Development of the first edition of African treatment guidelines for common bacterial infections and syndromes

Standard treatment guidelines (STGs) are an important tool for ensuring high quality clinical care and prudent antimicrobial use (AMU) and stewardship (AMS). In 2018, African Union (AU) member state representatives recognized the lack of STGs as a barrier to AMS at national and facility levels. Previous research reported that only 17 of 55 (31%) member states had STGs that provided disease- or pathogen-specific antimicrobial treatment recommendations, excluding those that covered only treatment of HIV, malaria, and tuberculosis). The Africa Centres for Disease Control and Prevention convened expert panels to develop first edition antibiotic treatment guidelines for priority infectious diseases and clinical syndromes for pediatric and adult patient populations in Africa. The purpose of the guidelines is to provide healthcare workers with treatment guidance by harmonising existing national STGs, filling gaps where existing STGs are not available, and serving as a model for future guidelines. Two expert panels of 28 total clinicians, pharmacists, and other relevant stakeholders from 14 AU member states representing each continental region convened to develop consensus treatment recommendations for select priority bacterial infections and clinical syndromes. In developing recommendations, the panels considered treatment recommendations from existing STGs, drug availability, clinical experience, and available antimicrobial resistance data. The guidelines underwent an external review process where clinical stakeholders who did not serve on either panel were invited to submit feedback prior to their publication. The guidelines provide empiric antibiotic therapy guidelines – including drug selection, route of administration, formulation, dosage, and therapy duration – and principles of stewardship for 28 bacterial infections or clinical syndromes. The first edition guidelines for the treatment of common infectious diseases and clinical syndromes in Africa aims to improve clinical treatment and antimicrobial stewardship and will serve as a template for future regional guidelines.

Risk factors of methicillin-resistant Staphylococcus aureus bacteremic pneumonia in the emergency department

The infection rate of methicillin-resistant Staphylococcus aureus (MRSA) has increased worldwide and MRSA bacteremic pneumonia is associated with a high mortality rate. This is a retrospective study conducted at a university hospital in Korea involving adult patients diagnosed as bacteremic pneumonia caused by S. aureus in the ED between January 2009 and December 2019. We compared MRSA bacteremic pneumonia patients (n = 56) to methicillin-susceptible S. aureus bacteremic pneumonia patients (n = 49). Our study showed that that underlying hypertension (OR = 5.68; 95% CI = 2.00–16.11; p = 0.001) and cerebrovascular disease (OR = 3.54; 95% CI = 1.06–11.75; p = 0.038), recent intravenous therapy within 1 month (OR = 8.38; 95% CI = 2.88–24.38; p = 0.0001), and pleural effusion on chest radiography (OR = 5.77; 95% CI = 1.79–18.57; p = 0.003) were independent risk factors for MRSA bacteremic pneumonia presenting to the ED. Although MRSA infection has been more frequently derived from the community than before, inappropriate empiric antibiotic treatment was overwhelmingly observed in the majority of patients in our study. Considering the resistance of MRSA to the typical empiric regimen prescribed for community-acquired pneumonia, emergency physicians should pay attention to the predictors for MRSA bacteremic pneumonia including pleural effusion on chest radiography when deciding on the appropriate empiric antimicrobial therapy for pneumonia patients in the ED.

Increased Long-Term Mortality in Patients Admitted to the Intensive Care Unit with Health-Care Associated Pneumonia

The American Thoracic Society (ATS) and the Infectious Diseases Society of America (IDSA) developed and periodically update guidelines for the diagnosis and management of community-acquired and nosocomial pneumonia based on the patient-care setting in which pneumonia evolved. ATS/IDSA provides guidelines for empiric antibiotic choices based on the category of pneumonia that is diagnosed. Pneumonia is a significant cause of mortality in the United States and when combined with influenza ranks as the eighth leading cause of death nationwide yet little is known about the mortality of critically ill patients with pneumonia that require admission to a medical intensive care unit (ICU). Our findings suggest that older age, higher severity of illness at ICU admission, and chronic comorbid illnesses are the main contributors to long-term mortality from pneumonia requiring ICU admission. In this cohort, we found an independent association between increased mortality and admission from the general hospital ward rather than directly from the emergency department. Our study did not demonstrate that initial guideline-based antibiotic therapy was associated with a reduction in short-term mortality; however, it did demonstrate a high prevalence of resistant pathogens in HCAP/HAP patients, which reflects ATS/IDSA guideline expectations

