Use 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.
The 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.
The 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.
In 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.
Purpose
To explore whether topical antibiotic prophylaxis in patients scheduled for intravitreal injections achieves surface sterility in a greater proportion of subjects as compared to ...povidone-iodine alone.
Material and methods
A randomized, triple-blind clinical trial. Population: patients scheduled for intravitreal injections for maculopathy. Inclusion criteria: any sex and race, age 18 years and above. Subjects were randomized into 4 groups: the first group applied chloramphenicol (CHLORAM), the second netilmicin (NETILM), the third a commercial ozonized antiseptic solution (OZONE), and the fourth applied no drops (CONTROL). Outcome variable: percentage of non-sterile conjunctival swabs. Specimens were collected before and after the application of 5% povidone-iodine moments before the injection.
Results
Ninety-eight subjects (33.7% females, 64.3% males), mean age: 70.2 ± 9.3 years (54–91). Before povidone-iodine, both the CHLORAM and NETILM group showed a lower percentage of non-sterile swabs (61.1% and 31.3% respectively), as compared to the OZONE (83.3%) and CONTROL (86.5%) groups (
p
< .04). However, this statistical difference was lost after the application of povidone-iodine for 3 min. Percentage of non-sterile swabs in each group after applying 5% povidone-iodine: CHLORAM 11.1%, NETILM 12.5%, CONTROL 15.4%, OZONE 25.0%. This was not statistically significant (
p
> .05).
Conclusions
Topical antibiotic prophylaxis with chloramphenicol or netilmicin drops decreases the bacterial load on the conjunctiva. However, after the application of povidone-iodine, all groups showed a significant reduction in the percentage of non-sterile swabs, and this value was comparable among all groups. For this reason, authors conclude that povidone-iodine alone is sufficient and prior topical antibiotic prophylaxis is not indicated.
Candida osteomyelitis is uncommon, especially after dog bites. We describe a case of a 63-year-old man without significant comorbidities presenting progressing swelling of the distal ...interphalangeal joint (DIJ) of right index finger following a dog bite. Despite empiric antibiotic therapy and local medications, there were no clinical signs of improvement. Clinical examination revealed fistula with purulent drainage on the volar region. Even though laboratory data showed inflammatory markers on range, magnetic resonance imaging (MRI) demonstrated signs of osteomyelitis. The patient was taken to exploration and debridement of the bite wound. Culture of the bone biopsy showed growth of Candida parapsilosis. Therefore, the patient was diagnosed with isolated fungal osteomyelitis and was initiated on fluconazole therapy. The treatment was effective and all symptoms were resolved in 8 weeks after the surgery. There were no signs of recurrence after 20 months of follow-up. The patient had no cosmetic abnormalities or sequelae. Concurrently with the description of the case report a review of the literature was provided.
According to the authors, there are three main etiopathogenesis for this infection. The first pathogenic mechanism is direct inoculation into the deep tissues through the dog bite. The second hypothesis is direct translocation of the pathogen from the skin to the deep tissue and to the bone. The last mode of transmission is hematogenous dissemination. Fungal osteomyelitis are really rare conditions, especially after dog bites, but nevertheless it should be considered as a possible diagnosis when there is no response to antibiotics.
The first reports of carbapenem-resistant
in our hospital date back to 2006. In that period, few ertapenem-resistant but meropenem-susceptible
isolates belonging to sequence type (ST) 37 were ...retrieved from clinical samples. These strains produced the CTX-M-15 extended spectrum β-lactamase, OmpK35 was depleted due to a nonsense mutation, and a novel OmpK36 variant was identified. Yet, starting from 2010,
carbapenemase (KPC)-producing ST512 isolates started prevailing and ST37 vanished from sight. Since 2018 the clinical use of the combination of ceftazidime-avibactam (CZA) has been introduced in clinical practice for the treatment of bacteria producing serine-β-lactamases, but KPC-producing, CZA-resistant
are emerging. In 2021, four CZA-resistant ST37 isolates producing KPC variants were isolated from the same number of patients.
