[The Change in Antimicrobial Resistance During the COVID-19 Pandemic in Türkiye]. / Türkiye'de COVID-19 Pandemi Döneminde Antimikrobiyal Direnç Degisimi.

Antimicrobial resistance (AMR) is one of the most important problems threatening human health worldwide. The impact of the Coronavirus disease-2019 (COVID-19) pandemic on AMR continues to be discussed. Some researchers argue that the pandemic will increase AMR rates, while others suggest the opposite. The aim of this study was to investigate the change in AMR of Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus strains in three cross-sectional periods in Türkiye, the first one before the COVID-19 pandemic, the second and the third one during the pandemic. The change in antibiotic susceptibility in Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus strains isolated from urine, blood, and lower respiratory tract samples of patients hospitalized in intensive care units and wards of hospitals before (November 2019) and during the COVID-19 pandemic (November 2020 and July 2021) was investigated in this study. A total of 17 voluntary hospitals, members of the Antibiotic Susceptibility Surveillance Study Group (ADSI) of the Society for Clinical Microbiology Specialists (KLIMUD), participated in the study. Identification of bacteria was performed with automated bacterial identification systems (VITEK2, bioMérieux, France or Phoenix, BD, USA). Antibiotic susceptibility tests were performed in one center with the Kirby-Bauer disc diffusion method and in other centers with automated antibiotic susceptibility test systems (VITEK2, bioMérieux, France or Phoenix, BD, USA), and the results were evaluated according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. Antibiotic susceptibility ratios were statistically analyzed using either the chi-square or Fisher's exact test. A p-value of < 0.05 was considered statistically significant. Antibiotic susceptibility test results of a total of 4030 strains; 1152, 1139, and 1739 belonging to November 2019, November 2020, and July 2021, respectively; were examined. While cefotaxime and ceftazidime susceptibility rates in E.coli strains increased during the pandemic period compared to previous period (p= 0.04, p= 0.001, respectively); nitrofurantoin sensitivity (p= 0.02) and extended-spectrum beta-lactamase (ESBL) ratios (p< 0.001) were found to be decreased. It was determined that the susceptibility rates of all other examined antimicrobials did not change statistically. It was observed that the susceptibility rates of all antibiotics in K.pneumoniae isolates decreased during the pandemic period, but the ESBL rates increased between 2019-2020 (p= 0.01) and decreased between 2020-2021 (p= 0.02). It was found that ESBL rates increased before and after the pandemic. It was observed that the susceptibility to ciprofloxacin (p= 0.0001), levofloxacin (p= 0.003), and gentamicin (p= 0.005) in S.aureus strains increased during the pandemic period. No significant changes were observed in other antibiotic susceptibility rates. Methicillin resistance of S.aureus (MRSA) strains decreased between 2019-2020 (p= 0.03) and increased again in 2021 (p= 0.04) and returned to the pre-pandemic rate. Our study results suggest that the measures taken to reduce the spread of COVID-19 with the pandemic (such as quarantine practices, increased hand hygiene, mask use, and national/international travel restriction) may reduce the spread of bacteria such as ESBL-producing E.coli and the rate of MRSA, which is considered as a hand hygiene indicator. The increase in the later stages of the pandemic recalls the relaxation in compliance with hand hygiene rules. The decrease in the susceptibility rate of K.pneumoniae isolates to antibiotics and the increase in the ESBL rate may be due to inappropriate and excessive use of antibiotics during the pandemic period. However, we believe that these data should be supported by studies to be conducted nowadays when all the rules and measures are back as if the pandemic has ended.

An outbreak investigation of Burkholderia cepacia infections related with contaminated chlorhexidine mouthwash solution in a tertiary care center in Turkey.

BACKGROUND: We report a nosocomial outbreak caused by Burkholderia cepacia that occurred among six patients admitted in the medical and surgical intensive care unit between 04 March 2019 and 02 April 2019 in Istanbul, Turkey. METHODS: The outbreak investigation was launched on 11 March 2019 five days after the detection of B. cepacia in four different patients. We defined potential reservoirs and started environmental screening. We sampled the liquid solutions used in patient care activities. Pulse-field gel electrophoresis (PFGE) was performed to determine the genetic relatedness of environmental and patient samples. RESULTS: Burkholderia cepacia was isolated in tracheal aspiration cultures of six patients. Three out of six patients developed healthcare-associated pneumoniae due to B. cepacia. Environmental cultures in the ICUs revealed B. cepacia growth in 2% chlorhexidine-gluconate mouthwash solution that been used in the colonized patients as well as in samples obtained from the unused products. PFGE revealed the patient and a specific batch of chlorhexidine mouthwash solution samples had a 96% similarity. CONCLUSION: Contamination of medical solutions used in critical patient care could cause outbreaks and should be detected early by infection control teams.

