Outcomes of long-acting injectable antipsychotics use in pregnancy: A literature review.

BACKGROUND: Women with a history of serious psychotic disorders are at increased risk of disease relapse during pregnancy. Long-acting injectable (LAI) antipsychotics have been widely used to improve adherence and prevent relapse in patients with various severe psychotic disorders, but there is a lack of high-quality data from previous research on the safety of LAI antipsychotics during pregnancy. AIM: To summarize relevant data on maternal, pregnancy, neonatal, and developmental outcomes from published cases of LAI antipsychotic use in pregnancy. METHODS: A literature search was performed through November 11, 2023, using three online databases: PubMed/MEDLINE, Scopus, and Web of Science. Case reports or case series that reported information about the outcomes of pregnancy in women who used LAI antipsychotics at any point in pregnancy, with available full texts, were included. Descriptive statistics, narrative summation, and tabulation of the extracted data were performed. RESULTS: A total of 19 publications satisfied the inclusion criteria: 3 case series, 15 case reports, and 1 conference abstract. They reported the outcomes of LAI antipsychotic use in 74 women and 77 pregnancies. The use of second-generation LAI antipsychotics was reported in the majority (n = 47; 61.0%) of pregnancies. First-generation LAI antipsychotics were administered during 30 pregnancies (39.0%). Most of the women (approximately 64%) had either satisfactory control of symptoms or no information about relapse, while approximately 12% of them had developed gestational diabetes mellitus. A minority of cases reported adverse outcomes such as stillbirth, spontaneous abortion, preterm birth, low birth weight, congenital anomalies, and neurological manifestations in newborns. However, there were no reports of negative long-term developmental outcomes. CONCLUSION: Currently available data seem reassuring, but further well-designed studies are required to properly evaluate the risks and benefits of LAI antipsychotic use during pregnancy.

Factors affecting outcome in hospitalized patients treated according to recommendations from clinical pharmacologists.

OBJECTIVE: Although some of the positive effects of consulting a clinical pharmacologist when using complex treatment schedules have been demonstrated, the factors determining treatment outcomes are largely unknown. A main aim of this study was to identify and analyze the factors associated with the treatment outcomes in hospital patients in whom a therapeutic plan proposed by a clinical pharmacologist had been accepted and implemented. MATERIALS AND METHODS: The research was conducted as a retrospective cohort study on a random sample of 200 inpatients in the University Clinical Center Kragujevac, Serbia. The main outcome variables were i) in-hospital mortality, ii) inadequate clinical response to the therapy or pharmacological recommendations proposed by a clinical pharmacologist, iii) the total length of hospitalization, and iv) the length of hospitalization after consulting a clinical pharmacologist. The effect of putative predictors and confounders on the study outcomes were analyzed using multivariate regression models. RESULTS: Early integration of clinical pharmacologists in the course of patient treatment was associated with a reduction in the risk of a fatal outcome (OR = 1.146; 95% CI, 1.006 - 1.305; p = 0.040). Delay in consulting a clinical pharmacologist was associated with a longer overall length of patient hospitalization (B = 1.592; 95% CI, 1.100 - 2.084; p = 0.000). When the reasons for consulting a clinical pharmacologist involved the choice of drug or the occurrence of adverse drug reactions, the duration of hospitalization following the consultation was shorter by ~ 4 days (B = -4.337; 95% CI, -8.190 to -0.484; p = 0.028) and 12 days (B = -12.024; 95% CI, -19.108 to -4.940; p = 0.001), respectively. CONCLUSION: To achieve more favorable treatment outcomes in the case of difficult-to-treat hospital inpatients, clinical pharmacologists should be consulted early in the course of the disease, especially when the choice of drug is difficult, and the occurrence of adverse drug reactions is an important issue.

Kounis Syndrome Associated With the Use of Diclofenac.