KPC gene cloning in
was used to define the role of those KPC variants on CZA resistance, and whole genome sequencing was performed on these isolates and on three ST37 historical isolates from 2011. CZA resistance was due to mutations in the
KPC genes carried on related pKpQIL-type plasmids, and three variants of the KPC enzyme have been identified in the four ST37 strains. The four ST37 isolates were closely related to each other and to the historical isolates, suggesting that ST37 survived without notice in our hospital for 10 years, waiting to re-emerge as a CZA-resistant
clone. The ancestor of these contemporary isolates derives from ST37 wild-type porin strains, with no other mutations in chromosomal genes involved in conferring antibiotic resistance (
,
,
,
,
).
Adherent bacteria and biofilm frequently colonize central venous catheters (CVCs). CVC colonization is correlated to infections and particularly to bloodstream ones. The classical microbiological ...methods to determine of CVC colonization are not fully reliable and are time-consuming. BioTimer Assay (BTA) is a biological method already used to count bacteria adherent to abiotic surfaces and biofilm without sample manipulation. BTA employs specific reagents whose color changed according to bacterial metabolism. BTA is based on the principle that a metabolic reaction will be faster when more bacteria are present in the sample. Therefore, the time required for color changes of BTA reagents determines the number of bacteria present in the sample through a correlation line. Here, for the first time, we applied BTA and a specifically developed laboratory procedure to evaluate CVC colonization in comparison with the routine microbiological method (RMM). 125 CVCs removed from patients for suspected catheter-related bloodstream infection (CRBSI) or at hospital discharge were examined. BTA was reliable in assessing sterility and CVC colonization (100% agreement with RMM) and in recognizing the presence of fermenting or non-fermenting bacteria (97.1% agreement with RMM) shortening the analytical time by between 2- and 3-fold. Moreover, the reliability of BTA as early alert of CRBSI was evaluated. The sensitivity, specificity, positive, and negative predictive values for BTA as an early alert of CRBSI were 100, 40.0, 88.8 and 100%, respectively.
In conclusion, BTA and the related laboratory procedure should be incorporated into routine microbiological methods since it can be considered a reliable tool to evaluate CVC colonization in a very short time and a rapid alert for CRBSIs.
•Application of BioTimer Assay and a specifically developed laboratory procedure in evaluation of central venous catheter colonization•BioTimer Assay is reliable and faster than the RMM•BioTimer Assay and the related laboratory procedure can be used as a reliable and early alert of CVC-related bloodstream infections•BioTimer Assay and the related laboratory procedure should be incorporated into routine microbiological methods
To analyse the species distribution and the susceptibility profiles to the major antifungal agents of Candida isolated from bloodstream infections (BSIs) in both intensive care units (ICUs) and ...non-ICU wards in a tertiary care hospital in Italy from 2010 until 2015.
Episodes of Candida BSI were recorded in a retrospective observational cohort study. Yeasts were isolated from both blood and intravascuIar devices (IVDs) and their susceptibility to antifungal drugs was tested using the microdilution method.
514 Candida BSIs were evidenced and 19 % of these episodes were associated with the presence of an IVD. The trend of the general incidence increased significantly throughout the study period, ranging from 1.42 to 3.63 (mean 2.52) episodes/1000 admissions. The incidence of Candida BSIs and IVD-associated candidaemia was significantly higher in ICUs relative to the other wards. The most frequently isolated species were C. albicans and C. parapsilosis complex, with the latter presenting a significant increased trend of isolation. C. parapsilosis complex was most frequently involved in IVD-related candidaemia, coinfections and late recurrent infections. Furthermore, the MIC50s of C. parapsilosis complex were significantly enhanced for echinocandins compared to the MIC50s for the same drugs and the other yeasts, while the MIC50s of C. albicans for amphotericin B showed a significant increase during the study period, ranging from 0.1 to 0.5 µg ml-1.
A progressively enhanced incidence of Candida BSIs, a relatively high impact of C. parapsilosis complex and changes in the susceptibility profiles of the isolated yeasts were evidenced during the observation period.
