Empiric Antibiotic Strategies Research Articles

Developing an antibiogram for empiric antibiotic prescribing for adult non-spinal orthopaedic infections in a developing world setting

PurposeEmpiric antibiotic strategies in the treatment of fracture-related infections, chronic osteomyelitis, prosthetic joint infection, and septic arthritis should be based on local microbiological antibiograms. This study aims to describe the microbiology and review the antibiogram profiles of bacterial isolates from patients undergoing surgical treatment for non-spinal orthopaedic infections, to identify the most appropriate empiric antibiotic strategy.MethodsA retrospective review was performed of all cases of non-spinal orthopaedic infections treated surgically from 1 January 2018 to 31 December 2018. The National Health Laboratory Service microbiology database was used to identify all intra-operative microbiological specimens obtained from orthopaedic patients, and data were correlated with the orthopaedic surgical database. Cases were divided into fracture-related infections, chronic osteomyelitis, prosthetic joint infection, and septic arthritis. Antibiotic susceptibility data were used to predict the efficacy of different empiric antibiotic regimens.ResultsA total of 107 cases were included in the study; 184 organisms were cultured. Overall, the most common organism cultured was Staphylococcus aureus (25%) followed by Acinetobacter baumannii (9%), Enterococcus faecalis (7%) and Enterobacter cloacae (5%). Across all categories the oral antibiotic combination with the highest effectiveness (81%) would have been a combination of co-trimoxazole, ciprofloxacin and amoxicillin. The most effective intravenous antibiotic combination would have been either piperacillin–tazobactam, amikacin and vancomycin or meropenem and vancomycin; 90% of tested isolates were susceptible to either of these combinations.ConclusionAntibiogram profiles can serve to guide to empiric antibiotic choice in the management of different categories of non-spinal orthopaedic infections.

Incidence, risk factors and clinical outcomes of multidrug-resistant microorganism infections among patients admitted for decompensated cirrhosis: A prospective study.

Bacterial infections remain one of the main complications in cirrhosis and worsen patients' prognosis and quality of life. An increase in multidrug resistant microorganism (MDRM) infections among patients with cirrhosis, together with infection-related mortality rates, have been reported in recent years. Therefore, adaptation of the initial empiric antibiotic approach to different factors, particularly the local epidemiology of MDRM infections, has been recommended. We aim to describe the main features, outcomes and risk factors of MDRM infections in patients with cirrhosis. Prospective registry of all episodes of in-hospital infections occurring among cirrhotic patients admitted within a 2-year period at a single center. Clinical and microbiological data were collected at the time of infection diagnosis, and the in-hospital mortality rate of the infectious episode was registered. A total of 139 infectious episodes were included. The disease-causing microorganism was identified in 90 episodes (65%), of which 31 (22%) were caused by MDRM. The only two factors independently associated with MDRM infections were rectal colonization by MDRM and a nosocomial or healthcare-associated source. The infection-related mortality rate was 18.7%. MDRM infection and a past history of hepatic encephalopathy were independently associated with in-hospital mortality. Almost one fourth of bacterial infections occurring in admitted cirrhotic patients were due to MDRM. Rectal colonization was the most important risk factor for MDRM infections in decompensated cirrhosis. Screening for MDRM rectal colonization in patients admitted for decompensated cirrhosis should be assessed as a tool to improve local empiric antibiotic strategies.

Surgical site infections are independently associated with the development of postoperative acute-on-chronic liver failure in liver cirrhosis.

