Antimicrobial Multidrug Resistance: Clinical Implications for Infection Management in Critically Ill Patients.

The increasing incidence of antimicrobial resistance (AMR) worldwide represents a serious threat in the management of sepsis. Due to resistance to the most common antimicrobials prescribed, multidrug-resistant (MDR) pathogens have been associated with delays in adequate antimicrobial therapy leading to significant increases in mortality, along with prolonged hospital length of stay (LOS) and increases in healthcare costs. In response to MDR infections and the delay of microbiological results, broad-spectrum antibiotics are frequently used in empirical antimicrobial therapy. This can contribute to the overuse and misuse of antibiotics, further promoting the development of resistance. Multiple measures have been suggested to combat AMR. This review will focus on describing the epidemiology and trends concerning MDR pathogens. Additionally, it will explore the crucial aspects of identifying patients susceptible to MDR infections and optimizing antimicrobial drug dosing, which are both pivotal considerations in the fight against AMR. Expert commentary: The increasing AMR in ICUs worldwide makes the empirical antibiotic therapy challenging in septic patients. An AMR surveillance program together with improvements in MDR identification based on patient risk stratification and molecular rapid diagnostic tools may further help tailoring antimicrobial therapies and avoid unnecessary broad-spectrum antibiotics. Continuous infusions of antibiotics, therapeutic drug monitoring (TDM)-based dosing regimens and combination therapy may contribute to optimizing antimicrobial therapy and limiting the emergence of resistance.

Recent Advances in Colorimetric Tests for the Detection of Infectious Diseases and Antimicrobial Resistance.

Diagnosis of infection-causing microorganisms with sensitive, rapid, selective and economical diagnostic tests is critical to start the right treatment. With these tests, the spread of infections can be prevented. In addition to that, the detection of antimicrobial resistance also makes a significant contribution to public health. In recent years, different types of diagnostic tests have been developed as alternatives to traditional diagnostic tests used in clinics. In particular, colorimetric tests, which minimize the need for an instrument, have advantages owing to their cost effectiveness, rapid response and naked-eye detection and practical use. In this review, we especially focused on pH indicators and nanomaterial-based colorimetric tests in detection of infection-causing microorganisms and antimicrobial resistance.

The Effect of Mesenchymal Stromal Cells on the Mortality of Patients with Sepsis and Septic Shock: A Promising Therapy.

Purpose: Sepsis and septic shock are the major causes of death in intensive care units. This study aimed to evaluate the clinical safety and efficacy of mesenchymal stem cells (MSCs) in sepsis and septic shock patients. Methods: Ten patients were enrolled in the study. Adipose-derived MSC infusions were given (1 × 106/kg, on the 1st, 3rd, 5th, 7th, and 9th days of therapy) together with standard therapy. Before the MSC applications, blood samples were collected for cytokine assessment (TNF-α, IFN-γ, IL-2, IL-4, IL-6, IL-10). The clinical and laboratory improvements were recorded and compared with control groups selected retrospectively. The clinical trial was registered on 16.03.2022 with the registration number NCT05283317. Results: In the study group, the ages of patients ranged from 22 to 68 years, and APACHE II scores ranged from 14 to 42. In the control group, ages ranged from 22 to 80 years and their APACHE II scores were between 14-35. The survival rate in the study group was 100% on the 14th day whereas it was 70% on the 28th day. A significant decrease in the SOFA score (adjusted), clinical, and laboratory improvements were observed during the MSC administration. However, no significant cytokine level changes were observed. In the control group, the survival rate of 20 patients was 70% on the 14th day, whereas 60% was on the 28th day. While deaths were observed in the control group in the first week of treatment, deaths in the MSCs group were observed between the 15th and 28th days. Conclusion: MSCs treatment may have a positive impact on the survival rates of sepsis during the early phase. However, further randomized controlled studies with a large group of patients are needed. Trial Registration. This trial is registered with ClinicalTrials.gov Identifier: NCT05283317.

Increasing frequency of Pseudomonas aeruginosa infections during tigecycline use.

INTRODUCTION: The widespread use of tigecycline raises the question of increasing infection rates of Pseudomonas aeruginosa (PA) in ICUs which are not affected by this antibiotic. OBJECTIVE: The aim of this study was to determine if treatment with tigecycline is a risk factor for PA infection in ICU patients. METHODOLOGY: A retrospective and observational study was conducted at Erciyes University Hospital, Turkey, between 2008 and 2010. The Erciyes University Hospital is a 1300-bed tertiary care facility. The patients included in this study were hospitalized in four adult ICUs. Patients with PA infections (case group) were compared with patients with nosocomial infection other than PA (control group). RESULTS: A total of 1,167 patients with any nosocomial infections were included in the study. Two hundred and seventy eight (23.8%) of the patients had PA infection during their ICU stay. Fifty nine patients (21.2%) in the case group received tigecycline before developing PA infections, which were found to be significantly more frequent than in the controls (p < 0.01). Multivariate analysis showed that risk factors for PA infection were previous tigecycline use (4 times), external ventricular shunt (4.2 times), thoracic drainage catheter (2.5 times) and tracheostomy (1.6 times). CONCLUSION: Our results contribute to the need for new studies to determine the safety of tigecycline use, especially for the treatment of critically ill patients. Since tigecycline seems to be an alternative for the treatment of multidrug resistant (MDR) microorganisms, rational use of this antibiotic in ICU patients is essential.

