible to most antibiotics, despite the presence of some resistance genes, including blaSHV-11, blaSHV-67, fosA, and acrR. The isolate belonged to ST65 and serotype K2, and exhibited several virulence factors related to the hvKp variant. Among these, were the siderophore genes entB, irp2, iroN, iroB, and iucA; the capsule-regulating genes rmpA and rmpA2; and the type 1 and 3 fimbriae fimH27 and mrkD, respectively. A further operon, encoding the genotoxin colibactin (clbA-Q), was also identified. The virulence plasmids pK2044, pRJA166b, and pNDM. MAR were also detected. Phylogenetic investigation showed that this Italian strain is highly similar to a Chinese isolate, suggesting a hidden circulation of this hvKp ST65 K2 lineage. Full article
(This article belongs to the Special Issue New Antimicrobial Options in the Clinical Practice of Infections Caused by Difficult-to-Treat Pathogens: A Global Opportunity for Public Health)
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12 pages, 1895 KiB  
Article
Antimicrobial Activity of Aztreonam in Combination with Old and New β-Lactamase Inhibitors against MBL and ESBL Co-Producing Gram-Negative Clinical Isolates: Possible Options for the Treatment of Complicated Infections
by Gianluca Morroni, Raffaela Bressan, Simona Fioriti, Gloria D’Achille, Marina Mingoia, Oscar Cirioni, Stefano Di Bella, Aurora Piazza, Francesco Comandatore, Carola Mauri, Roberta Migliavacca, Francesco Luzzaro, Luigi Principe and Cristina Lagatolla
Antibiotics 2021, 10(11), 1341; https://doi.org/10.3390/antibiotics10111341 - 3 Nov 2021
Cited by 13 | Viewed by 4139 | Correction
Abstract
Metallo-β-lactamases (MBLs) are among the most challenging bacterial enzymes to overcome. Aztreonam (ATM) is the only β-lactam not hydrolyzed by MBLs but is often inactivated by co-produced extended-spectrum β-lactamases (ESBL). We assessed the activity of the combination of ATM with old and new [...] Read more.
Metallo-β-lactamases (MBLs) are among the most challenging bacterial enzymes to overcome. Aztreonam (ATM) is the only β-lactam not hydrolyzed by MBLs but is often inactivated by co-produced extended-spectrum β-lactamases (ESBL). We assessed the activity of the combination of ATM with old and new β-lactamases inhibitors (BLIs) against MBL and ESBL co-producing Gram-negative clinical isolates. Six Enterobacterales and three non-fermenting bacilli co-producing MBL and ESBL determinants were selected as difficult-to-treat pathogens. ESBLs and MBLs genes were characterized by PCR and sequencing. The activity of ATM in combination with seven different BLIs (clavulanate, sulbactam, tazobactam, vaborbactam, avibactam, relebactam, zidebactam) was assessed by microdilution assay and time–kill curve. ATM plus avibactam was the most effective combination, able to restore ATM susceptibility in four out of nine tested isolates, reaching in some cases a 128-fold reduction of the MIC of ATM. In addition, relebactam and zidebactam showed to be effective, but with lesser reduction of the MIC of ATM. E. meningoseptica and C. indologenes were not inhibited by any ATM–BLI combination. ATM–BLI combinations demonstrated to be promising against MBL and ESBL co-producers, hence providing multiple options for treatment of related infections. However, no effective combination was found for some non-fermentative bacilli, suggesting the presence of additional resistance mechanisms that complicate the choice of an active therapy. Full article
(This article belongs to the Special Issue New Antimicrobial Options in the Clinical Practice of Infections Caused by Difficult-to-Treat Pathogens: A Global Opportunity for Public Health)
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11 pages, 716 KiB  
Article
In Vitro Antimicrobial Activity of the Siderophore Cephalosporin Cefiderocol against Acinetobacter baumannii Strains Recovered from Clinical Samples
by Davide Carcione, Claudia Siracusa, Adela Sulejmani, Roberta Migliavacca, Alessandra Mercato, Aurora Piazza, Luigi Principe, Nicola Clementi, Nicasio Mancini, Valerio Leoni and Jari Intra
Antibiotics 2021, 10(11), 1309; https://doi.org/10.3390/antibiotics10111309 - 27 Oct 2021
Cited by 6 | Viewed by 2794
Abstract
Background: Cefiderocol is a siderophore cephalosporin that exhibits antimicrobial activity against most multi-drug resistant Gram-negative bacteria, including Enterobacterales, Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia. Methods: A total of 20 multidrug-resistant A. baumannii strains were isolated from 2020 to 2021, [...] Read more.