Acute-on-chronic liver failure (ACLF) is associated with organ failure and high short-term mortality. Bacterial infections and surgery have been reported as major precipitants for ACLF. However, detailed characterization of postoperative infections after elective surgery in patients with liver cirrhosis and their impact on the development of ACLF have not been investigated yet. A total of 235 patients with cirrhosis without ACLF and proven bacterial infections undergoing elective surgery were included. The primary end point was the development of ACLF within 28 days after surgery, and secondary end points were infection development within 28 days and 3-month ACLF-related mortality. Cox regression analysis was used for identification of risk factors associated with ACLF development, infection development, and mortality. A total of 86 patients (37%) developed ACLF within 28 days after surgery. Patients with new postoperative infections had significantly higher rates of associated ACLF episodes within 28 days (51% vs. 24%, p < 0.001) and higher 3-month mortality ( p < 0.05) than patients without postoperative infections. New infections after surgery [HR: 2.43 (1.59-3.71), p < 0.001] and organ/space surgical site infections [HR: 2.46 (1.26-4.80), p = 0.01] in particular were independent risk factors associated with ACLF development 28 days after surgery. Extensive procedures were associated with the development of new postoperative infection episodes within 28 days. Infections treated with initial appropriate empirical antibiotic strategies showed significantly improved survival. This study characterizes and identifies bacterial infections in general and organ/space surgical site infection in particular as precipitating events for the development of ACLF after elective surgery in patients with cirrhosis. Postoperative ACLF combined with infections leads to higher postoperative short-term mortality than each condition separately, especially in extensive procedures. Interdisciplinary care, early identification of postoperative ACLF and infections, and adequate, broad, and early treatment strategies are needed to improve postoperative outcome.

Empirical antibiotic strategies for acute respiratory infections in children

呼吸系统感染是儿童最常见的感染性疾病，临床医生对病原谱和抗感染策略的掌握是诊治该类疾病的关键，难点在于经验性判断是否存在细菌感染及针对可能菌种选择有效药物。本文将结合儿童呼吸系统感染部位及其常见病原体，参考相关指南，对规范选用抗菌药物提出建议。.

185. Trends in Clinical Presentation and Antibiotic Resistance of Viridans Group Streptococci Bloodstream Infections in Immunocompromised Children

BackgroundLevofloxacin prophylaxis (LVXp) is recommended in children with severe neutropenia from underlying malignancy or hematopoietic cell transplantation (HCT). The impact of LVXp on the epidemiology of viridans group streptococcus bloodstream infections (VGS-BSI) is unknown. At our center, LVXp was prescribed to high-risk children with expected prolonged neutropenia (ANC < 100, > 7 days) as part of a clinical trial (2013-17) and routinely since November 2018. We aim to describe our local epidemiology, antibiotic susceptibilities, and clinical outcomes of VGS-BSI over time.MethodsVGS-BSI from 1/1/10-1/31/21 were identified via the laboratory database. Clinical data of patients followed at NCH with underlying malignancy, severe neutropenia, or HCT were extracted from the electronic health record. Available VGS isolates were subcultured, species identification confirmed by MALDI-ToF or 16s rDNA sequencing and susceptibility to penicillin (PCN), cefepime (CEF), vancomycin (VAN), and LVX performed via Etest per CLSI M100 guidelines. Non-parametric descriptive statistics were applied.ResultsOver a 10-yr period, 111 VGS-BSI occurred in 93 patients (Table 1); 15 (16%) patients had ≥ 2 VGS-BSI. 80 (86%) patients had fever and neutropenia (F&N); 26 (28%) required ICU care for vasopressors (N=17, 18%) or mechanical ventilation (N=10, 11%). Most VGS isolates were S. mitis/oralis group. In total, 15 (16%) patients received LVXp ≤ 6 months before VGS-BSI; 9 (10%) had breakthrough VGS-BSI while receiving LVXp and all isolates were LVX resistant. Figure 1 shows susceptibilities: overall, 24% of isolates had frank resistance to PCN, 19% CEF, 13% LVX; all were VAN susceptible. When evaluating for changes in susceptibilities over time, there was a significant difference in the proportion of LVX-resistant isolates (p=0.009, Cochran-Armitage χ 2), but not CEF (p=0.08) or PCN (p=0.86).Table 1. Demographic and Clinical Characteristics of Immunocompromised Children with Viridans Group Streptococci Bloodstream Infections (VGS-BSI) Figure 1. Antimicrobial Susceptibility Profile of Viridans Group Streptococci Bloodstream Isolates from Immunocompromised children, 2010-2021. Of 111 VGS-BSI reported during the study period from immunocompromised children, 83 (75%) were available for further testing. Antimicrobial susceptibility testing was performed by Etest and interpreted per CLSI M100. Susceptibility profiles to penicillin (PCN), cefepime (CEP) and, levofloxacin (LVX) are shown. Abbreviations: S—susceptible, I—intermediate, R—resistant. ConclusionBreakthrough, LVX-resistant VGS-BSI occurred in 10% of patients, most frequently in children with AML or HCT. Over time, there was a trend towards increased LVX resistance in the cohort. Routine antimicrobial testing and ongoing monitoring for emergence of resistance are warranted to inform local prophylaxis and empirical antibiotic strategies for high-risk children with F&N.Disclosures Monica I. Ardura, DO, MSCS, Shire (Grant/Research Support)