In vitro synergism of combinations of colistin with selected antibiotics against colistin-resistant Acinetobacter baumannii.

AIM: The in vitro activity of colistin in combination with sulbactam, netilmicin, and vancomycin against colistin-resistant A. baumannii strains was investigated. Furthermore, the clonal relationship of the strains was analyzed. METHODS: Clonal relationship was investigated using rep-PCR. To screen for synergysm, the fractional inhibitory concentration index (FICI) was calculated using checkerboard assay. The killing kinetics of the combination of colistin with vancomycin was assessed using time-kill assay. RESULTS: Three different clones were found among 10 clinical isolates of colistin-resistant A. baumannii strains. Thereof, 8 strains were susceptible to netilmicin. Synergistic interaction was detected in 1 strain with the combination of colistin-netilmicin, in 5 strains with colistin-sulbactam, and in 9 strains with colistin-vancomycin. None of combinations had antagonistic activity. Colistin-vancomycin combination resulted in rapid bactericidal activity. CONCLUSION: These results show a distinct in vitro synergism between colistin and vancomycin, which might be useful to treat infection with multiple-resistant strains, prevent emergence of resistant strains, and to lower doses for both antibiotics to be used.

Do we really need ribavirin in the treatment of crimean-congo hemorrhagic Fever?

The role of ribavirin in the treatment of Crimean-Congo hemorrhagic fever (CCHF) is scarce. We retrospectively reviewed treatment features of 81 hospitalized patients with laboratory confirmed CCHF between January 2007 and December 2010. The median age of the patients was 45 years and 47 were male. Out of 81 patients, 6 received ribavirin. Demographic characteristics and laboratory findings of the patients who received ribavirin were not different from the patients who did not receive antiviral. There were no statistically significant difference in duration of symptoms before admission (P = 0·47) between the two groups. Of the patients, 29 who did not receive ribavirin and four from the ribavirin treated group had severe disease based on the Swanpoel criteria (P = 0·22). Two patients from each group died. There was no statistically significant difference in case fatality (P = 0·14) and duration of hospitalization (P = 0·11). Treatment of CCHF without ribavirin seems to be safe based on the findings of this study.

Use of high-dose IV and aerosolized colistin for the treatment of multidrug-resistant Acinetobacter baumannii ventilator-associated pneumonia: do we really need this treatment?

In this study we aimed to assess the safety and efficacy of high-dose IV colistin (COL) and aerosolized COL for the treatment of Acinetobacter baumannii ventilator-associated pneumonia (VAP). Critically ill adult patients who received IV COL for multidrug-resistant A. baumannii VAP were evaluated retrospectively. A total of 45 patients were evaluated [15 patients with high-dose COL (2.5 mg/kg every 6 h), 20 patients with normal dose (2.5 mg/kg every 12 h), and 10 patients with low dose, determined according to creatine clearance]. Aerosolized COL was used in 29 patients treated with parenteral COL and 16 patients received only parenteral COL. The clinical response rates on the fifth day were 50, 30, and 27 % with the normal, low, and high doses, respectively. However, the clinical response rates at the end of the therapy had declined to 30, 30, and 7 % with the normal, low, and high doses, respectively. The bacteriological clearance rates at the end of the therapy were 65, 75, and 64 %, with the normal, low, and high doses, respectively. With the aerosolized COL, the clinical response rates on the fifth day and at the end of the therapy were 35 and 14 %, whereas these rates were 44 and 38 % without the aerosolized COL. Bacteriological clearance rates with and without the aerosolized COL were 76 and 69 %, respectively. The nephrotoxicity rate was 40 % for the high-dose COL, whereas it was 35 % for the normal dose, and 20 % for the low-dose COL. In conclusion, higher doses of COL and aerosolized COL had no advantages over lower doses in alleviating multidrug-resistant A. baumannii VAP. Moreover, the higher doses and the aerosolized COL increased the nephrotoxicity risk and seemed not to be safe.

Changing pattern of antibiotic susceptibility in intensive care units: ten years experience of a university hospital.

The study was performed to assess microorganisms and antibiotic susceptibility patterns during ten years in intensive care units of a University Hospital. Infection Control Committee has active, prospective surveillance in ICUs for thirteen years. Ten years data of ICUs was evaluated retrospectively from surveillance forms. Microorganisms and their antibiotic resistance were recorded according to the years. During ten years, gram negative microorganisms were the most frequent isolated microorganisms from clinical specimens. Acinetobacter baumannii (21.8%), Pseudomonas aerigunosa (16%), Escherichia coli (10.4%) and Klebsiella pneumoniae (8%) were the most common gram negative microorganisms. However, Staphylococcus aureus was the most prevalent gram positive microorganism, the incidence decreased from 18.6% to 4.8% during ten years. Also antibiotic susceptibility of microorganisms changed during ten years. Carbapenem resistance increased from 44% to 92% in A. baumannii and ciprofloxacin resistance increased in E. coli from 28% to 60% and in K. pneumoniae from 21% to 55% during ten years. However, methicilin resistance decreased in S. aureus from 96% to 54%. In conclusion, antibiotic resistance is growing problem in ICUs. Rationale antibiotic policies and infection control measures will prevent the development of resistance.