Broad-spectrum Empirical Antimicrobial Therapy Research Articles

Effect of Empirical Antimicrobial Therapy of Piperacillin-tazobactam Versus Carbapenems on Mortality for Patients with Sepsis from Nursing Homes.

Background Nursing home residents with a high risk of multidrug-resistant organism infection pose a complex challenge to broad-spectrum empirical antimicrobial therapy, particularly those infected with extended-spectrum β-lactamase-producing Enterobacteriaceae. The present study compared the efficacy of piperacillin-tazobactam and carbapenems as empirical antimicrobial treatments for patients with sepsis from nursing homes. Patients and Methods Using a nationwide inpatient database in Japan, we identified patients diagnosed with sepsis within two days of admission from nursing homes between 2018 and 2021. We selected patients who received intravenous piperacillin-tazobactam or carbapenems within two days of admission. In-hospital mortality was compared between the piperacillin-tazobactam and carbapenem groups using inverse probability of treatment weighting. Result We identified 8,025 eligible patients. Of these, 3,391 (42%) received piperacillin-tazobactam, and 4,634 (58%) received carbapenems within 2 days of admission. The inverse probability of treatment weighting analysis showed no significant difference in in-hospital mortality between the groups (31.6% in the piperacillin-tazobactam group and 32.8% in the carbapenem group; risk difference, 1.2%; 95% confidence interval, -3.2% to 0.9%). Conclusions Carbapenems and piperacillin-tazobactam as empirical antimicrobial therapy in patients with sepsis from nursing homes were associated with comparable in-hospital mortality rates. These findings highlight the importance of making decisions regarding broad-spectrum empirical antimicrobial therapy.

Pediatric Sepsis Diagnosis, Management, and Sub-phenotypes.

Sepsis and septic shock are major causes of morbidity, mortality, and health care costs for children worldwide, including >3 million deaths annually and, among survivors, risk for new or worsening functional impairments, including reduced quality of life, new respiratory, nutritional, or technological assistance, and recurrent severe infections. Advances in understanding sepsis pathophysiology highlight a need to update the definition and diagnostic criteria for pediatric sepsis and septic shock, whereas new data support an increasing role for automated screening algorithms and biomarker combinations to assist earlier recognition. Once sepsis or septic shock is suspected, attention to prompt initiation of broad-spectrum empiric antimicrobial therapy, fluid resuscitation, and vasoactive medications remain key components to initial management with several new and ongoing studies offering new insights into how to optimize this approach. Ultimately, a key goal is for screening to encompass as many children as possible at risk for sepsis and trigger early treatment without increasing unnecessary broad-spectrum antibiotics and preventable hospitalizations. Although the role for adjunctive treatment with corticosteroids and other metabolic therapies remains incompletely defined, ongoing studies will soon offer updated guidance for optimal use. Finally, we are increasingly moving toward an era in which precision therapeutics will bring novel strategies to improve outcomes, especially for the subset of children with sepsis-induced multiple organ dysfunction syndrome and sepsis subphenotypes for whom antibiotics, fluid, vasoactive medications, and supportive care remain insufficient.

Safety of De-Escalating Empiric Antimicrobial Agents in Trauma Patients with Indigenous Oral Flora Ventilator-Associated Pneumonia.