Antibiogram profiles and efficacy of antibiotic regimens of bacterial isolates from chronic osteomyelitis of the appendicular skeleton: A developing-world perspective

Background. Empirical antibiotic strategies in the treatment of chronic osteomyelitis should ideally be based on local microbiological antibiograms. Objectives. To review the antibiogram profiles of bacterial isolates of patients undergoing surgical treatment for chronic osteomyelitis and identify the most appropriate empirical antibiotic strategy. Methods. A retrospective review of clinical records and microbial culture reports was performed for all patients who underwent treatment for chronic osteomyelitis at two orthopaedic units in Western Cape Province, South Africa, between March 2016 and December 2019. Reported antibiotic susceptibility data were used to predict the potential efficacy of different empirical antibiotic regimens, according to underlying aetiology (fracture related, contiguous, haematogenous). Results. Two hundred patients with chronic osteomyelitis of the appendicular skeleton underwent surgical management. Antibiogram profiles for 218 organisms, isolated from 169 patients, were evaluated. Staphylococcus aureus (41%) and Enterobacterales (30%) were the most common organisms isolated. The combinations of meropenem plus vancomycin, and piperacillin-tazobactam plus amikacin plus vancomycin, as empirical postoperative antibiotics would both effectively treat 78% of chronic osteomyelitis cases overall. The most effective practical oral combinations were co-amoxiclav plus ciprofloxacin (61%) and co-trimoxazole plus ciprofloxacin (61%). Conclusions. This study reports antibiogram profiles in the developing-world setting that could potentially guide empirical antibiotic choices in the management of chronic osteomyelitis.

Epidemiology and Effects of Bacterial Infections in Patients With Cirrhosis Worldwide

Bacterial infections are common and life-threatening in patients with cirrhosis. Little is known about the epidemiology of bacterial infections in different regions. We performed a multicenter prospective intercontinental study to assess the prevalence and outcomes of bacterial and fungal infections in patients with cirrhosis. We collected data from 1302 hospitalized patients with cirrhosis and bacterial or fungal infections at 46 centers (15 in Asia, 15 in Europe, 11 in South America, and 5 in North America) from October 2015 through September 2016. We obtained demographic, clinical, microbiology, and treatment data at time of diagnosis of infection and during hospitalization. Patients were followed until death, liver transplantation, or discharge. The global prevalence of multidrug-resistant (MDR) bacteria was 34% (95% confidence interval 31%-37%). The prevalence of MDR bacteria differed significantly among geographic areas, with the greatest prevalence in Asia. Independent risk factors for infection with MDR bacteria were infection in Asia (particularly in India), use of antibiotics in the 3 months before hospitalization, prior health care exposure, and site of infection. Infections caused by MDR bacteria were associated with a lower rate of resolution of infection, a higher incidence of shock and new organ failures, and higher in-hospital mortality than those caused by non-MDR bacteria. Administration of adequate empirical antibiotic treatment was independently associated with improved in-hospital and 28-day survival. In a worldwide study of hospitalized patients, we found a high prevalence of infection with MDR bacteria in patients with cirrhosis. Differences in the prevalence of MDR bacterial infections in different global regions indicate the need for different empirical antibiotic strategies in different continents and countries. While we await new antibiotics, effort should be made to decrease the spread of MDR bacteria in patients with cirrhosis.