BACKGROUND: Diclofenac is a widely used analgesic, anti-inflammatory, antipyretic drug. In several case reports, its use was associated with the occurrence of Kounis syndrome. The aim of this review was to investigate and summarize published cases of Kounis syndrome suspected to be associated with the use of diclofenac. METHODS: Electronic searches were conducted in PubMed/MEDLINE, Scopus, Web of Science, Google Scholar, and the Serbian Citation Index. RESULTS: Twenty publications describing the 20 patients who met inclusion criteria were included in the systematic review. Specified patient ages ranged from 34 to 81 years. Eighteen (90.0%) patients were male. Five patients (25.0%) reported a previous reaction to diclofenac. Reported time from the used dose of diclofenac to onset of the first reaction symptoms ranged from immediately to 5 hours. Diclofenac caused both type I and type II Kounis syndrome, with the presence of various cardiovascular, gastrointestinal, dermatologic, and respiratory signs and symptoms. Most patients experienced hypotension (n = 15 [75.0%]) and chest pain (n = 12 [60.0%]). The most frequently reported finding on electrocardiogram was ST-segment elevations (n = 17 [85.0%]). Coronary angiogram showed normal coronary vessels in 9 patients (45.0%), with some pathologic findings in 8 patients (40.0%). CONCLUSION: Clinicians should be aware that Kounis syndrome may be an adverse effect of diclofenac. Prompt recognition and withdrawal of the drug, with treatment of both allergic and cardiac symptoms simultaneously, is important.

Epidemiology and risk factors for healthcare-associated infections caused by Pseudomonas aeruginosa.

Pseudomonas aeruginosa (PA) is a globally recognized cause of healthcare-associated infections (HAIs). The aim of our cross-sectional study, conducted in a Serbian tertiary care hospital, was to investigate clinical characteristics of HAIs caused by the PA, the prevalence of various drug-resistant phenotypes of this pathogen, and risk factors for their occurrence. Prolonged ICU stay and previous carbapenem administration were independent risk factors for HAIs caused by carbapenem-resistant PA, while HAIs caused by multidrug-resistant PA were more frequent in patients with prolonged stay in an ICU, who were previously hospitalized at another department and previously treated with aminoglycosides, fluoroquinolones or glycopeptides. The prolonged ICU stay was the only significant risk factor for HAIs caused by extensively drug-resistant PA. To decrease the incidence of HAIs caused by drug-resistant PA, a multifaceted approach is necessary, including staff education, antibiotic stewardship, improving hygiene, shortening hospitalization, and minimizing exposure to invasive medical procedures/devices.

Correlation between cefepime utilisation and Pseudomonas aeruginosa resistance rates to ß-lactams and carbapenems in patients with healthcare-associated infections.

OBJECTIVES: There is direct link between overutilisation or abuse of antibiotics and Pseudomonas aeruginosa resistance rates, but other factors may also influence the resistance rate. This study aimed to observe changes in P. aeruginosa resistance rates in patients with hospital-acquired infections (HAIs) following a period of cefepime unavailability in an ICU. METHODS: The study was designed as a retrospective observational analysis of trends in antibiotic utilisation and density of antibiotic resistance. It covered only P. aeruginosa isolates causing HAIs obtained from patients aged >18years. Isolates taken <48h after admission to the ICU and duplicate isolates were excluded. The effects of cefepime withdrawal from prescribing during the 2-year period on P. aeruginosa resistance density trends were also followed. RESULTS: During the study period (2009-2016), a total of 318 non-duplicate P. aeruginosa isolates causing HAIs in the ICU were collected. The predominant anatomical localisation of these infections (nearly 95%) was the lungs (pneumonia), surgical sites and urinary tract (69.18%, 18.24% and 6.92%, respectively). The isolates showed a lower resistance density (per/1000 PDs) in the last year (2016) compared with the first year of observation (2009) for all monitored antibiotics, with a peak in 2011. Although a decreasing trend of resistance density was recorded for all examined drugs, statistical significance was noted only for imipenem, meropenem and piperacillin/tazobactam (P<0.05) CONCLUSIONS: Temporary withdrawal of cefepime in a hospital resulted in a significant decrease in the density of P. aeruginosa isolates resistant to imipenem, meropenem, piperacillin/tazobactam, ceftazidime and cefepime.

Previous Antibiotic Exposure and Antimicrobial Resistance Patterns of Acinetobacter spp. and Pseudomonas aeruginosa Isolated from Patients with Nosocomial Infections.

