IntroductionUse of colistin methanesulfonate (CMS) was abandoned in the 1970s because of excessive nephrotoxicity, but it has been reintroduced as a last-resort treatment for extensively drug-resistant infections caused by gram-negative bacteria (Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumonia). We conducted a retrospective cohort study to evaluate risk factors for new-onset acute kidney injury (AKI) in critically ill patients receiving high intravenous doses of colistin methanesulfonate and/or other nephrotoxic antibiotics.MethodsThe cohort consisted of 279 adults admitted to two general ICUs in teaching hospitals between 1 April 2009 and 30 June 2011 with 1) no evidence on admission of acute or chronic kidney disease; and 2) treatment for more than seven days with CMS and/or other nephrotoxic antimicrobials (NAs, that is, aminoglycosides, glycopeptides). Logistic regression analysis was used to identify risk factors associated with this outcome.ResultsThe 279 cases that met the inclusion criteria included 147 patients treated with CMS, alone (n = 90) or with NAs (n = 57), and 132 treated with NAs alone. The 111 (40%) who developed AKI were significantly older and had significantly higher Simplified Acute Physiology Score II (SAPS II) scores than those who did not develop AKI, but rates of hypertension, diabetes mellitus and congestive heart failure were similar in the two groups. The final logistic regression model showed that in the 147 patients who received CMS alone or with NAs, onset of AKI during the ICU stay was associated with septic shock and with SAPS II scores ≥43. Similar results were obtained in the 222 patients treated with CMS alone or NAs alone.ConclusionsIn severely ill ICU patients without pre-existing renal disease who receive CMS high-dose for more than seven days, CMS therapy does not appear to be a risk factor for this outcome. Instead, the development of AKI was strongly correlated with the presence of septic shock and with the severity of the patients as reflected by the SAPS II score.

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The Ralstonia spp . genus is a group of non-fermentative, Gram-negative bacteria often resistant to many antibiotics, which are emerging as opportunistic pathogens frequently associated with infections in hospital settings. We present herein a case of combined R. pickettii and R. mannitolilytica persisting and relapsing bacteraemia, possibly caused by a septic arterial thrombosis secondary to the rupture of an internal carotid artery aneurysm. Microbiology studies showed that both Ralstonia isolates produced biofilm and carried class D oxacillinase genes. When confronted with infections caused by members of the Ralstonia genus, identification to the species level is crucial for correct clinical management, as the two species show different antibiotic susceptibility patterns.

From January 2019 to April 2020, 32 KPC-producing, ceftazidime-avibactam (CZA) resistant Klebsiella pneumoniae strains were isolated in a university hospital in Rome, Italy. These strains belonged to the ST512, ST101 and ST307 high-risk clones. Nine different CZA-resistant KPC-3 protein variants were identified, five of them never previously reported (KPC-66 to KPC-70). Among them, KPC-31, KPC-39, KPC-49, KPC-66, KP-68, KPC-69 and KPC-70 showed amino acid substitutions, insertions and deletions in the Ω loop of the protein. KPC-29 has the duplication, while the novel KPC-67 has the triplication of the KDD triplet in the 270-loop of the protein. Genomics performed on contemporary resistant and susceptible clones underlined that those novel mutations emerged in bla KPC-3 genes located on conserved plasmids: in ST512, all bla KPC-3 mutant genes were located in pKpQIL plasmids, while the three novel bla KPC-3 mutants identified in ST101 were on FIIk-FIA(HI1)-R plasmids. Selection also promoted multiplication of the carbapenemase gene copy number by transposition, recombination, and fusion of resident plasmids. When expressed in Escherichia coli recipient cells cloned in the high-copy number pTOPO vector, the Ω loop mutated variants showed CZA-resistant phenotype associated with susceptibility to carbapenems, while KPC variants with insertions in the 270-loop showed residual activity on carbapenems. The investigation of CZA-resistance mechanisms offered the unique opportunity to study vertical, horizontal, and oblique evolutionary trajectories of K. pneumoniae high-risk clones.

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Teicoplanin has a potential antiviral activity expressed against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was suggested as a complementary option to treat coronavirus disease 2019 (COVID-19) patients. In this multicentric, retrospective, observational research the aim was to evaluate the impact of teicoplanin on the course of COVID-19 in critically ill patients. Fifty-five patients with severe COVID-19, hospitalized in the intensive care units (ICUs) and treated with best available therapy were retrospectively analysed. Among them 34 patients were also treated with teicoplanin (Tei-COVID group), while 21 without teicoplanin (control group). Crude in-hospital Day-30 mortality was lower in Tei-COVID group (35.2%) than in control group (42.8%), however not reaching statistical significance (p = .654). No statistically significant differences in length of stay in the ICU were observed between Tei-COVID group and control group (p = .248). On Day 14 from the ICU hospitalization, viral clearance was achieved in 64.7% patients of Tei-COVID group and 57.1% of control group, without statistical difference. Serum C-reactive protein level was significantly reduced in Tei-COVID group compared to control group, but not other biochemical parameters. Finally, Gram-positive were the causative pathogens for 25% of BSIs in Tei-COVID group and for 70.6% in controls. No side effects related to teicoplanin use were observed.Despite several limitations require further research, in this study the use of teicoplanin is not associated with a significant improvement in outcomes analysed. The antiviral activity of teicoplanin against SARS-CoV-2, previously documented, is probably more effective at early clinical stages.