Clinical Monitoring of Well-Appearing Infants Born to Mothers With Chorioamnionitis.

The risk of early-onset sepsis is low in well-appearing late-preterm and term infants even in the setting of chorioamnionitis. The empirical antibiotic strategies for chorioamnionitis-exposed infants that are recommended by national guidelines result in antibiotic exposure for numerous well-appearing, uninfected infants. We aimed to reduce unnecessary antibiotic use in chorioamnionitis-exposed infants through the implementation of a treatment approach that focused on clinical presentation to determine the need for antibiotics. Within a quality-improvement framework, a new treatment approach was implemented in March 2015. Well-appearing late-preterm and term infants who were exposed to chorioamnionitis were clinically monitored for at least 24 hours in a level II nursery; those who remained well appearing received no laboratory testing or antibiotics and were transferred to the level I nursery or discharged from the hospital. Newborns who became symptomatic were further evaluated and/or treated with antibiotics. Antibiotic use, laboratory testing, culture results, and clinical outcomes were collected. Among 277 well-appearing, chorioamnionitis-exposed infants, 32 (11.6%) received antibiotics during the first 15 months of the quality-improvement initiative. No cases of culture result-positive early-onset sepsis occurred. No infant required intubation or inotropic support. Only 48 of 277 (17%) patients had sepsis laboratory testing. The implementation of the new approach was associated with a 55% reduction (95% confidence interval 40%-65%) in antibiotic exposure across all infants ≥34 weeks' gestation born at our hospital. A management approach using clinical presentation to determine the need for antibiotics in chorioamnionitis-exposed infants was successful in reducing antibiotic exposure and was not associated with any clinically relevant delays in care or adverse outcomes.

Empirical therapies among adults hospitalized for community-acquired upper urinary tract infections: A decision-tree analysis of mortality, costs, and resistance

Poor outcomes occur when patients with serious infections receive antibiotics to which the organisms are resistant. Decision trees simulated in-hospital mortality, costs, incremental cost-effectiveness ratio per life year saved, and carbapenem resistance according to 3 empirical antibiotic strategies among adults hospitalized for community-acquired (CA) upper urinary tract infections (UTIs): ceftriaxone (CRO) plus gentamicin (GM) in the intensive care unit (ICU), imipenem (IMP), and individualized choice (IMP or CRO) based on clinical risk factors for CA- extended-spectrum β-lactamase (ESBL). The estimated prevalence of CA-ESBL on admission was 5% (range, 1.3%-17.6%); 3% and 97% were admitted to the ICU and medical ward (MW), respectively. In the ICU, CROplusGM was dominated; IMP was cost-effective (incremental cost-effectiveness ratio: €4,400 per life year saved compared with individualized choice). In the MW, IMP had no impact on mortality and was less costly (-€142 per patient vs CRO,-€38 vs individualized choice). The dominance of IMP was consistent in sensitivity analyses. Compared with CRO, colonization by carbapenem-resistant pathogens increased by an odds ratio of 4.5 in the IMP strategy. Among the ICU patients, empirical IMP therapy reduces mortality at an acceptable cost. Among MW patients, individualized choice or CRO is preferred to limit carbapenem resistance at a reasonable cost.

