Country data on AMR in Türkiye in the context of community-acquired respiratory tract infections: links between antibiotic susceptibility, local and international antibiotic prescribing guidelines, access to medicine and clinical outcome.

BACKGROUND: Antimicrobial resistance (AMR) is one of the biggest threats to global public health. Selection of resistant bacteria is driven by inappropriate use of antibiotics, amongst other factors. COVID-19 may have exacerbated AMR due to unnecessary antibiotic prescribing. Country-level knowledge is needed to understand options for action. OBJECTIVES: To review AMR in Türkiye and initiatives addressing it. Identifying any areas where more information is required will provide a call to action to minimize any further rise in AMR within Türkiye and to improve patient outcomes. METHODS: National AMR initiatives, antibiotic use and prescribing, and availability of susceptibility data, particularly for the key community-acquired respiratory tract infection (CA-RTI) pathogens Streptococcus pneumoniae and Haemophilus influenzae, were identified. National and international antibiotic prescribing guidelines commonly used locally for specific CA-RTIs (community-acquired pneumonia, acute otitis media, acute bacterial rhinosinusitis) were also reviewed, plus local antibiotic availability. Insights from both a local clinician and local clinical microbiologist were sought to contextualize this information. CONCLUSIONS: Türkiye developed an antibiotic stewardship programme, The Rational Drug Use National Action Plan 2014-2017, prioritizing appropriate antibiotic prescription in the community. Public campaigns discouraging inappropriate antibiotic use were also initiated. Türkiye has a high level of antibiotic resistance and a high level of consumption, however, in 2015 over-the-counter antibiotic sales were prohibited, resulting in a declining trend in overall consumption. There is still a need for physician education on current developments in antibiotic use. Several ongoing global surveillance studies provide antibiotic susceptibility data in Türkiye. Clinicians in Türkiye use several country-specific guidelines for common CA-RTIs plus a range of international guidelines. A more standardized inclusive approach in developing local guidelines, using up-to-date surveillance data on isolates from community-acquired infections in Türkiye, could make guideline use more relevant for clinicians. This would pave the way for a higher level of appropriate antibiotic prescribing and improved adherence. This would, in turn, potentially limit AMR development and improve patient outcome.

Relationship between HLA molecules and late restenosis after coronary stent placement.

OBJECTIVE: The objective of this study is to confirm whether there is relation between the human leucocyte antigen (HLA) locus and restenosis after percutaneous coronary intervention (PCI) holds in our patient population and whether it can be useful as a prognostic factor. METHODS: We examined the HLA phenotypes in 46 consecutive patients (39 men, 7 women, mean age of 57 ± 9 years) who had successful stent implantation in the coronary artery. Selective coronary arteriography was performed 6 months after coronary stenting to assess the presence of restenosis. The HLA phenotyping was performed for HLA-A,-B,-C antigens by Terasaki microlymphocytotoxicity technique and for HLA-DR alleles with PCR-SSP technique. RESULTS: Restenosis(R+) was present in 12 (26.1%) patients (11 men, 1 woman, mean age of 57 ± 10 years). For HLA Class I antigens frequency of HLA-B62 and HLA-CW2 antigen was slightly higher in restenotic patients but did not reach statistical significance. For HLA-DR alleles restenotic patients had higher frequencies for HLA-DRB1(∗)01(R+ %25, R- %14.7), and HLA-DR11(R+ %41.7, R- %20.6), without reaching statistical significance and lower frequencies for DR7(R+ %0, R- %17.6) and D13(R+%8.3, R- %32.4) and HLA-DR53 (R+ %25, R- %35.3) without reaching statistical significance. CONCLUSION: In conclusion, results show that there was no relationship between the development of restenosis and HLA-subtypes.

Impact of HLA on the underlying primary diseases in Turkish patients with end-stage renal disease.

