Evaluation of antibiotic use in Pediatric Intensive Care Unit of a developing country

Background:Pediatric Intensive Care Unit (PICU) patients are often prescribed antibiotics with a low threshold in comparison to patients elsewhere. Irrational antibiotics use can lead to rapid emergence of drug resistance, so surveillance of their use is important.Objectives:To evaluate the use of antibiotics in relation to bacteriological findings in PICU of a Tertiary Hospital.Methods:Retrospective review of medical records of all children (age 1 month–16 years) admitted in our closed multidisciplinary-cardiothoracic PICU from January to June 2013 was performed, after approval from Ethical Review Committee. For each antibiotic, indication (prophylactic, empiric, therapeutic) and duration of use were recorded. All diagnoses of infections were recorded according to diagnostic criteria of IPSCC 2005. Results are presented as frequency and percentages and median with inter quartile range using SPSS version 19.Results:All of the total 240 patients admitted in PICU during the study period received antibiotics: 43% (n = 104) prophylactically, 42% (n = 102) empirically, and 15% (n = 15) therapeutically. Median number of antibiotic use per patient in PICU was 3, with range of 1–7. 25% received 1 antibiotic, 23% received 2 antibiotics, 29% received 3 antibiotics, and rest received ≥4 antibiotics. Most commonly used antibiotics were cefazolin, meropenem, vancomycin and ceftriaxone, and most frequently used combination was meropenem and vancomycin. In majority of the cases, (70%) empiric antibiotic combinations were stopped in 72 h.Conclusion:This is the first report of antibiotics use in PICU from our country, which shows that antibiotics are prescribed universally in our PICU. Strategies to assess the need for antibiotic use are needed.     

When not to start antibiotics: avoiding antibiotic overuse in the intensive care unit

BackgroundMost intensive care unit (ICU) patients receive broad-spectrum antibiotics. While lifesaving in some, in others these treatments may be unnecessary and place patients at risk of antibiotic-associated harms.ObjectivesTo review the literature exploring how we diagnose infection in patients in the ICU and address the safety and utility of a ‘watchful waiting’ approach to antibiotic initiation with selected patients in the ICU.SourcesA semi-structured search of PubMed and Cochrane Library databases for articles published in English during the past 15 years was conducted.ContentDistinguishing infection from non-infectious mimics in ICU patients is uniquely challenging. At present, we do not have access to a rapid point-of-care test that reliably differentiates between individuals who need antibiotics and those who do not. A small number of studies have attempted to compare early aggressive versus conservative antimicrobial strategies in the ICU. However, this body of literature is small and not robust enough to guide practice.ImplicationsThis issue will not likely be resolved until there are diagnostic tests that rapidly and reliably identify the presence or absence of infection in the ICU population. In the meantime, prospective trials that identify clinical situations wherein it is safe to delay or withhold antibiotic initiation in the ICU until the presence of an infection is proven are warranted.     

Childhood urinary tract infection in primary care: a prospective observational study of prevalence,diagnosis, treatment,and recovery

BackgroundThe prevalence of targeted and serendipitous treatment for, and associated recovery from, urinary tract infection (UTI) in pre-school children is unknown.AimTo determine the frequency and suspicion of UTI in children who are acutely ill, along with details of antibiotic prescribing, its appropriateness, and whether that appropriateness impacted on symptom improvement and recovery.MethodSystematic urine sampling from children aged <5years presenting in primary care with acute illness with culture in NHS laboratories.ResultsOf 6079 children’s urine samples, 339 (5.6%) met laboratory criteria for UTI and 162 (47.9%) were prescribed antibiotics at the initial consultation. In total, 576/7101 (8.1%) children were suspected of having a UTI prior to urine sampling, including 107 of the 338 with a UTI (clinician sensitivity 31.7%). Children with a laboratory-diagnosed UTI were more likely to be prescribed antibiotics when UTI was clinically suspected than when it was not (86.0% versus 30.3%, P<0.001). Of 231 children with unsuspected UTI, 70 (30.3%) received serendipitous antibiotics (that is, antibiotics prescribed for a different reason). Overall, 176 (52.1%) children with confirmed UTI did not receive any initial antibiotic. Organism sensitivity to the prescribed antibiotic was higher when UTI was suspected than when treated serendipitously (77.1% versus 26.0%; P<0.001). Children with UTI prescribed appropriate antibiotics at the initial consultation improved a little sooner than those with a UTI who were not prescribed appropriate antibiotics initially (3.5 days versus 4.0 days; P = 0.005).ConclusionOver half of children with UTI on culture were not prescribed antibiotics at first presentation. Serendipitous UTI treatment was relatively common, but often inappropriate to the organism’s sensitivity. Methods for improved targeting of antibiotic treatment in children who are acutely unwell are urgently needed.     