Bacterial Infections in Cirrhosis: Prevention and Treatment

Bacterial infection is a frequent complication in patients with advanced cirrhosis. Incidence ranges between 25 and 30 %. Most common infections are spontaneous bacterial peritonitis and urinary infections followed by pneumonia, skin/soft tissue infections and bacteremia. Cirrhosis increases the risk to develop sepsis, severe sepsis and death. Therefore, early diagnosis and adequate treatment of infection is essential in the management of these patients. Recent data show that currently recommended empirical antibiotic strategies (β-lactams) fail frequently in nosocomial and healthcare associated infections in cirrhosis, a feature that is related to the higher prevalence of multidrug resistant bacteria in infections acquired in the healthcare environment. Empirical antibiotic treatment should therefore be selected according not only to the type and severity of infection but also to the site of acquisition of infection. Antibiotic guidelines should be tailored according to the local epidemiological pattern of multiresistance.

An Australian survey of clinical practices in management of neutropenic fever in adult cancer patients 2009

An abundance of new evidence regarding treatment strategies for neutropenic fever is likely to contribute to variability in practice across institutions and clinicians alike. To describe current clinical practices in Australia, by surveying haematologists, oncologists and infectious diseases physicians involved in cancer care. Clinician members from Australian professional associations, accounting for the vast majority of Australian cancer specialists, were invited to participate in an electronic survey, comprising of a clinical case-based questionnaire. Clinical practice areas explored were: use of risk-assessment and empiric antibiotic strategies across various treatment settings; use of anti-bacterial prophylaxis; and use of granulocyte-colony stimulating factors for established neutropenic fever and for secondary prophylaxis. A total of 252 clinicians returned responses (approximately 30% response rate). The majority (>70%) were representative of practices in public, major city, tertiary referral hospitals. Less than half of clinicians were aware of risk-assessment tools and less than quarter currently used ambulatory care strategies. If adequate resources were made available, more than 80% were willing to use risk-assessment tools and 60% more clinicians were likely to use ambulatory care strategies. Most clinicians prescribed dual therapy parenteral antibiotics, even for clinically stable patients (53% haematologists, 56% oncologists). Granulocyte-colony stimulating factor was used frequently as secondary prophylaxis in the breast cancer case (91%), follicular lymphoma case (59%) and non-small cell lung cancer case (31%). Fluoroquinolone prophylaxis was infrequently prescribed (19% oncologists, 30% haematologists). Evidence-practice gaps were identified around the use of risk-assessment-based empiric therapy, and help to inform better clinical guidance.

Neumonía asociada a la ventilación mecánica

The second most important infectious complication in hospitalized patients is pneumonia, this occupying the first place in the Intensive Care Units (ICU). Approximately 80% of the episodes of nosocomial pneumonia occur in patients with an artificial airway, which is called ventilation-associated pneumonia (VAP). VAP is the most frequent cause of mortality among nosocomial infections in the ICU, mainly if they are caused by Pseudomonas aeruginosa and Methicillin-resistant Staphylococcus aureus (MRSA). It also increases days of mechanical ventilation and length of stay in the ICU and hospital. In spite of the available diagnostic procedures, the diagnosis of VAP continues to be a clinical one. The presence of X-ray infiltrates and purulent endotracheal secretions are the essential conditions for the diagnosis. We should also evaluate the patient's condition and the risk factors for difficult-to-treat pathogens. If the VAP is early and there are no risk factors, most of the empiric antibiotic strategies will provide correct coverage of the flora found. However, if the diagnosis of VAP is made in a patient who has been receiving mechanical ventilation for more than one week, under antibiotic use, with risk factors for multirresistant pathogens, we should individualize the empiric antibiotic treatment.