SEPSIS MARKERS AND SENSITIVITY OF STAPHYLOCOCCUS AUREUS AND ESCHERICHIA COLI ISOLATES IN A GENERAL HOSPITAL SETTING

Представлены результаты проспективного обследования 80 больных ГКБ №7 с бактериемией с октября 2019 года по февраль 2021 года из различных отделений госпиталя. Производилась оценки показателей маркеров сепсиса - пресепсина, прокальцитонина и С-реактивного белка (СРБ) в крови больных в динамике эмпирической терапии антимикробными препаратами (АМП). Наибольшее число больных с выявленной бактериемией находилось в отделении ОАРИТ - 39 пациентов, у 25 из них был диагностирован сепсис по шкале СЕПСИС III, вызванный известными патогенами Staphylococcus aureus (46,6%) и Escherichia coli (36,6%). Для эмпирического лечения применялись различные антибиотики: ампенициллин, амикацин, меропенем, цефотаксим, метрид, ципрофлоксацин, ципрокс, цефлокс, цефазолин, цефтриаксон, левофлоксацин. Уровни прокальцитонина составляют для больных с клиническими изолятами E. coli 20,8±3,1нг/мл, а для изолятов St. aureus 15,7±1,8 нг/мл. После терапии АМП наблюдается значительное снижение показателей до 1,43±0,6 и 2,3±0,9 нг/мл., что позволяет признать эффективность эмпирической антибиотикотерапии при инфекциях кровотока. Высокая чувствительность клинических изолятов Escherichia coli отмечена к препаратам группы карбапенемов - имипенему и меропенему (90,9%), низкая к эртапенему (72,7%). 100% чувствительность все изоляты показали по отношению к АМП из группы глицилциклинов - тигециклину, который структурно сходен с тетрациклинами. Высокой резистеностью клинические изоляты Staphylococcus aureus обладают к пенициллину (92,9%), липопептиду природного происхождения даптомицину (85,8%) и препарату из группы линкозамидов - клиндамицину (64,3%). The results of a prospective examination of 80 patients with bacteremia from October 2019 to February 2021 from various departments of the hospital are presented. The largest number of patients with detected bacteremia were in the OARIT department - 39 patients, 25 of them were diagnosed with sepsis according to the SEPSIS III scale, caused by known pathogens Staphylococcus aureus (46.6%) and Escherichia coli (36.6%). For empirical treatment, various antibiotics were used: ampenicillin, amikacin, meropenem, cefotaxime, metrid, ciprofloxacin, ciprox, ceflox, cefazolin, ceftriaxone, levofloxacin. Procalcitonin levels for patients with clinical E. coli isolates are 20.8 ± 3.1 ng / ml, and for St. aureus 15.7 ± 1.8 ng / ml. After AMP therapy, there is a significant decrease in indicators to 1.43 ± 0.6 and 2.3 ± 0.9 ng / ml, which makes it possible to recognize the effectiveness of empiric antibiotic therapy for bloodstream infections. High sensitivity of clinical isolates of Escherichia coli was noted to drugs of the carbapenem group - imipenem and meropenem (90.9%), low to ertapenem (72.7%). All isolates showed 100% sensitivity to AMPs from the glycylcycline group - tigecycline, which is structurally similar to tetracyclines. Clinical isolates of Staphylococcus aureus are highly resistant to penicillin (92.9%), natural lipopeptide daptomycin (85.8%), and a drug from the lincosamide group - clindamycin (64.3%).

Is There a Difference in Clinical Features, Microbiological Epidemiology and Effective Empiric Antimicrobial Therapy Comparing Healthcare-Associated and Community-Acquired Vertebral Osteomyelitis?

Background: Empiric antibiotic therapy for suspected vertebral osteomyelitis (VO) should be initiated immediately in severely ill patients, and might be necessary for culture-negative VO. The current study aimed to identify differences between community-acquired (CA) and healthcare-associated (HA) VO in terms of clinical presentation, causative pathogens, and antibiotic susceptibility. Methods: Cases of adult patients with VO treated at a German university orthopaedic trauma center between 2000 and 2020 were retrospectively reviewed. Patient history was used to distinguish between CA and HA VO. Susceptibility of antibiotic regimens was assessed based on antibiograms of the isolated pathogens. Results: A total of 155 patients (with a male to female ratio of 1.3; and a mean age of 66.1 ± 12.4 years) with VO were identified. In 74 (47.7%) patients, infections were deemed healthcare-associated. The most frequently identified pathogens were Staphylococcus aureus (HAVO: 51.2%; CAVO: 46.8%), and Coagulase-negative Staphylococci (CoNS, HAVO: 31.7%; CAVO: 21.3%). Antibiograms of 45 patients (HAVO: n = 22; CAVO: n = 23) were evaluated. Significantly more methicillin-resistant isolates, mainly CoNS, were found in the HAVO cohort (27.3%). The highest rate of resistance was found for cefazolin (HAVO: 45.5%; CAVO: 26.1%). Significantly higher rates of resistances were seen in the HAVO cohort for mono-therapies with meropenem (36.4%), piperacillin–tazobactam (31.8%), ceftriaxone (27.3%), and co-amoxiclav (31.8%). The broadest antimicrobial coverage was achieved with either a combination of piperacillin–tazobactam + vancomycin (CAVO: 100.0%; HAVO: 90.9%) or meropenem + vancomycin (CAVO: 100.0%; HAVO: 95.5%). Conclusion: Healthcare association is common in VO. The susceptibility pattern of underlying pathogens differs from CAVO. When choosing an empiric antibiotic, combination therapy must be considered.