Frequency and associated factors for carbapenem-non-susceptible Bacteroides fragilis group bacteria colonization in hospitalized patients: Case control study in a university hospital in Turkey.

PURPUSE: The carbapenem-resistant Bacteroides fragilis group (CR-BFG) bacteria have been reported in several countries recently with increasing global attention. The high incidence of CR-BFG isolated from our hospitalized patients has become an important problem. Therefore, we aimed to determine the frequency and associated factors for intestinal colonization by carbapenem-non-susceptible BFG (CNS-BFG) among adult patients hospitalized at intensive care units, neurosurgery and internal medicine wards in our hospital. METHODS: Rectal swabs (n = 1200), collected from 766 patients between February 2014 and March 2015, were inoculated onto kanamycin-vancomycin-leaked blood agar containing 0.125 mg/L meropenem. The isolates were identified by MALDI-TOF MS. Susceptibility testing was performed by agar dilution method. The carbapenemase gene (cfiA) was detected by PCR. Logistic regression analysis was used to evaluate the associated factors for intestinal colonization by CNS-BFG. RESULTS: A total 180 non-duplicate BFG isolates were obtained from 164 patients. Ten different species, including Parabacteroides distasonis (n = 46, 25.6%), and Bacteroides fragilis (n = 30; 16.6%), were identified. Twenty-five percent of the isolates were non-susceptible to meropenem (MIC >2 mg/L). The highest prevalence of meropenem resistant strains (MIC >8 mg/L) was detected among B. fragilis (n = 12), followed by Parabacteroides spp. (n = 4). All but one B. fragilis strains were cfiA gene positive. Hospital admission, increasing Charlson score, use of antibiotics; including carbapenems in past three months, colonization with other accompanying carbapenem-resistant Gram negative bacteria (Enterobacteriaceae, Acinetobacter baumannii and Pseudomonas aeruginosa), and having undergone surgical operations were significantly associated with RCS- BFG colonization. CONCLUSIONS: The high carriage rate of CNS-BFG in hospitalized patients may lead to worse clinical outcomes, such as serious infections and mortality, and deserves attention.

In vitro synergistic activity of fosfomycin in combination with meropenem, amikacin and colistin against OXA-48 and/or NDM-producing Klebsiella pneumoniae.

Objective: Carbapenemase-producing Klebsiella pneumoniae (CPKp) infections are increasing worldwide. We investigated the in vitro synergistic activity of fosfomycin (FOS) with meropenem (MRP), amikacin (AMK) and colistin (COL) against OXA-48 and/or New Delhi metallo-beta-lactamase (NDM)-producing Kp blood isolates. Materials and Methods: Seventeen CPKp blood isolates were studied. The broth microdilution method was used for COL, MRP and AMK susceptibilities, while agar dilution for FOS. Synergy was tested by agar dilution chequerboard technique and also was confirmed by a time-kill assay for FOS/MRP and FOS/COL using three representative isolates that were found to be synergistic. Results: FOS in combination with MRP was found to be the most synergistic (15/17 strains, 88%), while 29% and 41% with AMK and COL, respectively. Antagonism was only determined in 2 isolates with the COL/FOS. Conclusions: The MRP/FOS combination demonstrated synergistic activity against CRKp, especially against the two common enzyme-producing isolates in Turkey (OXA-48 and NDM).

Alterations in AdeS and AdeR regulatory proteins in 1-(1-naphthylmethyl)-piperazine responsive colistin resistance of Acinetobacter baumannii.

Colistin resistant Acinetobacter baumannii strains are of great concern worldwide. However, the role of efflux pumps in colistin resistance needs to be elucidated. We investigated the changes in colistin MICs of 29 colistin resistant A. baumannii isolates in response to resistance-nodulation-division (RND)-type efflux pump inhibitor (EPI) and the alterations in AdeR and AdeS two-component regulatory proteins previously associated with the overproduction of AdeAB. The EPI, 1-(1-naphthylmethyl)-piperazine (NMP), led to significant reductions in colistin MICs. At least one of the following amino acid substitutions was found in AdeS proteins from 18 of the isolates: L172P, A94V, V27I, V32I, G186V, and G164A. Besides, A136V and V120I alterations were identified in AdeR from five isolates. Therefore, EPI-responsive colistin resistance in our isolates is most likely due to the action of an RND-type efflux system. The underlying mechanism of resistance might be the result of certain AdeRS alterations, leading to AdeAB overexpression.