Antibiotic prescribing in patients with COVID-19: rapid review and meta-analysis

BackgroundThe proportion of patients infected with SARS-CoV-2 that are prescribed antibiotics is uncertain, and may contribute to patient harm and global antibiotic resistance.ObjectiveThe aim was to estimate the prevalence and associated factors of antibiotic prescribing in patients with COVID-19.Data SourcesWe searched MEDLINE, OVID Epub and EMBASE for published literature on human subjects in English up to June 9 2020.Study Eligibility CriteriaWe included randomized controlled trials; cohort studies; case series with ≥10 patients; and experimental or observational design that evaluated antibiotic prescribing.ParticipantsThe study participants were patients with laboratory-confirmed SARS-CoV-2 infection, across all healthcare settings (hospital and community) and age groups (paediatric and adult).MethodsThe main outcome of interest was proportion of COVID-19 patients prescribed an antibiotic, stratified by geographical region, severity of illness and age. We pooled proportion data using random effects meta-analysis.ResultsWe screened 7469 studies, from which 154 were included in the final analysis. Antibiotic data were available from 30 623 patients. The prevalence of antibiotic prescribing was 74.6% (95% CI 68.3–80.0%). On univariable meta-regression, antibiotic prescribing was lower in children (prescribing prevalence odds ratio (OR) 0.10, 95% CI 0.03–0.33) compared with adults. Antibiotic prescribing was higher with increasing patient age (OR 1.45 per 10 year increase, 95% CI 1.18–1.77) and higher with increasing proportion of patients requiring mechanical ventilation (OR 1.33 per 10% increase, 95% CI 1.15–1.54). Estimated bacterial co-infection was 8.6% (95% CI 4.7–15.2%) from 31 studies.ConclusionsThree-quarters of patients with COVID-19 receive antibiotics, prescribing is significantly higher than the estimated prevalence of bacterial co-infection. Unnecessary antibiotic use is likely to be high in patients with COVID-19.     

Antibiotic resistance rates and penicillin MIC distribution in patients with streptococcal pneumonia between 2013-2019, and use of antibiotics in clinical practice

PurposeThe purpose of the present study is to investigate the antibiotic resistance rates and use of antibiotics in patients with streptococcal pneumonia in a reference tertiary care hospital for pulmonary diseases in Izmir, Turkey.MethodsA total of 1224 cases with streptococcal pneumonia between 2013 and 2019 were included in the study, retrospectively. Drug susceptibility testing for penicillin and other antibiotics were performed according to the recommendations of EUCAST criteria. Clinical data and general characteristics were collected and evaluated for each patient in accordance with the susceptibility testing report.ResultsTotally, resistance rates for trimethophrim-sulfamethoxazole, penicillin (oxacillin), erythromycin, tetracycline, clindamycin and levofloxacin resistance were 63.5%, 39.8%, 37.7%, 37.6%, 28.8%, and 4.8%, respectively. Antibiotic resistance was not detected against vancomycin,teicoplanin and linezolid. Multidrug resistance rate was found to be 27.1%. It was observed that there was a statistically significant decrease in trimethophrim-sulfamethoxazole, penicillin (oxacillin), erythromycin, clindamycin and levofloxacin resistance rates by years (p: 0.000, 0.004, 0.000, 0.001, 0.010, respectively). The penicillin MIC distribution was higher at the range of 0.12–2 ?μg/mL and there was statistical difference among the ranges of MIC values for the representative years (p:0.033). Among the antibiotics investigated, the most commonly used antibiotic was moxifloxacin.ConclusionsTrimethophrim-sulfamethoxazole resistance rate has been found higher than other antibiotics. As penicillin MIC values were at the range of 0.12–2 ?μg/mL frequently, high doses of penicillin treatment might be required in some patients. It is noteworthy that significant decrease in resistance rates in penicillin, erythromycin, clindamycin and tetracycline could be due to the vaccination programme carried out since 2008 in Turkey. As the empiric use of quinolones is high it would be more appropriate to use it according to the susceptibility testing. It is important to determine the regional antimicrobial susceptibility for Streptococcus pneumoniae to select appropriate empirical antimicrobials in the clinical practice.     