The number of patients with end stage renal disease (ESRD) is increasing faster than the number of renal transplantations performed per year worldwide. Of the primary diseases leading to ESRD, diabetic nephropathy is the leading cause. The purpose of the present study is to investigate the association of HLA with the primary diseases leading to ESRD in Turkish patients. A total of 3230 individuals comprising 587 ESRD patients and 2643 healthy controls were enrolled into the study. Class I HLA-A, -B typing was performed by CDC method, while class II HLA-DRB1 typing was performed by low resolution PCR-SSP. We found a significant negative association between almost all A locus antigens and primary disease groups classified as chronic glomerulonephritis and hypertensive nephrosclerosis (p < 0.05). HLA-B58 and HLA-DRB1*03 significantly correlated with amyloidosis and diabetic nephropathy, respectively. Determination of HLAs as risk factors for primary diseases leading to ESRD might be beneficial in preventing progression to ESRD and recurrence of the primary disease post-transplantation.

Role of procalcitonin, C-reactive protein, interleukin-6, interleukin-8 and tumor necrosis factor-alpha in the diagnosis of neonatal sepsis.

Diagnosis of neonatal sepsis may be difficult because clinical presentations are often nonspecific, bacterial cultures are time-consuming and other laboratory tests lack sensitivity and specificity. In this study, we aimed to investigate the role of procalcitonin (PCT), C-reactive protein (CRP), interleukin (IL)-6, IL-8 and tumor necrosis factor-alpha (TNF-alpha) in establishing the diagnosis and evaluating the prognosis of neonatal sepsis. Twenty-six neonates with blood-culture positivity and clinical sepsis, hospitalized for clinical suspicion of neonatal sepsis in neonatal intensive care units of Balcali Hospital, Cukurova University and Adana State Hospital between May 2000 and January 2001 (Group I) and 29 healthy neonates followed at the neonatal units and outpatient clinics of these hospitals (Group II) in the same period were studied. Among the septic neonates, 13 had early-onset (Group Ia) and 13 had late-onset (Group Ib) neonatal sepsis, while 14 of the healthy neonates had perinatal risk factors (Group IIa) and 15 of them had no risk factors (Group IIb). The demographic and clinical characteristics of the septic and healthy neonates were recorded, blood samples for determining serum PCT, CRP, IL-6, IL-8 and TNF-alpha were collected from the healthy and the septic neonates before starting treatment, and these investigations were repeated on the 3rd and 7th days of treatment. In this study, it was found that: (a) pre-treatment mean serum PCT, CRP, IL-6, IL-8 and TNF-alpha levels were significantly higher in the septic neonates than in the healthy ones, (b) compared with the pre-treatment values, serum PCT, IL-6 and TNF-alpha had progressively decreased on the 3rd and 7th days of the treatment in the 17 recovered patients, though they progressively increased in nine patients who died during treatment, (c) the area under the receiver operating characteristic (ROC) curve (AUC) for PCT, TNF-alpha, IL-6, CRP, and IL-8 were 1.00, 1.00, 0.97, 0.90 and 0.68, respectively. For the cut-off value of PCT > or = 0.34 ng/ml, the test was found to have a sensitivity of 100%, specificity of 96.5%, positive predictive value of 96.2%, negative predictive value of 100% and diagnostic efficacy of 98.3% for bacterial sepsis in neonates. For the cut-off value of TNF-alpha > or = 7.5 pg/ml, sensitivity, specificity, positive predictive value, negative predictive value and diagnostic efficacy were found to be 100%, 96.6%, 96.2%, 96.5% and 98.3%, respectively. It was detected that sensitivity, specificity and diagnostic efficacy values were lower for IL-6, CRP and IL-8. We conclude that PCT and TNF-alpha are the best markers in the diagnosis of neonatal sepsis, and these markers are also valuable in following the effectiveness of treatment and determining the prognosis of the disease.

Do procalcitonin and C-reactive protein levels have a place in the diagnosis and follow-up of Helicobacter pylori infections?