Background: Ventilator-associated pneumonia (VAP) is a frequently occurring nosocomial infection in critically ill trauma patients. When bronchoalveolar lavage (BAL) returns with indigenous oral flora (IOF), de-escalating antimicrobial therapy is challenging. Patients and Methods: This is a retrospective review of trauma patients who received broad-spectrum empiric antimicrobial therapy for clinical VAP, and whose BAL culture resulted with >100,000 CFU/mL of IOF from September 1, 2017 to September 1, 2020. Patients were identified using the trauma database and microbiology reports of BALs with IOF. This review evaluated the effect of antibiotic de-escalation on recurrent or persistent pneumonia. Results: Of 51 trauma patients with clinical VAP and IOF, 18 patients (35.3%) had antimicrobial agents de-escalated. De-escalation was driven primarily by the discontinuation of vancomycin, with the continuation of a β-lactam antibiotic as monotherapy for the remainder of the treatment course (n = 15; 86.7%). The overall rate of either persistent or recurrent VAP in the cohort was 10%, and this did not differ statistically between those who received de-escalation therapy after isolation of IOF and those who did not (16.7% vs. 6.1%; p = 0.224), however, the incidence of acute kidney injury (AKI) was higher in the non-de-escalation group (39.4% vs. 11.1%; p = 0.034). There was no statistical difference in ventilator days, intensive care unit (ICU) length of stay, or hospital length of stay between treatment groups. Conclusions: Trauma patients who develop VAP with isolated BAL cultures of IOF or mixed flora can safely have anti-methicilllin-resistant Staphylococcus aureus (MRSA) antimicrobial agents discontinued, and this may result in decreased rates of AKI.

Risk Factors for 30-Day Mortality in Neonatal Gram-Negative Bacilli Sepsis.

Multidrug-resistant gram-negative bacilli (MDR-GNB) have emerged globally as a serious threat and with a high case fatality rate (CFR). We performed a case-control study in a Thai neonatal intensive care unit to identify the risk factors for 30-day CFR of GNB sepsis between 1991 and 2017. The CFR was analyzed by Cox's proportional hazards model. For 27 years, the percentage of MDR-GNB from GNB sepsis was 66% (169/257). The medians (interquartile ranges) of gestational age and birth weight of the neonates with GNB sepsis were 33 (29-38) weeks and 1,817 (1,100-2,800) grams, respectively. The 30-day CFRs of the neonates with MDR-GNB and non-MDR-GNB sepsis were 33% (56/169) and 20% (18/88), respectively, (hazard ratio [HR] = 1.74; 95% confidence interval [CI]: 1.03-2.97; p = 0.04). Using Cox's proportional hazards model, nonsurvivors in GNB sepsis were more likely to have septic shock (adjusted HR [aHR] = 6.67; 95% CI: 3.28-13.57; p < 0.001) or no microbiological cure (aHR = 10.65; 95% CI: 4.98-22.76; p < 0.001) than survivors. Neonates suspected of sepsis with septic shock need broad-spectrum empirical antimicrobial therapy until the second successive negative culture, especially in high MDR areas.