The influence of five antibiotics (netilmicin, ceftriaxone, cefepime, fleroxacin, and ciprofloxacin) on capsular polysaccharide distribution and on opsonophagocytosis by human polymorphonuclear leukocytes of unencapsulated and encapsulated Escherichia coli strains was studied. Unencapsulated E. coli strains were readily opsonized in serum and easily ingested by polymorphonuclear leukocytes, and antibiotics did not further enhance the phagocytosis rates. In contrast, encapsulated bacteria were poorly opsonized in human serum, and phagocytosis was enhanced after overnight exposure to O.5x the MICs of the antibiotics, with the exception of cefepime. Incubation of unencapsulated as well as encapsulated bacteria in complement-inactivated serum markedly reduced the bacterial uptake by polymorphonuclear leukocytes regardless of the presence of antibiotics. Slide agglutination assays, performed either with a monoclonal antibody for capsular polysaccharide or with an antiserum raised against the stable unencapsulated mutant E. coli 07:K-, showed reduction but not lack of the capsular polysaccharide of encapsulated E. coli 07:K1, and better exposure of subcapsular epitopes, after incubation with 0.5 x the MICs of antibiotics. Flow cytometric analysis of encapsulated E. coli exposed to netilmicin, ciprofloxacin, and fleroxacin revealed that the reduction in capsular material was homogeneous among the bacterial population. Treatment with cefepime and ceftriaxone induced two populations of bacteria that differed in the amount of K antigen present. These results indicate that sub-MICs of netilmicin, ceftriaxone, fleroxacin, and ciprofloxacin influenced complement-mediated opsonization, probably due to changes in the capsular polysaccharide structure.The outer structures of bacteria play an important role in the interaction between bacteria and host defenses during infections. Encapsulated strains of Escherichia coli have been shown to be resistant to the lytic and opsonic activities of serum (6, 7) and to phagocytosis by human polymorphonuclear leukocytes (PMN) (8). The invasive capacity of these bacteria is correlated to their ability to resist killing by normal human serum (9,14). Especially Kl capsule appears to be responsible for serum resistance of strains that are otherwise exquisitely sensitive to the action of serum (2) and that are easily ingested and degraded by PMN (21). However, during infection bacteria are exposed not only to the defense mechanisms of the host but also to the action of antimicrobial agents. It is well known that antibiotics exert part of their action in the body fluids, at concentrations below the MICs. Sub-MICs of certain antibiotics have been shown to modify the morphological and ultrastructural characteristics of bacteria, influencing the interactions with host defense mechanisms, i.e., opsonophagocytosis (5, 15). In previous studies we reported that preexposure of encapsulated E. coli strains to sub-MICs of an aminoglycoside (netilmicin) and of a cephalosporin (ceftriaxone) enhanced the phag...

Head and neck cancer (HNC) concerns more than 890,000 patients worldwide annually and is associated with the advanced stage at presentation and heavy outcomes. Alcohol drinking, together with tobacco smoking, and human papillomavirus infection are the main recognized risk factors. The tumorigenesis of HNC represents an intricate sequential process that implicates a gradual acquisition of genetic and epigenetics alterations targeting crucial pathways regulating cell growth, motility, and stromal interactions. Tumor microenvironment and growth factors also play a major role in HNC. Alcohol toxicity is caused both directly by ethanol and indirectly by its metabolic products, with the involvement of the oral microbiota and oxidative stress; alcohol might enhance the exposure of epithelial cells to carcinogens, causing epigenetic modifications, DNA damage, and inaccurate DNA repair with the formation of DNA adducts. Long-term markers of alcohol consumption, especially those detected in the hair, may provide crucial information on the real alcohol drinking of HNC patients. Strategies for prevention could include food supplements as polyphenols, and alkylating drugs as therapy that play a key role in HNC management. Indeed, polyphenols throughout their antioxidant and anti-inflammatory actions may counteract or limit the toxic effect of alcohol whereas alkylating agents inhibiting cancer cells’ growth could reduce the carcinogenic damage induced by alcohol. Despite the established association between alcohol and HNC, a concerning pattern of alcohol consumption in survivors of HNC has been shown. It is of primary importance to increase the awareness of cancer risks associated with alcohol consumption, both in oncologic patients and the general population, to provide advice for reducing HNC prevalence and complications.