Antibiotic Selection for Purulent Skin and Soft-Tissue Infections in Ambulatory Care: A Decision-Analytic Approach

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has caused a nationwide epidemic of skin and soft-tissue infections in ambulatory pediatrics. Antibiotic treatment recommendations suggest incorporating local epidemiology for the prevalence of CA-MRSA. We sought to identify the antibiotic strategy with the highest probability of activity and to identify threshold values for epidemiologic variables including bacterial prevalence and antibiotic resistance. We used decision analysis to evaluate 3 empiric antibiotic strategies: clindamycin, trimethoprim/sulfamethoxazole (T/S), and cephalexin. We calculated the probability of activity against the bacteria causing the infection (CA-MRSA, methicillin-sensitive S. aureus and group A Streptococcus [GAS]) by incorporating estimates of prevalence and antibiotic resistance to determine the optimal strategy. Sensitivity analysis was used to identify thresholds for prevalence and antibiotic resistance where 2 strategies were equal. Clindamycin (0.95) and T/S (0.89) had substantially higher probability of activity than cephalexin (0.28) using baseline estimates for bacterial prevalence and antibiotic resistance. Cephalexin was the optimal antibiotic only when CA-MRSA prevalence was <10%. The probability of activity for clindamycin and T/S was highly sensitive to changes in the values for bacterial prevalence (both CA-MRSA and GAS) and CA-MRSA resistance to clindamycin. Empiric treatment of skin and soft-tissue infections with either clindamycin or T/S maximizes the probability that the antibiotic will be active when CA-MRSA prevalence is >10%. Deciding between T/S and clindamycin requires consideration of antibiotic resistance and prevalence of GAS. This model can be customized to local communities and illustrates the importance of ongoing epidemiologic surveillance in primary care settings.

Infecciones asociadas a los dispositivos utilizados para la ventilación asistida

The second most important infectious complication in hospitalised patients is pneumonia, and it hits first place in the Intensive Care Unit (ICU). Almost 80% of the episodes of health-care pneumonia happens when patient is under mechanical ventilation, causing ventilator-associated pneumonia (VAP). VAP is associated with the highest rates of mortality in ICU infections, mainly if due to Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA). It also increases days under mechanical ventilation and the length of stay in ICU and hospital. Although all the diagnostic procedures, the diagnosis of VAP is based basically in the clinics: X-ray infiltrates and purulent endotracheal secretions are the cornerstone of the diagnosis. We should evaluate and screen any risk factor for multiresistant pathogens. If we have an early VAP and no risk factors, the majority of empiric antibiotic strategies are useful, but if we have a patient with more than one week under mechanical ventilation, previous antibiotic use, and risk factors for multiresistant pathogens, we should then individualize empiric antibiotic treatment.

Impact of diversity of antibiotic use on the development of antimicrobial resistance

To evaluate the impact of different antibiotic strategies on acquisition of resistant microorganisms. A prospective study was conducted over a 44 month period in a single ICU. Four empirical antibiotic strategies for ventilator-associated pneumonia (VAP) were sequentially implemented. Over the initial 10 months, patient-specific antibiotic therapy was prescribed; then, 4 month periods of prioritization or restriction rotation cycles of various antimicrobial agents were implemented for a total of 24 months; and, finally, during the last 10 months (mixing period) the first-line antibiotic for VAP was changed following a pre-established schedule to ensure maximum heterogeneity. Antibiotic consumption was closely monitored every month, and antimicrobial resistance patterns were regularly assessed. Antimicrobial heterogeneity was estimated using a modified Peterson index (AHI) measuring the ratios for the five most used antibiotics. Colonization by targeted microorganisms and susceptibility patterns were compared with the patient-specific period. Higher diversity of antibiotic prescription was obtained during patient-specific therapy (AHI = 0.93) or mixing periods (AHI = 0.95) than during prioritization (AHI = 0.70) or restriction periods (AHI = 0.68). High homogeneity was associated with increases in carbapenem-resistant Acinetobacter baumannii (CR-Ab) [relative risk (RR) 15.5; 95%CI 5.5-42.8], extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae (RR 4.2; 95%CI 1.9-9.3) and Enterococcus faecalis (RR 1.7; 95%CI 1.1-2.9). During the restriction period, incidence of ESBL-producing Enterobacteriaceae and E. faecalis returned to patient-specific rates but CR-Ab remained higher. Antibiotic prescription patterns balancing the use of different antimicrobials should be promoted to reduce the selection pressure that aids the development of resistance.