Background: Cefiderocol is a siderophore cephalosporin that exhibits antimicrobial activity against most multi-drug resistant Gram-negative bacteria, including Enterobacterales, Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia. Methods: A total of 20 multidrug-resistant A. baumannii strains were isolated from 2020 to 2021, molecularly characterized and tested to assess the in vitro antibacterial activity of cefiderocol. Thirteen strains were carbapenem-hydrolysing oxacillinase OXA-23-like producers, while seven were non-OXA-23-like producers. Minimum inhibitory concentrations (MICs) were determined by broth microdilution, considered as the gold standard method. Disk diffusion test was also carried out using iron-depleted CAMHB plates for cefiderocol. Results: Cefiderocol MICs ranged from 0.5 to 1 mg/L for OXA-23-like non-producing A. baumannii strains and from 0.25 to >32 mg/L for OXA-23-like producers, using the broth microdilution method. Cefiderocol MIC90 was 8 mg/L. Diameter of inhibition zone of cefiderocol ranged from 18 to 25 mm for OXA-23-like non-producers and from 15 to 36 mm for OXA-23-like producers, using the diffusion disk method. A large variability and a low reproducibility were observed during the determination of diameter inhibition zone. Molecular characterization showed that all isolates presented the ISAba1 genetic element upstream the blaOXA-51. Among OXA-23-like non-producers, four were blaOXA-58 positive and two were negative for all the resistance determinants analyzed. Conclusions: Cefiderocol showed in vitro antimicrobial activity against both carbapenem-susceptible and non-susceptible A. baumannii strains, although some OXA-23-like producers were resistant. Further clinical studies are needed to consolidate the role of cefiderocol as an antibiotic against MDR A. baumannii. Full article
(This article belongs to the Special Issue New Antimicrobial Options in the Clinical Practice of Infections Caused by Difficult-to-Treat Pathogens: A Global Opportunity for Public Health)
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12 pages, 954 KiB  
Article
Heteroaryl-Ethylenes as New Lead Compounds in the Fight against High Priority Bacterial Strains
by Dafne Bongiorno, Nicolò Musso, Paolo G. Bonacci, Dalida A. Bivona, Mariacristina Massimino, Stefano Stracquadanio, Carmela Bonaccorso, Cosimo G. Fortuna and Stefania Stefani
Antibiotics 2021, 10(9), 1034; https://doi.org/10.3390/antibiotics10091034 - 25 Aug 2021
Cited by 4 | Viewed by 2656
Abstract
The widespread use of antibiotics has led to a gradual increase in drug-resistant bacterial infections, which severely weakens the clinical efficacy of antibacterial therapies. In recent decades, stilbenes aroused great interest because of their high bioavailability, as well as their manifold biological activity. [...] Read more.
The widespread use of antibiotics has led to a gradual increase in drug-resistant bacterial infections, which severely weakens the clinical efficacy of antibacterial therapies. In recent decades, stilbenes aroused great interest because of their high bioavailability, as well as their manifold biological activity. Our research efforts are focused on synthetic heteroaromatic stilbene derivatives as they represent a potentially new type of antibiotic with a wide antibacterial spectrum. Herein, a preliminary molecular modeling study and a versatile synthetic scheme allowed us to define eight heteroaromatic stilbene derivatives with potential antimicrobial activity. In order to evaluate our compound’s activity spectrum and antibacterial ability, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) tests have been performed on Gram-positive and Gram-negative ATCC strains. Compounds PB4, PB5, PB7, and PB8 showed the best values in terms of MIC and were also evaluated for MBC, which was found to be greater than MIC, confirming a bacteriostatic activity. For all compounds, we evaluated toxicity on colon-rectal adenocarcinoma cells tumor cells (CaCo2), once it was established that the whole selected set was more active than 5-Fluorouracil in reducing CaCo-2 cells viability. To the best of our knowledge, the biological assays have shown for these derivatives an excellent bacteriostatic activity, compared to similar molecular structures previously reported, thus paving the way for a new class of antibiotic compounds. Full article
(This article belongs to the Special Issue New Antimicrobial Options in the Clinical Practice of Infections Caused by Difficult-to-Treat Pathogens: A Global Opportunity for Public Health)
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17 pages, 1910 KiB  
Article
Whole-Genome Sequencing Investigation of a Large Nosocomial Outbreak Caused by ST131 H30Rx KPC-Producing Escherichia coli in Italy
by Aurora Piazza, Luigi Principe, Francesco Comandatore, Matteo Perini, Elisa Meroni, Vittoria Mattioni Marchetti, Roberta Migliavacca and Francesco Luzzaro
Antibiotics 2021, 10(6), 718; https://doi.org/10.3390/antibiotics10060718 - 15 Jun 2021
Cited by 10 | Viewed by 2406
Abstract
KPC-producing Escherichia coli (KPC-Ec) remains uncommon, being mainly reported as the cause of sporadic episodes of infection rather than outbreak events. Here we retrospectively describe the dynamics of a large hospital outbreak sustained by KPC-Ec, involving 106 patients and 25 hospital wards, during [...] Read more.