BACKGROUND: The alarming spread of antibiotic-resistant bacteria causing healthcare-associated infections has been extensively reported in recent medical literature. AIMS: To compare trends in antimicrobial consumption and development of resistance among isolates of Acinetobacter spp. and Pseudomonas aeruginosa that cause hospital infections. STUDY DESIGN: Cross-sectional study. METHODS: A study was conducted in a tertiary healthcare institution in central Serbia, during the 7-year period between January 2009 and December 2015. The incidence rate of infections caused by Acinetobacter or Pseudomonas, as well as their resistance density to commonly used antibiotics, were calculated. Utilization of antibiotics was expressed as the number of defined daily doses per 1000 patient-days. RESULTS: A statistically significant increase in resistance density in 2015 compared to the first year of observation was noted for Acinetobacter, but not for Pseudomonas, to third-generation cephalosporins (p=0.008), aminoglycosides (p=0.005), carbapenems (p=0.003), piperacillin/tazobactam (p=0.025), ampicillin/sulbactam (p=0.009) and tigecycline (p=0.048). CONCLUSION: Our study showed that there is an association between the resistance density of Acinetobacter spp. and utilization of carbapenems, tigecycline and aminoglycosides. A multifaceted intervention is needed to decrease the incidence rate of Acinetobacter and Pseudomonas hospital infections, as well as their resistance density to available antibiotics.

Distribution and antibiotic susceptibility of pathogens isolated from adults with hospital-acquired and ventilator-associated pneumonia in intensive care unit.

Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are the most common hospital infections with the highest prevalence in intensive care units (ICU). The aim of this study was to investigate prevalence of bacterial pathogens isolated from ICU patients with HAP/VAP and reveal their susceptibility rates in order to establish a basis for empirical antibiotic therapy. Prospective cohort study was conducted in central ICU of Clinical Centre Kragujevac, Serbia, from January 2009 to December 2015, enrolling 620 patients with documented HAP (38.2%) or VAP (61.8%). Gram-negative agents were isolated in 95.2%. Generally, the most common pathogens were Acinetobacter spp. and Pseudomonas aeruginosa, accounting for over 60% of isolates. The isolates of Acinetobacter spp. in HAP and VAP had low susceptibility to the 3rd generation cephalosporins, aminoglycosides, fluoroquinolones (0-10%). The rate of susceptibility to piperacillin-tazobactam was below 15%, whereas for carbapenems and 4th generation cephalosporins it was about 15-20%. Isolates of P. aeruginosa from HAP and VAP showed low susceptibility to ciprofloxacin and gentamicin (below 10%), followed by amikacin (25%), while the rate of susceptibility to carbapenems and 4th generation cephalosporin was 30-35%. Furthermore, 86% of isolates of P. aeruginosa non-susceptible to carbapenems were also non-susceptible to ciprofloxacin. The highest level of susceptibility from both groups was retained toward piperacilin-tazobactam. In ICU within our settings, with predominance and high resistance rates of Gram-negative pathogens, patients with HAP or VAP should be initially treated with combination of carbapenem or piperacillin-tazobactam with an anti-pseudomonal fluoroquinolone or aminoglycoside. Colistin should be used instead if Acinetobacter spp. is suspected. Vancomycin, teicoplanin or linezolide should be added only in patients with risk factors for MRSA infections.

Risk factors for hospital infections caused by carbapanem-resistant Acinetobacter baumannii.

INTRODUCTION: Acinetobacter baumannii is one of major causative agents of severe, life-threatening hospital infections (HIs), especially in intensive care units (ICUs). Our aim was to discover the risk factors associated with the emergence of HIs caused by carbapenem-resistant Acinetobacter baumannii (CRAB), as well as those associated with death in patients who suffer from such infections. METHODOLOGY: A prospective cohort study was conducted over a five-year period in the medical-surgical ICU of the Clinical Centre in Kragujevac, Serbia. The study group comprised patients who had HIs caused by CRAB, while the control group comprised patients infected with carbapenem-sensitive Acinetobacter baumannii. RESULTS: In total, 137 patients developed HIs caused by Acinetobacter baumannii. The mean age of the patients was 59.65 ± 16.08 years, and 99 (72.26%) of them were males. In 95 patients (69.35%), the infection was caused by CRAB. There were six independent risk factors for CRAB infections: use of mechanical ventilation, previous stay in another department, stay in ICU for more than a month, and previous use of carbapenems, aminoglycosides, and metronidazole. Three independent risk factors were found for death in patients with HIs caused by CRAB: use of mechanical ventilation, previous stay in another department, and previous use of carbapenems. CONCLUSIONS: The results of this study can be helpful when identifying patients with risk of HIs caused by CRAB and in planning preventive measures. Modification of known risk factors and appropriate institutional policy of antibiotic utilization are important measures that may decrease the incidence and mortality of such infections.

Risk factors for healthcare-acquired urinary tract infections caused by multi-drug resistant microorganisms.