The aims of this study were to determine the levels of procalcitonin (PCT) and C-reactive protein (CRP) in Helicobacter pylori-positive (HP+) patients diagnosed with duodenal and gastric ulcer and to evaluate the correlation of PCT and CRP levels with other invasive and non-invasive diagnostic methods for determination of H. pylori eradication in post-treatment follow-up. Thirty-five HP+ patients with dyspepsia were included in this study. Serum samples (5 ml) were collected at admission and after 24 h. Antimicrobial therapy (omeprazole, amoxycillin and clarithromycin) was given for 1 week to HP+ patients who were positive only by culture or by urease test plus pathology. After 1 month, serum samples (5 ml) were collected again and culture, urease and pathology investigations were performed on endoscopic samples. PCT and CRP levels were measured in the collected blood samples. Thirty-five H. pylori-negative (HP-) cases with dyspepsia, 38 cases with bacteraemia and 35 healthy blood donors were included in this study as control groups. The mean and minimum-maximum levels of PCT were 1.39 (0.25-6.75), 0.35 (0.12-0.71), 7.45 (0.68-51.5) and 0.40 (0.12-0.71) ng ml(-1) for the groups of HP+, HP- and bacteraemia patients and healthy donors, respectively. Mean CRP levels were 1.00 (<0.5-8.11), 0.62 (<0.5-3.2), 11.5 (3.2-43.5) and 0.63 (<0.5-5.46) mg dl(-1) for the same groups. A statistically significant difference was found between HP+ patients and both HP- cases and healthy blood donors for PCT levels, and higher PCT levels were found on admission in cases of bacteraemia than in the other groups (P < 0.05). PCT levels of HP+ cases decreased significantly (from 1.39 to 0.86) between admission and the post-treatment period (30 days); however, PCT levels remained higher than the cut-off value (0.5 ng ml(-1)). Similar ranges of CRP levels were found over the same time-period. The sensitivity of PCT was found to be higher than that of CRP on admission, but the specificity of PCT was found to be lower than that of CRP on the day of admission (65 and 74%, respectively). The sensitivity of PCT was the same as that of CRP for the post-treatment period, but specificity of PCT was higher than that of CRP for the post-treatment period (83 and 76%, respectively). It was concluded that PCT and CRP are not very effective markers for H. pylori infection in primary diagnosis or in eradication follow-up after therapy when used in parallel with conventional diagnostic methods, even if there is a difference in PCT and CRP levels between HP+ and HP- cases on admission.

The effects of IgM-enriched immunoglobulin preparations in patients with severe sepsis [ISRCTN28863830].

INTRODUCTION: In this prospective, randomized controlled study, we aimed to evaluate the effect of IgM-enriched immunoglobulin treatment on progression of organ failure and septic shock in patients with severe sepsis. MATERIALS AND METHODS: Forty-two patients with severe sepsis were enrolled in the study. Patients in the study group (n = 21) received an intravenous immunoglobulin preparation (Pentaglobin in addition to standard therapy. Pentaglobin therapy was commenced on the day of diagnosis of severe sepsis: 5 ml/kg per day Pentaglobin (38 g/l IgG, 6 g/l IgM, and 6 g/l IgA) was infused over 6 hours and repeated for 3 consecutive days. Patients in the control group (n = 18) received standard sepsis therapy, but no immunoglobulin administration. Blood samples for procalcitonin (PCT) measurements were taken daily for 8 days. Severity of critical illness and development of organ failure were assessed by obtaining daily acute physiological and chronic health evaluation (APACHE) II and sequential organ failure assessment (SOFA) scores. RESULTS AND DISCUSSION: Procalcitonin levels showed a statistically significant decrease in the Pentaglobin group (P < 0.001); however, an improvement in SOFA scores could not be demonstrated. Procalcitonin levels and SOFA scores did not change significantly in the control group. Septic shock incidence (38% versus 57%) and 28-day mortality rate (23.8% versus 33.3%) were found to be similar between the Pentaglobin and control groups. The evaluation of serial APACHE II scores did not demonstrate a difference between Pentaglobin and control groups either. CONCLUSION: Present data could not demonstrate any beneficial effects of polyclonal immunoglobulin preparation Pentaglobin on organ morbidity, septic shock incidence and mortality rate in patients with severe sepsis.