KPC-producing Escherichia coli (KPC-Ec) remains uncommon, being mainly reported as the cause of sporadic episodes of infection rather than outbreak events. Here we retrospectively describe the dynamics of a large hospital outbreak sustained by KPC-Ec, involving 106 patients and 25 hospital wards, during a six-month period. Twenty-nine representative KPC-Ec isolates (8/29 from rectal swabs; 21/29 from other clinical specimens) have been investigated by Whole-Genome Sequencing (WGS). Outbreak isolates showed a multidrug-resistant profile and harbored several resistance determinants, including blaCTX-M-27, aadA5, dfrA17, sulI, gyrA1AB and parC1aAB. Phylogenomic analysis identified the ST131 cluster 1 (23/29 isolates), H30Rx clade C, as responsible for the epidemic event. A further two KPC-Ec ST131 clusters were identified: cluster 2 (n = 2/29) and cluster 3 (n = 1/29). The remaining KPC-Ec resulted in ST978 (n = 2/29) and ST1193 (n = 1/29), and were blaKPC-3 associated. The KPC-Ec ST131 cluster 1, originated in a previous KPC-Kp endemic context probably by plasmid transfer, and showed a clonal dissemination strategy. Transmission of the blaKPC gene to the globally disseminated high-risk ST131 clone represents a serious cause of concern. Application of WGS in outbreak investigations could be useful to better understand the evolution of epidemic events in order to address infection control and contrast interventions, especially when high-risk epidemic clones are involved. Full article
(This article belongs to the Special Issue New Antimicrobial Options in the Clinical Practice of Infections Caused by Difficult-to-Treat Pathogens: A Global Opportunity for Public Health)
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10 pages, 406 KiB  
Article
Epidemiology of Meropenem/Vaborbactam Resistance in KPC-Producing Klebsiella pneumoniae Causing Bloodstream Infections in Northern Italy, 2018
by Paolo Gaibani, Donatella Lombardo, Linda Bussini, Federica Bovo, Beatrice Munari, Maddalena Giannella, Michele Bartoletti, Pierluigi Viale, Tiziana Lazzarotto and Simone Ambretti
Antibiotics 2021, 10(5), 536; https://doi.org/10.3390/antibiotics10050536 - 6 May 2021
Cited by 37 | Viewed by 3530
Abstract
Meropenem/Vaborbactam (MEM-VAB) is a novel carbapenem- β-lactamase inhibitor active against KPC-producing Enterobacteria. Herein, we evaluate the incidence of meropenem/vaborbactam-resistance among KPC-producing K. pneumoniae (KPC-Kp) bloodstream infection in a large Italian hospital. Meropenem/vaborbactam-resistance was found in 8% (n = 5) KPC-Kp, while 5% [...] Read more.