Necrotizing Fasciitis and Methicillin Resistant Staphylococcus Aureus

Necrotizing fasciitis (NF) is an aggressive and life-threatening infection of skin and soft tissue characterized by widespread fascial necrosis which leads to morbidity and mortality if left untreated. There is difficulty in managing this condition because there is a combination of difficulty in diagnosis, and also of early as well as late management. It can be caused by either a single organism or more frequently by a variety of microbes - both aerobic and anaerobic. Necrotizing fasciitis seems to have preponderance in males, perhaps due to increased incidence of trauma in males. Staphylococcus aureus is the most prevalent pathogen in hospitals and communities and MRSA has become a common isolate associated with skin and soft tissue infections over the past few years, monomicrobial MRSA necrotizing fasciitis has been reported only in a few studies. Early surgical intervention, early diagnosis and aggressive treatment should be done. Material and Methods: All patients were diagnosed as NF on surgical report. Surgical exploration is undertaken after resuscitation. Penicillin along with, an amino glycoside and clindamycin or metronidazole is administered preoperatively in moribund patients. Cefoxitin or imipenem or meropenem is used in more limited infections. Fair amount of desloughing is done without anesthesia. Overlying fat as patchy greenish-black liquefaction necrotic tissues are excised primarily, and specimen sent for culture in microbiology department. Cultures were processed the susceptibility of S. aureus isolates to antimicrobials was done. Results: A total of 200 hospitalized patients those who were surgically treated for NF were included in the study. Of the 200 patients 42 patients were culture positive for MRSA. In our study mean age was 56± 11.21 of which 124 (62%) were male , mean hospitalization days were 16.5± 6.2. patients with underlying diabetes mellitus were 66 (33%) and hypertension were 74(37%). In MRSA group (n=42) mean age was 53 ± 9.22. Male were 36 (73.81%) , mean hospitalization days were 17.6 ± 6.2. patients with underlying diabetes mellitus were 21 (50%) and hypertension were 19(45.24%).42 (21%) were MRSA, 31 (15.5%) were MSSA, 21 (10.5%) were coagulase negative staphylococcus, 4(2%) were Streptococcus group A, 11 (5.5%) were Streptococcus species, 6 (3%) were Bacillus species, 24 (12 %) were Escherichia coli, 19 (9.5%) were Acinetobacter species, 3 (1.5%) were Candida albicans and in 30 (15%) no growth was observed in culture. Discussion and Conclusion: Some experts recommend use of broad-spectrum empirical antimicrobial therapy for suspected cases of necrotizing fasciitis and therapy directed against MRSA is not a standard practice. For treatment selection of appropriate antimicrobial agents for any suspected necrotizing fasciitis must take into account the nature of patient's exposure and local epidemiologic data but no reliable epidemiological or clinical risk factors with MRSA from those infected with MSSA or non-S. aureus are available. In our study mean age of patients diagnosed NF was 53 ± 9.22. While male were 36 (73.81%). In study by Cheng NC et al. the median age was 62 years (range, 12-81 years) There was male predominance in NF by MRSA in our study . In our study lesions on extremities had better prognosis similar results were shown in other study. Necrotizing fasciitis caused by MRSA is a challenge to the treating surgeon. Prompt diagnosis and surgical management with empiric MRSA cover in areas where community acquired MRSA (CA-MRSA) is endemic. Lesions of extremities have better prognosis where MRSA infection is becoming endemic and empirical treatment of suspected necrotizing fasciitis or pneumonia should include active MRSA cover.

Fournier's Gangrene: Clinical Presentation of 13 Cases.

BackgroundFournier’s gangrene (FG) is a fulminant form of infective, polymicrobial, necrotizing fasciitis of the perineal, genital, and perianal regions. It commonly affects men, but women and children may also develop this type of tissue necrosis.Material/MethodsThis study is a retrospective analysis of the management of 13 cases of Fournier’s gangrene, diagnosed from among about 45 000 patients (men, women, and children) treated in the Department of General, Oncological, and Functional Urology (Medical University of Warsaw) from 1995 to 2013. All patients with Fournier’s gangrene underwent adequate surgical debridement of the necrotic tissues. Additional procedures (suprapubic cystostomy and orchiectomy) were necessary in 10 out of 13 (77.0%) patients. Seven out of 13 (53.8%) patients required subsequent reconstructive surgery of the scrotum.ResultsAll 13 patients were males, with a median age of 59.6 years (range: 42–68 years). The average hospital stay was 31.9 days (range: 16–46 days). None of our patients died due to Fournier’s gangrene. Bacteriological cultures of samples from the wounds showed polymicrobial flora, including the following genera of aerobes and anaerobes: Escherichia, Proteus, Klebsiella, Moraxella, Gemella, Enterococcus, Streptococcus, Staphylococcus, Bacteroides, Pseudoflavonifractor, Parabacteroides, Porphyromonas, Prevotella, Peptoniphilus, Peptostreptococcus, Actinomyces, Collinsella, and Lactobacillus.ConclusionsFavorable outcome of FG treatment with low morbidity and no mortality can be achieved with rapid diagnosis, urgent surgical debridement of all necrotic tissues, and broad-spectrum empirical antimicrobial therapy, usually with combined antibiotics, against aerobic and anaerobic bacteria. Prevention of uroseptic shock by treating localized infection is compulsory.