Introduction: Healthcare-acquired urinary tract infections (HAUTI) make up to 40% of all healthcareacquired infections and contribute significantly to hospital morbidity, mortality, and overall cost of treatment. Objective: The aim of our study was to investigate possible risk factors for development of HAUTI caused by multi-drug resistant pathogens. Methods: The prospective case-control study in a large tertiary-care hospital was conducted during a five-year period. The cases were patients with HAUTI caused by multi-drug resistant (MDR) pathogens, and the controls were patients with HAUTI caused by non-MDR pathogens. Results: There were 562 (62.6%) patients with MDR isolates and 336 (37.4%) patients with non-MDR isolates in the study. There were four significant predictors of HAUTI caused by MDR pathogens: hospitalization before insertion of urinary catheter for more than eight days (ORadjusted = 2.763; 95% CI = 1.352­5.647; p = 0.005), hospitalization for more than 15 days (ORadjusted = 2.144; 95% CI = 1.547­2.970; p < 0.001), previous stay in another department (intensive care units, other wards or hospitals) (ORadjusted = 2.147; 95% CI = 1.585­2.908; p < 0.001), and cancer of various localizations (ORadjusted = 2.313; 95% CI = 1.255­4.262; p = 0.007). Conclusion: Early removal of urinary catheter and reduction of time spent in a hospital or in an ICU could contribute to a decrease in the rate of HAUTI caused by MDR pathogens.

Health care-acquired infections in neonatal intensive care units: risk factors and etiology.

A 1-year prospective cohort study of health care-acquired infections was conducted at the neonatal intensive care unit of the University Clinical Centre Kragujevac, Serbia. The incidence rate of neonates with health care-acquired infections was 18.6%, and the incidence rate of the infections themselves was 19.4%. The incidence density of the health care-acquired infections was 9.1 per 1,000 patient days. The independent risk factors for health care-acquired infections were birth weight, length of hospitalization, duration of mechanical ventilation, and Apgar score. More than half of all isolated microorganisms were Klebsiella-Enterobacter (39.3%) and Escherichia coli (25.0%).

Nosocomial urinary tract infections caused by Pseudomonas aeruginosa and Acinetobacter species: sensitivity to antibiotics and risk factors.

BACKGROUND: Pseudomonas aeruginosa and Acinetobacter species frequently cause intrahospital urinary tract infections (IUTI), contributing to increased hospital morbidity and mortality. Our objective was further exploration of possible risk factors for development of IUTI caused by P aeruginosa and Acinetobacter spp, including their resistance to various antibiotics. METHODS: The prospective case control study was conducted in Clinical Center Kragujevac, Serbia, during the period January 2009 to December 2011 and covered all patients with IUTI according to the Centers for Disease Control and Prevention criteria. The patients classified as "cases" had an IUTI caused by P aeruginosa or Acinetobacter spp. The control patients were matched to the cases and selected randomly from the remaining patients. RESULTS: There were 79 cases (11.9%) and 586 (88.1%) controls in the study. According to the multivariate binary logistic regression, there were 3 significant predictors of P aeruginosa and Acinetobacter spp IUTI: male sex (odds ratio [OR], 0.423; 95% confidence interval [CI]: 0.251-0.711; P = .001), stay in another hospital ward before emergence of IUTI (OR, 1.704; 95% CI: 1.013-2.864; P = .044), and previous use of penicillins and their combinations with inhibitors of ß-lactamases (OR, 2.643; 95% CI: 1.044-6.692; P = .040). CONCLUSION: Knowing that IUTI caused by above-mentioned bacteria are especially frequent among male patients, after previous use of penicillins, and in patients who spent some time previously at other wards, sound strategies for prevention of such infections in clinical practice should be developed.

Effects of methyldopa and nifedipine on uteroplacental and fetal hemodynamics in gestational hypertension.

OBJECTIVE: Investigation of methyldopa and nifedipine effects on maternal and fetal hemodynamics in women with mild gestational hypertension during the third pregnancy trimester. METHODS: A prospective cohort study. Methyldopa effects were followed in 28 patients, and nifedipine effects in another 28 patients. There were also 28 healthy controls. RESULTS: Uterine artery blood velocity waveform indices were improved only by nifedipine. Neither of the drugs affected the indices in umbilical and fetal middle cerebral artery. Both drugs normalized maternal blood pressure and pulse. CONCLUSIONS: Methyldopa and nifedipine did not show clinically significant influence on umbilical artery and fetal cerebral blood flow.