Mucormycosis experience through the eyes of the laboratory.

Background: Mucormycosis is a rare, worldwide fungal infection with high mortality, which mostly affects immunocompromised patients. Compared to large parts of Asia, Europe, and the USA, information on clinical expression and fungal species distribution in mucormycosis in Turkey is limited. Objectives and methods: The main aim of this study was to evaluate the demographic features of mucormycosis cases, identify the isolates at the species level by using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF), compare culture results with histopathological examination and determine the antifungal susceptibility patterns of the pathogens. Results: Between 2016 and 2018, 10 mucormycosis cases (six female, four male; age range: 35-74 years) were evaluated retrospectively. The predominance of the cases were in late autumn and winter. Diabetes mellitus was the most common underlying condition. Seven patients had rhinoorbitocerebral, two had pulmonary and one had cutaneous mucormycosis. By mycological culture and direct microscopic examination nine strains were identified as Rhizopus spp. and one as Mucor spp. Seven of these strains were identified at the species level by MALDI-TOF. Histopathological examination of eight tissues were reported as compatible with mucormycosis. All isolates were resistant to azoles and echinocandins. Two isolates were resistant to Amphotericin B and one was resistant to posaconazole. Surgical debridement combined with antifungal therapy was the main treatment option. The mortality rate was 40% (n = 4) and the mean number of days between the onset of complaints and the initiation of treatment was 9.25. Conclusions: Early, rapid and accurate diagnosis of mucormycosis is of critical importance in the treatment of immunosuppressed patients.

Performance of "RESIST-3 O.K.N. K-SeT" immunochromatographic assay for the detection of OXA-48 like, KPC, and NDM carbapenemases in Klebsiella pneumoniae in Turkey.

In this study, the performance of the "RESIST-3 O.K.N. K-SeT" (Coris BioConcept, Gembloux, Belgium) immunochromatographic assay was evaluated in 132 Klebsiella pneumoniae comprising 102 carbapenem resistant and 30 carbapenem susceptible isolates. Genotypically known isolates of Gram negative bacteria (n=22) including various species were also tested by the assay as controls. The isolates tested by the immunochromatographic assay and also were run PCR for blaKPC, blaIMP, blaVIM, blaNDM, and blaOXA-48. The rates of blaNDM, blaOXA-48, and blaKPC in carbapenem resistant isolates were found at 52.9%, 39.2%, and 2.0%, respectively. Both blaNDM and blaOXA-48 were found in six (5.9%) isolates. The results of the assay showed 100% concordance with those obtained by PCR in 132K. pneumoniae. The agreement between the two methods was found to be identical at the isolate level. The assay also correctly detected all genotypically known isolates of Escherichia coli, Serratia marcescens, Citrobacter freundii, Enterobacter cloacae, K. pneumoniae carrying blaKPC, blaNDM, and/or blaOXA-48. On the other hand, the assay did not exhibit any cross-reaction in control isolates harboring blaIMP and blaVIM. We conclude that the RESIST-3 O.K.N. K-SeT is a reliable, rapid, and user friendly test and we recommend it for routine diagnostic laboratories.

The diagnostic value of soluble urokinase plasminogen activator receptor (suPAR) compared to C-reactive protein (CRP) and procalcitonin (PCT) in children with systemic inflammatory response syndrome (SIRS).

BACKGROUND: The aim of the present study was to determine the diagnostic and prognostic values of suPAR and to compare them to CRP and PCT in pediatric patients with systemic inflammatory response syndrome (SIRS). MATERIAL-METHODS: A prospective case-control study was performed.The study was performed in a tertiary university hospital which has a 649-bed capacity. Patients included 27 children with SIRS and 27 control subjects without any infection or immunosuppressive condition. Blood samples were obtained on the day of admission and on the 4-7th days of the hospital stay. RESULTS: The median (min-max) serum levels of suPAR obtained on the first day of the admission were 10.06 (2.7-57.46) and 2.22 (1.08-5.13) ng/Ml for the SIRS group and control group, respectively. The median serum levels of suPAR in the SIRS group was significantly higher than that in the control group (p < 0.05). The serum suPAR levels was significantly higher in nonsurvivors than in survivors in SIRS group (p < 0.05). In the SIRS group, the area under the receiver operating characteristics curve (AUCROC) for suPAR revealed an optimum cut-off value, sensitivity, specificity, NPV and PPV of 0.978, 3.8 ng/mL, 96%, 96%, 96%, and 96%, respectively. CONCLUSIONS: We conclude that suPAR does have diagnostic value in children with SIRS. Additionally, persistent high serum suPAR level predicts mortality in SIRS in children.