Outcomes Associated With Antimicrobial De-escalation of Treatment for Pneumonia Within the Veterans Healthcare Administration.

De-escalation, an antimicrobial stewardship concept, involves narrowing broad-spectrum empiric antimicrobial therapy based on clinical data. Current health outcomes evidence is lacking to support de-escalation. Studying Veterans Healthcare Administration pneumonia patients, de-escalation was associated with improved length of stay without affecting 30-day readmission or 30-day Clostridium difficile infection rates.

Severe Ebola virus disease with vascular leakage and multiorgan failure: treatment of a patient in intensive care

In the current epidemic of Ebola virus disease in western Africa, many aid workers have become infected. Some of these aid workers have been transferred to specialised hospitals in Europe and the USA for intensified treatment, providing the potential for unique insight into the clinical course of Ebola virus disease under optimised supportive measures in isolation units. A 38-year-old male doctor who had contracted an Ebola virus infection in Sierra Leone was airlifted to University Hospital Frankfurt, Germany, on day 5 after disease onset. Within 72 h of admission to the hospital's high-level isolation unit, the patient developed signs of severe multiorgan failure, including lungs, kidneys, and gastrointestinal tract. In addition to clinical parameters, the diagnostic work-up included radiography, ultrasound, pulse contour cardiac output technology, and microbiological and clinical chemistry analyses. Respiratory failure with pulmonary oedema and biophysical evidence of vascular leak syndrome needed mechanical ventilation. The patient received a 3 day treatment course with FX06 (MChE-F4Pharma, Vienna, Austria), a fibrin-derived peptide under clinical development for vascular leak syndrome. After FX06 administration and concurrent detection of Ebola-virus-specific antibodies and a fall in viral load, vascular leak syndrome and respiratory parameters substantially improved. We gave broad-spectrum empiric antimicrobial therapy and the patient needed intermittent renal replacement therapy. The patient fully recovered. This case report shows the feasibility of delivery of successful intensive care therapy to patients with Ebola virus disease under biosafety level 4 conditions. The effective treatment of vascular leakage and multiorgan failure by combination of ventilatory support, antibiotic treatment, and renal replacement therapy can sustain a patient with severe Ebola virus disease until virological remission. FX06 could potentially be a valuable agent in contribution to supportive therapy. University Hospital of Frankfurt.

Visual compatibility of micafungin sodium and levofloxacin injections

Micafungin and levofloxacin are often used in combination as part of broad-spectrum empirical antimicrobial therapy in hospitalized patients. Guidelines from the Infectious Diseases Society of America recommend the use of micafungin and levofloxacin concomitantly as alternative therapy in high-risk

The Use of Antimicrobial Agents in Children With Fever During Chemotherapy-induced Neutropenia

Children with fever and chemotherapy-induced or cancer-associated neutropenia should be assessed with complete history and physical examinations, undergo appropriate diagnostic studies, and promptly receive broad-spectrum empirical antimicrobial therapy. Assessment of risk for severe infection is crucial in determining the appropriate antimicrobial, route, venue, and duration of empirical antimicrobial therapy and need for prophylactic antimicrobial agents.

Health-Care-Associated Pneumonia

Health-Care-Associated Pneumonia

Prehospital administered intravenous antimicrobial protocol for septic shock: a prospective randomized clinical trial

Appropriate intravenous, broad-spectrum empiric antimicrobial therapy should be initiated as rapidly as possible for suspected severe infections in the presence of hypotension. Timing and delay of initial administration of effective antimicrobial therapy is an important predictor of survival [1]. It is hypothesized that appropriate prehospital-initiated intravenous, broad-spectrum empiric antimicrobial therapy will reduce the delay of administration and will reduce mortality [2].