Efficacy and safety of discontinuing antibiotic treatment for uncomplicated respiratory tract infections when deemed unnecessary. A multicentre,randomized clinical trial in primary care

ObjectivesTo determine the benefits and harms of discontinuing unnecessary antibiotic therapy for uncomplicated respiratory tract infections (RTI) when antibiotics are considered no longer necessary.MethodsMulticentre, open-label, randomized controlled clinical trial in primary care centres from 2017 to 2020 (ClinicalTrials.gov, NCT02900820). Adults with RTIs—acute rhinosinusitis, sore throat, influenza or acute bronchitis—who had previously taken any dose of antibiotic for less than 3 days, which physicians no longer deemed necessary were recruited. The patients were randomly assigned in a 1:1 ratio to discontinuing antibiotic therapy or the usual strategy of continuing antibiotic treatment. The primary outcome was the duration of severe symptoms (number of days scoring 5 or 6 on a six-item Likert scale). Secondary outcomes included days with symptoms, moderate symptoms (scores of 3 or 4), antibiotics taken, adverse events, patient satisfaction and complications within the first 3 months.ResultsA total of 467 patients were randomized, out of which 409 were considered valid for the analysis. The mean (SD) duration of severe symptoms was 3.0 (1.5) days for the patients assigned to discontinuation and 2.8 (1.3) days for those allocated to the control group (mean difference 0.2 days; 95% CI –0.1 to 0.4 days). Patients randomized to the discontinuation group used fewer antibiotics after the baseline visit (52/207 (25.1%) versus 182/202 (90.1%); p 0.001). Patients assigned to antibiotic continuation presented a relative risk of adverse events of 1.47 (95% CI 0.80–2.71), but the need for further health-care contact in the following 3 months was slightly lower (RR 0.61; 95% CI 0.28–1.37).ConclusionsDiscontinuing antibiotic treatment for uncomplicated RTIs when clinicians consider it unnecessary is safe and notably reduces antibiotic consumption.     

Utility of prior cultures in predicting antibiotic resistance of bloodstream infections due to Gram-negative pathogens: a multicentre observational cohort study

ObjectivesAppropriate empiric antibiotic therapy in patients with bloodstream infections due to Gram-negative pathogens can improve outcomes. We evaluated the utility of prior microbiologic results for guiding empiric treatment in Gram-negative bloodstream infections.MethodsWe conducted a multicentre observational cohort study in two large health systems in Canada and the United States, including 1832 hospitalized patients with Gram-negative bloodstream infection (community, hospital and intensive care unit acquired) from April 2010 to March 2015.ResultsAmong 1832 patients with Gram-negative bloodstream infection, 28% (n = 504) of patients had a documented prior Gram-negative organism from a nonscreening culture within the previous 12 months. A most recent prior Gram-negative organism resistant to a given antibiotic was strongly predictive of the current organism's resistance to the same antibiotic. The overall specificity was 0.92 (95% confidence interval (CI) 0.91–0.93), and positive predictive value was 0.66 (95% CI 0.61–0.70) for predicting antibiotic resistance. Specificities and positive predictive values ranged from 0.77 to 0.98 and 0.43 to 0.78, respectively, across different antibiotics, organisms and patient subgroups. Increasing time between cultures was associated with a decrease in positive predictive value but not specificity. An heuristic based on a prior resistant Gram-negative pathogen could have been applied to one in four patients and in these patients would have changed therapy in one in five.ConclusionsIn patients with a bloodstream infection with a Gram-negative organism, identification of a most recent prior Gram-negative organism resistant to a drug of interest (within the last 12 months) is highly specific for resistance and should preclude use of that antibiotic.     