Meropenem/Vaborbactam (MEM-VAB) is a novel carbapenem- β-lactamase inhibitor active against KPC-producing Enterobacteria. Herein, we evaluate the incidence of meropenem/vaborbactam-resistance among KPC-producing K. pneumoniae (KPC-Kp) bloodstream infection in a large Italian hospital. Meropenem/vaborbactam-resistance was found in 8% (n = 5) KPC-Kp, while 5% (n = 3) strains exhibited cross-resistance to ceftazidime/avibactam (CAZ-AVI). Genomic analysis revealed that meropenem/vaborbactam-resistance was associated with truncated OmpK35 and insertion of glycine and aspartic acid within OmpK36 at position 134–135 (GD134–135). Notably, no specific mutation was associated to cross-resistance. No specific antimicrobial treatment was related to favorable clinical outcomes, while cross-resistance was not associated to higher clinical and/or microbiological failures. Our study indicated that resistance to meropenem/vaborbactam was due to porins mutations and is associated with reduced susceptibility to both ceftazidime/avibactam and carbapenems. Full article
(This article belongs to the Special Issue New Antimicrobial Options in the Clinical Practice of Infections Caused by Difficult-to-Treat Pathogens: A Global Opportunity for Public Health)
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Review

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11 pages, 1307 KiB  
Review
Ceftobiprole Perspective: Current and Potential Future Indications
by Tommaso Lupia, Carlo Pallotto, Silvia Corcione, Lucio Boglione and Francesco Giuseppe De Rosa
Antibiotics 2021, 10(2), 170; https://doi.org/10.3390/antibiotics10020170 - 8 Feb 2021
Cited by 22 | Viewed by 7072
Abstract
Ceftobiprole combines an excellent spectrum for community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP) pathogens, with a low/medium MDR risk, and the β-lactams’ safety in frail patients admitted to the hospital in internal medicine wards which may be at high risk of adverse events [...] Read more.
Ceftobiprole combines an excellent spectrum for community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP) pathogens, with a low/medium MDR risk, and the β-lactams’ safety in frail patients admitted to the hospital in internal medicine wards which may be at high risk of adverse events by anti-MRSA coverage as oxazolidinones or glycopeptides. We aimed to report the available evidence regarding ceftobiprole use in pneumonia and invasive bacterial infections, shedding light on ceftobiprole stewardship. The clinical application and real-life experiences of using ceftobiprole for bloodstream infections, including infective endocarditis, are limited but nevertheless promising. In addition, extended-spectrum ceftobiprole activity, including Enterococcus faecalis, Enterobacteriaceae, and Pseudomonas aeruginosa, has theoretical advantages for use as empirical therapy in bacteremia potentially caused by a broad spectrum of microorganisms, such as catheter-related bacteremia. In the future, the desirable approach to sepsis and severe infections will be administered to patients according to their clinical situation, the intrinsic host characteristics, the susceptibility profile, and local epidemiology, while the “universal antibiotic strategy” will no longer be adequate. Full article
(This article belongs to the Special Issue New Antimicrobial Options in the Clinical Practice of Infections Caused by Difficult-to-Treat Pathogens: A Global Opportunity for Public Health)
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Other

9 pages, 260 KiB  
Brief Report
XDR-Pseudomonas aeruginosa Outside the ICU: Is There Still Place for Colistin?
by Paola Del Giacomo, Francesca Raffaelli, Angela Raffaella Losito, Barbara Fiori and Mario Tumbarello
Antibiotics 2022, 11(2), 193; https://doi.org/10.3390/antibiotics11020193 - 1 Feb 2022
Cited by 5 | Viewed by 2117
Abstract
Background: Pseudomonas aeruginosa represents, among the nosocomial pathogens, one of the most serious threats, both for the severity of its clinical manifestations and its ability to develop complex profiles of resistance; Methods: we retrospectively collected the data of 21 patients admitted to a [...] Read more.