Article Commentary: Strategies in the Prevention and Management of Ventilator-Associated Pneumonia

Ventilator-associated pneumonia (VAP) is a leading cause of morbidity and mortality in the intensive care unit. Prevention of VAP is possible through the use of several evidence-based strategies intended to minimize intubation, the duration of mechanical ventilation, and the risk of aspiration of oropharyngeal pathogens. Current data favor the quantitative analysis of lower respiratory tract cultures for the diagnosis of VAP, accompanied by the initiation of broad-spectrum empiric antimicrobial therapy based on patient risk factors for infection with multi-drug-resistant pathogens and data from unit-specific antibiograms. Eventual choice of antibiotic and duration of therapy are selected based on culture results and patient stability, with an emphasis on minimization of unnecessary antibiotic use.

Empiric Treatment of Nosocomial Intra-Abdominal Infections: A Focus on the Carbapenems

Serious nosocomial intra-abdominal infections are associated with high morbidity and mortality and represent a substantial drain on healthcare resources. Effective management of this type of infection requires the early use of appropriate, broad-spectrum empiric antimicrobial therapy. The consequences of delayed or inappropriate antimicrobial treatment can be severe-leading to an increased risk of death, re-operation, or prolonged hospitalization. Therefore, it is necessary to begin treatment as soon as possible with the most appropriate regimen, in terms of spectrum, timing, and duration. Review of pertinent English-language literature. Serious nosocomial intra-abdominal infections require broad-spectrum coverage because of the wide range of possible pathogens, which include difficult-to-treat organisms such as Pseudomonas aeruginosa and Bacteroides spp., and resistant strains of Klebsiella spp., Escherichia coli, and methicillin-resistant Staphylococcus aureus acquired from the hospital flora. The early use of appropriate, broad-spectrum empiric antimicrobial therapy for treating high-risk patients with intra-abdominal infections is considered, and appropriate use of the carbapenems, meropenem, and imipenem/cilastatin, is described. The carbapenems meropenem and imipenem/cilastatin have a spectrum of antimicrobial activity that covers the majority of expected pathogens, including anaerobes, as well as difficult-to-treat and resistant gram-negative strains. Early and appropriate use can reduce mortality and morbidity. Data from published clinical trials support the clinical effectiveness of these two carbapenems in intra-abdominal infections.

Management of severe sepsis: integration of multiple pharmacologic interventions.

Severe sepsis is an infection-induced process that often promotes organ dysfunction and death in up to 50% of afflicted patients. Clinical advances that improve patient survival include early goal-directed volume resuscitation, broad-spectrum empiric antimicrobial therapy with deescalation strategies, therapy with drotrecogin alfa (activated), glucocorticoid replacement in patients with adrenal insufficiency, and tight control of blood glucose levels. The challenge for critical care practitioners is to integrate the many pharmacologic and supportive interventions required for optimal care of these patients.

Management of Pulmonary Infections in Kidney Transplant Patients

Kidney transplantation is a cost-effective alternative for the treatment of end-stage renal disease, with clear survival and quality of life benefits. Infection is an important drawback in kidney transplantation and is second only to cardiovascular disease as a cause of death. Pulmonary infections occur in 8%-16% of all kidney transplant patients, with mortality ranging from 12%–16% in more recent studies. Bacteria as a group, Cytomegalovirus, Pneumocystis carinii, Legionella, and fungi, are the main agents. Although noninvasive methods are recommended for etiologic diagnosis, bronchoscopy or open lung biopsy is mandatory in the great majority of the cases. Both transbronchial biopsy and open lung biopsy provide more information about the etiologic agent compared with bronchoalveolar lavage alone, and open lung biopsy has a higher diagnostic yield, although it may be associated with more frequent and serious adverse events. Broad-spectrum empiric antimicrobial therapy should be instituted at the same time as an invasive diagnostic method is performed and treatment adjusted according to subsequent results. Empiric antimicrobial treatment and the invasive diagnostic method should be selected according to the severity of respiratory impairment, time of onset of disease after transplantation, the radiologic pattern, and specific epidemiological factors.