Antibiotic Stewardship in Patients after Cellular Therapy with Febrile Neutropenia- a Single Center Prospective Unblinded Randomized Trial

Background: Neutropenic fever is a life-threatening condition which is common in patients undergoing allogeneic/autologous hematopoietic cell transplantation (HCT) or chimeric antigen receptor - T cell (CAR-T) therapy. Empirical treatment includes monotherapy with a beta-lactam containing anti-pseudomonal activity. Nevertheless, stewardship of antibiotic in this vulnerable population is controversial. Methods: This was a single center, prospective, unblinded randomized study, of patients after HCT or CAR-T therapy that were enrolled between January 2020 and March 2021. Allocation was concealed in sequentially numbered sealed opaque envelopes. All patients signed informed consent and the study was approved by the Tel Aviv Medical Center Institutional Review Board. Patients were randomly assigned to receive either standard empiric antibiotic ( piperacillin/tazobactam or ceftazidime) that was continued until recovery of counts (control group), or standard empiric antibiotic that was discontinued after 48-72 hours providing there was no evidence of clinical or microbiology documented infection (intervention group). Rapid identification of bloodstream infections was performed with BioFire filmarray multiplex PCR assay (bioMerieux), and results were used to adjust antibiotic treatment early. The primary outcome was the percentage of days without empiric antibiotic (antibiotic-free-neutropenia days). Secondary outcome included successful response to treatment, defined as the combination of- continuation of clinical improvement on day 5 after initiation of antibiotic, no reoccurrence of bacetermia/fever/clinical infection signs on day 5, and no need for additional therapy on day 4-5 after starting antibiotic. Breakthrough fever, death within 30 days of episode onset, duration of hospitalization, duration of neutropenia, graft vs. host disease (GVHD) and characteristics of cytokine release syndrome (CRS) were also evaluated, as appropriate. Results: 110 patients were randomized to standard therapy (control group, n=51) and antibiotic stewardship strategy (intervention group, n=59), Figure 1. The patients' baseline characteristics were well-balanced between the 2 groups, Table 1. Febrile neutropenia occurred in 91 of the patients, and these patients were eligible for the per-protocol analysis. In the intention-to-treat population, the fraction of antibiotic-free neutropenia days was significantly higher for patients allocated to the stewardship arm, compared to those allocated to the standard arm (median [IQR], 0.8 [0.62-0.86] versus 0.51 [0.17-0.86], respectively, p=.0016). This was also true for the subgroups of patients treated per-protocol (median [IQR], 0.75 [0.61-0.83] versus 0.42 [0.12-0.72], respectively, p<.001) and in the subgroups of patients after allogeneic HCT, autologous HCT and CAR-T therapy (0.75 [0.57-0.86] vs. 0.5 [0.40-0.51], p=.0046; 0.66 [0.62-0.83] vs. 0.59 [0.19-0.81], p=.077; and 0.7 [0.45-0.82] vs 0.06 [0-0.28], p=.025, respectively), Figure 2. There was no difference in the success rate between the 2 groups (84.7% vs. 78%, P =0.45). Thirty-day death rate was similarly low in both groups. Other outcome are depicted in Table 2. Linear regression was used to assess the interaction of patient and treatment variables with the fraction of antibiotic-free days. Assignment to the stewardship arm was significantly associated with a higher fraction of antibiotic-free days (p=.003), whereas CART treatment was associated with a lower fraction of antibiotic-free days (p=.004). Conclusions: This is the first randomized study showing in a homogenous population of patients after cellular therapy, the safety of antibiotic stewardship. Optimization of antibiotic schedule is a widely available and cost-effective strategy to improve treatment outcomes in patients with high risk febrile neutropenia after cellular therapy. Figure 1 Figure 1. Disclosures Ram: Gilead: Honoraria; Novartis: Honoraria. Avivi: Kite, a Gilead Company: Speakers Bureau; Novartis: Speakers Bureau.