Background: Pseudomonas aeruginosa represents, among the nosocomial pathogens, one of the most serious threats, both for the severity of its clinical manifestations and its ability to develop complex profiles of resistance; Methods: we retrospectively collected the data of 21 patients admitted to a tertiary-care University Hospital of Rome with infections due to XDR-P. aeruginosa isolates during the second half of 2020; Results: in our institution, the percentage of XDR-P. aeruginosa isolates is 3.1%. None of the patients was admitted to the intensive care unit at the moment of the infection’s onset. Susceptibility to colistin was preserved in all the tested isolates. Rates of resistance to ceftolozane/tazobactam and ceftazidime/avibactam in these XDR strains were consistent; Conclusions: XDR-P. aeruginosa can be a threatening problem even outside the ICUs, especially in frail patients in wards with features of long-term acute care hospitals. In such a setting, ceftolozane/tazobactam and ceftazidime/avibactam should be administered with caution taking into account the microbiological susceptibility results. Colistin, even with its known safety and efficacy limits, could represent the only available therapeutic option due to its highly preserved susceptibility against XDR isolates of P. aeruginosa. Full article
(This article belongs to the Special Issue New Antimicrobial Options in the Clinical Practice of Infections Caused by Difficult-to-Treat Pathogens: A Global Opportunity for Public Health)
8 pages, 1839 KiB  
Brief Report
Direct Testing for KPC-Mediated Carbapenem Resistance from Blood Samples Using a T2 Magnetic Resonance Based Assay
by Giulia De Angelis, Riccardo Paggi, Thomas J. Lowery, Jessica L. Snyder, Giulia Menchinelli, Maurizio Sanguinetti, Brunella Posteraro and Antonella Mencacci
Antibiotics 2021, 10(8), 950; https://doi.org/10.3390/antibiotics10080950 - 6 Aug 2021
Cited by 5 | Viewed by 2579
Abstract
Molecular-based carbapenem resistance testing in Gram-negative bacterial bloodstream infections (BSIs) is currently limited because of the reliance on positive blood culture (BC) samples. The T2Resistance™ panel may now allow the detection of carbapenemase- and other β-lactamase encoding genes directly from blood samples. We [...] Read more.
Molecular-based carbapenem resistance testing in Gram-negative bacterial bloodstream infections (BSIs) is currently limited because of the reliance on positive blood culture (BC) samples. The T2Resistance™ panel may now allow the detection of carbapenemase- and other β-lactamase encoding genes directly from blood samples. We detected carbapenem resistance genes in 11 (84.6%) of 13 samples from patients with BC-documented BSIs (10 caused by KPC-producing Klebsiellapneumoniae and 1 caused by VIM/CMY-producing Citrobacter freundii). Two samples that tested negative for carbapenem resistance genes were from patients with BC-documented BSIs caused by KPC-producing K. pneumoniae who were receiving effective antibiotic therapy. In conclusion, our findings suggest that the T2Resistance™ panel can be a reliable tool for diagnosing carbapenem-resistant Gram-negative bacterial BSIs. Full article
(This article belongs to the Special Issue New Antimicrobial Options in the Clinical Practice of Infections Caused by Difficult-to-Treat Pathogens: A Global Opportunity for Public Health)
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8 pages, 825 KiB  
Case Report
Synergistic Meropenem/Vaborbactam Plus Fosfomycin Treatment of KPC Producing K. pneumoniae Septic Thrombosis Unresponsive to Ceftazidime/Avibactam: From the Bench to the Bedside
by Alessandra Oliva, Ambrogio Curtolo, Lorenzo Volpicelli, Francesco Cogliati Dezza, Massimiliano De Angelis, Sara Cairoli, Donatella Dell’Utri, Bianca Maria Goffredo, Giammarco Raponi and Mario Venditti
Antibiotics 2021, 10(7), 781; https://doi.org/10.3390/antibiotics10070781 - 27 Jun 2021
Cited by 19 | Viewed by 2683
Abstract
Gram-negative bacilli septic thrombosis (GNB-ST) represents a subtle and often misleading condition, potentially fatal if not recognized early and requiring prolonged antimicrobial therapy and anticoagulation. Herein, reported for the first time, is a very challenging case of Klebsiella producing carbapenemase (KPC)-producing K. pneumoniae [...] Read more.
Gram-negative bacilli septic thrombosis (GNB-ST) represents a subtle and often misleading condition, potentially fatal if not recognized early and requiring prolonged antimicrobial therapy and anticoagulation. Herein, reported for the first time, is a very challenging case of Klebsiella producing carbapenemase (KPC)-producing K. pneumoniae (KPC-Kp) ST unresponsive to ceftazidime/avibactam (CZA) relapsed first with meropenem/vaborbactam (MVB) monotherapy and subsequently cured with MVB plus fosfomycin (FOS) combination. The present case highlights the possibility of CZA underexposure on the infected thrombus and the risk of in vivo emergence of CZA resistance in the setting of persistent bacteremia and sub-optimal anticoagulation. Pharmacokinetic analyses showed that both MVB and FOS were in the therapeutic range. In vitro studies demonstrated a high level of MVB + FOS synergism that possibly allowed definitive resolution of the endovascular infection. Full article
(This article belongs to the Special Issue New Antimicrobial Options in the Clinical Practice of Infections Caused by Difficult-to-Treat Pathogens: A Global Opportunity for Public Health)
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