Short-course aminoglycosides as adjunctive empirical therapy in patients with Gram-negative bloodstream infection,a cohort study

ObjectiveShort-course aminoglycosides as adjunctive empirical therapy to β-lactams in patients with a clinical suspicion of sepsis are used to broaden antibiotic susceptibility coverage and to enhance bacterial killing. We quantified the impact of this approach on 30-day mortality in a subset of sepsis patients with a Gram-negative bloodstream infection.MethodsFrom a prospective cohort study conducted in seven hospitals in the Netherlands between June 2013 and November 2015, we selected all patients with Gram-negative bloodstream infection (GN-BSI). Short-course aminoglycoside therapy was defined as tobramycin, gentamicin or amikacin initiated within a 48-hour time window around blood-culture obtainment, and prescribed for a maximum of 2 days. The outcome of interest was 30-day all-cause mortality. Confounders were selected a priori for adjustment using a propensity score analysis with inverse probability weighting.ResultsA total of 626 individuals with GN-BSI who received β-lactams were included; 156 (24.9%) also received aminoglycosides for a median of 1 day. Patients receiving aminoglycosides more often had septic shock (31/156, 19.9% versus 34/470, 7.2%) and had an eight-fold lower risk of inappropriate treatment (3/156, 1.9% versus 69/470, 14.7%). Thirty-day mortality was 17.3% (27/156) and 13.6% (64/470) for patients receiving and not receiving aminoglycosides, respectively; yielding crude and adjusted odds ratios for 30-day mortality for patients treated with aminoglycosides of 1.33 (95% CI 0.80–2.15) and 1.57 (0.84–2.93), respectively.ConclusionsShort-course adjunctive aminoglycoside treatment as part of empirical therapy with β-lactam antibiotics in patients with GN-BSI did not result in improved outcomes, despite better antibiotic coverage of pathogens.     

Short-course antibiotics for common infections: what do we know and where do we go from here?

BackgroundOver the past 25 years, researchers have performed >120 randomized controlled trials (RCTs) illustrating short courses to be non-inferior to long courses of antibiotics for common bacterial infections.ObjectiveWe sought to determine whether clinical data from RCTs affirm the mantra of ‘shorter is better’ for antibiotic durations in 7 common infections: pneumonia, urinary tract infection, intra-abdominal infection, bacteraemia, skin and soft tissue infection, bone and joint infections, pharyngitis and sinusitis.SourcesPublished RCTs comparing short- versus long-course antibiotic durations were identified through searches of PubMed and clinical guideline documents.ContentShort-course antibiotic durations consistently result in similar treatment success rates as longer antibiotic courses among patients with community-acquired pneumonia, complicated urinary tract infections in women, gram-negative bacteraemia, and skin and soft tissue infections when the diagnosis is confirmed, appropriate antimicrobials are used, and patients show clinical signs of improvement. For patients with osteomyelitis, 6 weeks of antibiotics is adequate for the treatment of osteomyelitis in the absence of implanted foreign bodies and surgical debridement. Whether durations can be further shortened with debridement is unclear, although small studies are promising.ImplicationsWith few exceptions, short courses were non-inferior to long courses; future research should focus on appropriately defining the patient population, ensuring the correct choice and dose of antimicrobials and developing meaningful outcomes relevant for frontline clinicians.     

Investigating the impact of COVID-19 on primary care antibiotic prescribing in North West London across two epidemic waves

ObjectivesWe investigated the impact of COVID-19 and national pandemic response on primary care antibiotic prescribing in London.MethodsIndividual prescribing records between 2015 and 2020 for 2 million residents in north west London were analysed. Prescribing records were linked to SARS-CoV-2 test results. Prescribing volumes, in total, and stratified by patient characteristics, antibiotic class and AWaRe classification, were investigated. Interrupted time series analysis was performed to detect measurable change in the trend of prescribing volume since the national lockdown in March 2020, immediately before the first COVID-19 peak in London.ResultsRecords covering 366 059 patients, 730 001 antibiotic items and 848 201 SARS-CoV-2 tests between January and November 2020 were analysed. Before March 2020, there was a background downward trend (decreasing by 584 items/month) in primary care antibiotic prescribing. This reduction rate accelerated to 3504 items/month from March 2020. This rate of decrease was sustained beyond the initial peak, continuing into winter and the second peak. Despite an overall reduction in prescribing volume, co-amoxiclav, a broad-spectrum “Access” antibiotic, prescribing rose by 70.1% in patients aged 50 and older from February to April. Commonly prescribed antibiotics within 14 days of a positive SARS-CoV-2 test were amoxicillin (863/2474, 34.9%) and doxycycline (678/2474, 27.4%). This aligned with national guidelines on management of community pneumonia of unclear cause. The proportion of “Watch” antibiotics used decreased during the peak in COVID-19.DiscussionA sustained reduction in community antibiotic prescribing has been observed since the first lockdown. Investigation of community-onset infectious diseases and potential unintended consequences of reduced prescribing is urgently needed.     

