PMID- 36140047
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220928
IS  - 2079-6382 (Print)
IS  - 2079-6382 (Electronic)
IS  - 2079-6382 (Linking)
VI  - 11
IP  - 9
DP  - 2022 Sep 18
TI  - Homocysteine and Inflammatory Cytokines in the Clinical Assessment of Infection 
      in Venous Leg Ulcers.
LID - 10.3390/antibiotics11091268 [doi]
LID - 1268
AB  - Inflammation and biofilm-associated infection are common in chronic venous leg 
      ulcers (VU), causing deep pain and delayed healing. Albeit important, clinical 
      markers and laboratory parameters for identifying and monitoring persistent VU 
      infections are limited. This study analyzed 101 patients with infected (IVU) and 
      noninfected VUs (NVU). Clinical data were collected in both groups. The serum 
      homocysteine (Hcys) and inflammatory cytokines from the wound fluid were 
      measured. In addition, microbial identification, antibiotic susceptibility, and 
      biofilm production were examined. IVU were 56 (55.4%) while NVU were 45 (44.5%). 
      IVUs showed a significant increase in the wound's size and depth compared to 
      NVUs. In addition, significantly higher levels of interleukin (IL)-6, IL-10, 
      IL17A, and tumor necrosis factor-alpha (TNF-alpha) were found in patients with IVUs 
      compared to those with NVUs. Notably, hyperhomocysteinemia (HHcy) was 
      significantly more common in patients with IVUs than NVUs. A total of 89 
      different pathogens were identified from 56 IVUs. Gram-negative bacteria were 
      51.7%, while the Gram-positives were 48.3%. At the species level, Staphylococcus 
      aureus was the most common isolate (43.8%), followed by Pseudomonas aeruginosa 
      (18.0%). Multidrug-resistant organisms (MDROs) accounted for 25.8% of the total 
      isolates. Strong biofilm producers (SBPs) (70.8%) were significantly more 
      abundant than weak biofilm producers (WBP) (29.2%) in IVUs. SBPs were present in 
      97.7% of the IVUs as single or multispecies infections. Specifically, SBPs were 
      94.9% for S. aureus, 87.5% for P. aeruginosa, and 28.6% for Escherichia coli. In 
      IVU, the tissue microenvironment and biofilm production can support chronic 
      microbial persistence and a most severe clinical outcome even in the presence of 
      an intense immune response, as shown by the high levels of inflammatory 
      molecules. The measurement of local cytokines in combination with systemic 
      homocysteine may offer a novel set of biomarkers for the clinical assessment of 
      IVUs caused by biofilm-producing bacteria.
FAU - Cavallo, Ilaria
AU  - Cavallo I
AD  - Microbiology and Virology, San Gallicano Dermatological Institute, IRCCS, 00144 
      Rome, Italy.
FAU - Lesnoni La Parola, Ilaria
AU  - Lesnoni La Parola I
AD  - Department of Dermatology, San Gallicano Dermatological Institute, IRCCS, 00144 
      Rome, Italy.
FAU - Sivori, Francesca
AU  - Sivori F
AD  - Microbiology and Virology, San Gallicano Dermatological Institute, IRCCS, 00144 
      Rome, Italy.
FAU - Toma, Luigi
AU  - Toma L
AD  - Department of Research, Advanced Diagnostics, and Technological Innovation, 
      Translational Research Area, IRCCS Regina Elena National Cancer Institute, 00144 
      Rome, Italy.
FAU - Koudriavtseva, Tatiana
AU  - Koudriavtseva T
AD  - Medical Direction, IRCCS Regina Elena National Cancer Institute, 00144 Rome, 
      Italy.
FAU - Sperduti, Isabella
AU  - Sperduti I
AD  - Biostatistics, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy.
FAU - Kovacs, Daniela
AU  - Kovacs D
AD  - Cutaneous Physiopathology, San Gallicano Dermatological Institute, IRCCS, 00144 
      Rome, Italy.
FAU - D'Agosto, Giovanna
AU  - D'Agosto G
AD  - Microbiology and Virology, San Gallicano Dermatological Institute, IRCCS, 00144 
      Rome, Italy.
FAU - Trento, Elisabetta
AU  - Trento E
AD  - Microbiology and Virology, San Gallicano Dermatological Institute, IRCCS, 00144 
      Rome, Italy.
FAU - Cameli, Norma
AU  - Cameli N
AD  - Department of Dermatology, San Gallicano Dermatological Institute, IRCCS, 00144 
      Rome, Italy.
FAU - Mussi, Anna
AU  - Mussi A
AD  - Department of Dermatology, San Gallicano Dermatological Institute, IRCCS, 00144 
      Rome, Italy.
FAU - Latini, Alessandra
AU  - Latini A
AD  - Department of Dermatology, San Gallicano Dermatological Institute, IRCCS, 00144 
      Rome, Italy.
FAU - Morrone, Aldo
AU  - Morrone A
AD  - Scientific Direction, San Gallicano Institute, IRCCS, 00144 Rome, Italy.
FAU - Pimpinelli, Fulvia
AU  - Pimpinelli F
AUID- ORCID: 0000-0002-8321-4455
AD  - Microbiology and Virology, San Gallicano Dermatological Institute, IRCCS, 00144 
      Rome, Italy.
FAU - Di Domenico, Enea Gino
AU  - Di Domenico EG
AUID- ORCID: 0000-0001-6295-6006
AD  - Department of Biology and Biotechnology "C. Darwin", Sapienza University, 00185 
      Rome, Italy.
LA  - eng
PT  - Journal Article
DEP - 20220918
PL  - Switzerland
TA  - Antibiotics (Basel)
JT  - Antibiotics (Basel, Switzerland)
JID - 101637404
PMC - PMC9495878
OTO - NOTNLM
OT  - biofilm
OT  - cytokines
OT  - homocysteine
OT  - infection
OT  - leg ulcers
OT  - venous ulcer
OT  - wound
COIS- The authors declare no conflict of interest.
EDAT- 2022/09/24 06:00
MHDA- 2022/09/24 06:01
PMCR- 2022/09/18
CRDT- 2022/09/23 01:09
PHST- 2022/08/12 00:00 [received]
PHST- 2022/09/07 00:00 [revised]
PHST- 2022/09/16 00:00 [accepted]
PHST- 2022/09/23 01:09 [entrez]
PHST- 2022/09/24 06:00 [pubmed]
PHST- 2022/09/24 06:01 [medline]
PHST- 2022/09/18 00:00 [pmc-release]
AID - antibiotics11091268 [pii]
AID - antibiotics-11-01268 [pii]
AID - 10.3390/antibiotics11091268 [doi]
PST - epublish
SO  - Antibiotics (Basel). 2022 Sep 18;11(9):1268. doi: 10.3390/antibiotics11091268.