The diagnostic value of soluble urokinase plasminogen activator receptor compared with C-reactive protein and procalcitonin in children with febrile neutropenia.

The aim of the present study was to determine the diagnostic value of soluble urokinase plasminogen activator receptor (suPAR) in pediatric patients with febrile neutropenia. A prospective case-control study was performed. Patients included 29 children with febrile neutropenia (FN) and 27 control subjects without any infection or immunosuppressive condition. Blood samples were obtained on the day of admission and on the 4th to 7th days of the hospital stay. The median (minimum-maximum) serum levels of suPAR obtained on the first day of the admission were 2.08 (0.93-9.42) and 2.22 (1.08-5.13) ng/mL for the FN group and the control group, respectively. The median serum levels of suPAR in the FN and control groups were not significantly different (P = .053). The mean serum suPAR level was significantly higher in nonsurvivors than in survivors in the FN group (P < .05). In the FN group, the area under the receiver operating characteristics curve (AUCROC) for suPAR was 0.546, but no optimum cutoff value, sensitivity, specificity, negative predictive value (NPV), or positive predictive value (PPV) was obtained. We conclude that suPAR is not useful as a diagnostic biomarker in children with febrile neutropenia; however, persistent high serum suPAR level may predict mortality in FN in children.

[Serotype distribution and antibiotic susceptibilities of Streptococcus pneumoniae causing acute exacerbations and pneumonia in children with chronic respiratory diseases]. / Kronik Akciger Hastaligi Olan, Akut Alevlenme ve Pnömoni Tanisi ile Basvuran Çocuklarda Streptococcus pneumoniae Serotip Dagilimi ve Antimikrobiyal Duyarliliklari

This study aimed to investigate serotype distribution and antimicrobial resistance of Streptococcus pneumoniae isolates obtained from children with chronic respiratory diseases admitted to hospital with a diagnosis of acute exacerbations between 2008-2010 at Marmara University Hospital, Istanbul, Turkey. Sixty one S.pneumoniae strains isolated from the respiratory samples of patients were studied for erythromycin, clindamycin, tetracyline, trimethoprim-sulphametoxazole (TMP-SMX), vancomycin, levofloxacin susceptibilities by disk diffusion method; MIC values of penicillin and ceftriaxone were determined by E-test (AB Biodisk, Sweden). Results were evaluated according to the CLSI standards. The erythromycin-clindamycin double disc method was applied for the detection of macrolide resistance phenotypes. The presence of macrolide resistance genes, ermB, mef(A)/(E), ermTR were determined by PCR using specific primers for each gene. The serotypes were determined by multiplex PCR using specific primers for 40 different serotypes. According to CLSI criteria, penicillin resistance in S.pneumoniae isolates were found to be 8.2% (5/61) and intermediate resistance rate was 54% (33/61) for oral penicillin. Penicillin resistance were found to be only 1.6% (1/61) for parenteral penicillin. Resistance rates of erythromycin, clindamycin, tetracyline, TMP-SMX were detected as 55.8%, 46%, 47.5% and 67.2%; respectively. No resistance was detected to vancomycin and levofloxacin. Constitutive macrolide-lincosamide-streptogramin B (cMLSB) phenotype and M phenotype were observed in 82.4% (n= 28) and 17.6% (n= 6) of the macrolide resistant isolates, respectively. Inducible macrolide-lincosamide-streptogramin B (iMLSB) phenotype was not detected. The macrolid resistance genotypes, ermB, mef(A)/(E), were positive 50% and 14.7%; respectively. Both ermB and mef(A)/(E) genes were detected 35.3% of the macrolid resistant isolates. None of the isolates were positive for ermTR gene. The most common S.pneumoniae serotypes were determined as serotype 19F, 23F and 6, furthermore penicillin (34%, 15.7% and 18.4%, respectively) and macrolide (38.2%, 20.6% and 14.7%, respectively) resistance rates of those serotypes were found relatively high. Serotype covarage of 7-, 10-, 13-valent conjugated pneumococcal vaccines and 23-valent pneumococcal vaccine were 65%, 67%, 69%, and 78.6%, respectively. In our country, use of the vaccines with these coverage rates has been observed to be effective in children exposed to intensive use of antibiotics with chronic lung disease.