The effect of preoperative oral antibiotic use on the risk of periprosthetic joint infection after primary knee or hip replacement: a retrospective study with a 1-year follow-up

ObjectivesAntibiotics are used for various reasons before elective joint replacement surgery. The aim of this study was to investigate patients' use of oral antibiotics before joint replacement surgery and how this affects the risk for periprosthetic joint infection (PJI).MethodsPatients having a primary hip or knee replacement in a tertiary care hospital between September 2002 and December 2013 were identified (n = 23 171). Information on oral antibiotic courses purchased 90 days preoperatively and patients' chronic diseases was gathered. Patients with a PJI in a 1-year follow-up period were identified. The association between antibiotic use and PJI was examined using a multivariable logistic regression model and propensity score matching.ResultsOne hundred and fifty-eight (0.68%) cases of PJI were identified. In total, 4106 (18%) joint replacement operations were preceded by at least one course of antibiotics. The incidence of PJI for patients with preoperative use of oral antibiotics was 0.29% (12/4106), whereas for patients without antibiotic use it was 0.77% (146/19 065). A preoperative antibiotic course was associated with a reduced risk for subsequent PJI in the multivariable model (OR 0.40, 95% CI 0.22–0.73). Similar results were found in the propensity score matched material (OR 0.34, 95% CI 0.18–0.65).ConclusionsThe use of oral antibiotics before elective joint replacement surgery is common and has a potential effect on the subsequent risk for PJI. Nevertheless, indiscriminate use of antibiotics before elective joint replacement surgery cannot be recommended, even though treatment of active infections remains an important way to prevent surgical site infections.     

From genotype to antibiotic susceptibility phenotype in the order Enterobacterales: a clinical perspective

ObjectivesPredicting the antibiotic susceptibility phenotype from genomic data is challenging, especially for some specific antibiotics in the order Enterobacterales. Here we aimed to assess the performance of whole genomic sequencing (WGS) for predicting the antibiotic susceptibility in various Enterobacterales species using the detection of antibiotic resistance genes (ARGs), specific mutations and a knowledge-based decision algorithm.MethodsWe sequenced (Illumina MiSeq, 2×250 bp) 187 clinical isolates from species possessing (n = 98) or not (n = 89) an intrinsic AmpC-type cephalosporinase. Phenotypic antibiotic susceptibility was performed by the disc diffusion method. Reads were assembled by A5-miseq and ARGs were identified from the ResFinder database using Diamond. Mutations on GyrA and ParC topoisomerases were studied. Piperacillin, piperacillin-tazobactam, ceftazidime, cefepime, meropenem, amikacin, gentamicin and ciprofloxacin were considered for prediction.ResultsA total of 1496 isolate/antibiotic combinations (187 isolates × 8 antibiotics) were considered. In 230 cases (15.4%), no attempt of prediction was made because it could not be supported by current knowledge. Among the 1266 attempts, 1220 (96.4%) were correct (963 for predicting susceptibility and 257 for predicting resistance), 24 (1.9%) were major errors (MEs) and 22 (1.7%) were very major errors (VMEs). Concordance were similar between non-AmpC and AmpC-producing Enterobacterales (754/784 (96.2%) vs 466/482 (96.7%), chi-square test p 0.15), but more VMEs were observed in non-AmpC producing strains than in those producing an AmpC (19/784 (2.4%) vs 3/466 (0.6%), chi-square test p 0.02). The majority of VMEs were putatively due to the overexpression of chromosomal genes.ConclusionsIn conclusion, the inference of antibiotic susceptibility from genomic data showed good performances for non-AmpC and AmpC-producing Enterobacterales species. However, more knowledge about the mechanisms underlying the derepression of AmpC are needed.