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•Adarotene analogues were synthesized and investigated as antimicrobials.•The compounds exhibited activity against S. aureus strains, including resistant ones.•MD simulations on a ...lipid bilayer membrane systems of S. aureus were run.•A selected candidate showed tolerability on human cell lines and good PK profile.•An enhancement of the growth-inhibitory effect of rifaximin was demonstrated.
Multidrug-resistant (MDR) pathogens are severely impacting our ability to successfully treat common infections. Here we report the synthesis of a panel of adarotene-related retinoids showing potent antimicrobial activity on Staphylococcus aureus strains (including multidrug-resistant ones). Fluorescence and molecular dynamic studies confirmed that the adarotene analogues were able to induce conformational changes and disfunctions to the cell membrane, perturbing the permeability of the phospholipid bilayer. Since the major obstacle for developing retinoids is their potential cytotoxicity, a selected candidate was further investigated to evaluate its activity on a panel of human cell lines. The compound was found to be well tolerated, with IC50 5–15-fold higher than the MIC on S. aureus strains. Furthermore, the adarotene analogue had a good pharmacokinetic profile, reaching a plasma concentration of about 6 μM after 0.5 h after administration (150 mg/kg), at least twice the MIC observed against various bacterial strains. Moreover, it was demonstrated that the compound potentiated the growth-inhibitory effect of the poorly bioavailable rifaximin, when used in combination. Overall, the collected data pave the way for the development of synthetic retinoids as potential therapeutics for hard-to-treat infectious diseases caused by antibiotic-resistant Gram-positive pathogens.
Infections are still the most common complications of cerebral shunt procedures. Even though fungal etiologies are considered to be rare, they are associated with significant morbidity and mortality. ...Due to their uncommonness, diagnostic procedures and optimal therapy are poorly defined. We report a case of Candida tropicalis infection of ventriculo-peritoneal cerebrospinal fluid (CSF) shunt in a 49-year-old immune competent male treated with voriconazole (VOR).
Microbiological and CSF markers (1,3-b-D-glucan-BDG) of fungal infection, biofilm production capacity, sensitivity of serial isolates of the pathogen, and the concentration of the antifungal drug have been monitored and related to the clinical course of this infection.
Despite appropriate treatment with VOR, in terms of adequate achieved CSF drug concentrations and initial effective therapeutic response, loss of VOR susceptibility of the C tropicalis and treatment failure were observed.
Biofilm production of the C. tropicalis isolate might have had a significant role in treatment failure. Of interest, clinical and microbiological unfavorable outcome was anticipated by persistence of BDG in CSF. Rising titers of this marker were associated with relapse of fungal infection.
Several studies have addressed the epidemiology of community-associated Staphylococcus aureus (CA-SA) in Europe; nonetheless, a comprehensive perspective remains unclear. In this study, we aimed to ...describe the population structure of CA-SA and to shed light on the origin of methicillin-resistant S. aureus (MRSA) in this continent.
A total of 568 colonization and infection isolates, comprising both MRSA and methicillin-susceptible S. aureus (MSSA), were recovered in 16 European countries, from community and community-onset infections. The genetic background of isolates was characterized by molecular typing techniques (spa typing, pulsed-field gel electrophoresis and multilocus sequence typing) and the presence of PVL and ACME was tested by PCR. MRSA were further characterized by SCCmec typing. We found that 59% of all isolates were associated with community-associated clones. Most MRSA were related with USA300 (ST8-IVa and variants) (40%), followed by the European clone (ST80-IVc and derivatives) (28%) and the Taiwan clone (ST59-IVa and related clonal types) (15%). A total of 83% of MRSA carried Panton-Valentine leukocidin (PVL) and 14% carried the arginine catabolic mobile element (ACME). Surprisingly, we found a high genetic diversity among MRSA clonal types (ST-SCCmec), Simpson's index of diversity = 0.852 (0.788-0.916). Specifically, about half of the isolates carried novel associations between genetic background and SCCmec. Analysis by BURP showed that some CA-MSSA and CA-MRSA isolates were highly related, suggesting a probable local acquisition/loss of SCCmec.
Our results imply that CA-MRSA origin, epidemiology and population structure in Europe is very dissimilar from that of USA.
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