Aztreonam-avibactam for the treatment of intra-abdominal infections.

INTRODUCTION: Intra-abdominal infections are becoming increasingly common and can lead to significant morbidity and mortality. The incidence of these infections due to resistant gram-negative organisms is also increasing. Given this resistance, new antibiotic combinations are being developed, often utilizing older antibiotics and newer ß-lactamase inhibitors. Aztreonam/avibactam (ATM-AVI) is one of the combination antibiotics, which combines aztreonam, a monobactam, with avibactam, a broad-spectrum ß-lactamase inhibitor for the treatment of complicated intra-abdominal infections in combination with metronidazole. AREAS COVERED: In this drug evaluation manuscript, we provide an overview of intra-abdominal infections and an overview of currently available antimicrobial agents used to treat these infections. ATM-AVI is introduced, including chemistry, pharmacodynamics, pharmacokinetics and clinical studies of this compound. EXPERT OPINION: There are limited treatment options for complicated intra-abdominal infections due to resistant gram-negative organisms, especially those with metallo-ß-lactamases. One treatment option for these infections is ATM-AVI, which was recently approved in Europe, in addition to metronidazole. These bacteria are difficult to treat, and this new compound is a safe and effective option for empiric treatment in places with a high incidence of infections due to these bacteria, and also treatment for infections when these resistant bacteria are isolated in culture.

Surgical Infection Society Guidelines: 2022 Updated Guidelines for Antibiotic Use in Open Extremity Fractures.

Background: Open fractures, defined as fractures communicating with the environment through a skin wound, cause substantial morbidity after traumatic injury. Current evidence supports administration of prophylactic systemic antibiotic agents to patients with open extremity fractures to decrease infectious complications. Methods: The Therapeutic and Guidelines Committee of The Surgical Infection Society convened to revise guidelines for antibiotic use in open fractures. PubMed was queried for pertinent studies. Evaluation of the published evidence was performed using the GRADE framework. All committee members voted to accept or reject each recommendation. Results: In type I or II open extremity fractures, we recommend against administration of extended-spectrum antibiotic coverage compared with gram-positive coverage alone to decrease infections complications, hospital length of stay or mortality. In type III open extremity fractures, we recommend antibiotic therapy for no more than 24 hrs after injury, in the absence of clinical signs of active infection, to decrease infectious complications, hospital length of stay or mortality, and we recommend against extended antimicrobial coverage beyond gram-positive organisms to decrease infectious complications, hospital length of stay or mortality. In type III open extremity fractures with associated bone loss, we recommend antibiotic therapy in addition to systemic therapy to decrease infectious complications. Conclusions: Although antibiotic agents remain a standard of care for infection prevention after open extremity fractures, our findings and surveys of clinical practice patterns clearly show that additional robust clinical trials are needed to provide stronger corroborating evidence.

Changes in exhaled 13CO2/12CO2 breath delta value as an early indicator of infection in intensive care unit patients.

BACKGROUND: We have developed a new, noninvasive predictive marker for onset of infection in surgical intensive care unit (ICU) patients. The exhaled CO2/CO2 ratio, or breath delta value (BDV), has been shown to be an early marker for infection in a proof of concept human study and in animal models of bacterial peritonitis. In these studies, the BDV changes during onset and progression of infection, and these changes precede physiological changes associated with infection. Earlier diagnosis and treatment will significantly reduce morbidity, mortality, hospitalization costs, and length of stay. The objective of this prospective, observational, multicenter study was to determine the predictive value of the BDV as an early diagnostic marker of infection. METHODS: Critically ill adults after trauma or acute care surgery with an expected length of stay longer than 5 days were enrolled. The BDV was obtained every 4 hours for 7 days and correlated to clinical infection diagnosis, serum C-reactive protein, and procalcitonin levels. Clinical infection diagnosis was made by an independent endpoint committee. This trial was registered at the US National Institutes of Health (ClinicalTrials.gov) NCT02327130. RESULTS: Groups were demographically similar (n = 20). Clinical infection diagnosis was confirmed on day 3.9 ± 0.63. Clinical suspicion of infection (defined by SIRS criteria and/or new antibiotic therapy) was on day 2.1 ± 0.5 in all infected patients. However, 5 (56%) of 9 noninfected subjects also met clinical suspicion criteria. The BDV significantly increased by 1‰ to 1.7‰ on day 2.1 after enrollment (p < 0.05) in subjects who developed infections, while it remained at baseline (± 0.5‰) for subjects without infections. CONCLUSION: A BDV greater than 1.4‰ accurately differentiates subjects who develop infections from those who do not and predicts the presence of infection up to 48 hours before clinical confirmation. The BDV may predict the onset of infection and aid in distinguishing SIRS from infection, which could prompt earlier diagnosis, earlier appropriate treatment, and improve outcomes. LEVEL OF EVIDENCE: Diagnostic test, level III.

Empiric Antibiotics for Sepsis.

BACKGROUND: Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. Early recognition and treatment are the cornerstones of management. METHODS: Review of the English-language literature. RESULTS: For both sepsis and septic shock "antimicrobials [should be] be initiated as soon as possible and within one hour" (Surviving Sepsis Campaign). The risk of progression from severe sepsis to septic shock increases 8% for each hour before antibiotics are started. Selection of antimicrobial agents is based on a combination of patient factors, predicted infecting organism(s), and local microbial resistance patterns. The initial drugs should have activity against typical gram-positive and gram-negative causative micro-organisms. Anaerobic coverage should be provided for intra-abdominal infections or others where anaerobes are significant pathogens. Empiric antifungal or antiviral therapy may be warranted. For patients with healthcare-associated infections, resistant micro-organisms will further complicate the choice of empiric antimicrobials. Recommendations are given for specific infections. CONCLUSION: Early administration of broad-spectrum antimicrobial drugs is one of the most important, if not the most important, treatment for patients with sepsis or septic shock. Drugs should be initiated as soon as possible, and the choice of should take into account patient factors, common local pathogens, hospital antibiograms and resistance patterns, and the suspected source of infection. Antimicrobial agent therapy should be de-escalated as soon as possible.

Antibiotic-Impregnated Central Venous Catheters Do Not Change Antibiotic Resistance Patterns.

BACKGROUND: Antibiotic-impregnated central venous catheters (CVCs) decrease the incidence of infection in high-risk patients. However, use of these catheters carries the hypothetical risk of inducing antibiotic resistance. We hypothesized that routine use of minocycline and rifampin-impregnated catheters (MR-CVC) in a single intensive care unit (ICU) would change the resistance profile for Staphylococcus aureus. METHODS: We reviewed antibiotic susceptibilities of S. aureus isolates obtained from blood cultures in a large urban teaching hospital from 2002-2015. Resistance patterns were compared before and after implementation of MR-CVC use in the surgical ICU (SICU) in August 2006. We also compared resistance patterns of S. aureus obtained in other ICUs and in non-ICU patients, in whom MR-CVCs were not used. RESULTS: Data for rifampin, oxacillin, and clindamycin were available for 9,703 cultures; tetracycline resistance data were available for 4,627 cultures. After implementation of MR-CVC use in the SICU, rifampin resistance remained unchanged, with rates the same as in other ICU and non-ICU populations (3%). After six years of use of MR-CVCs in the SICU, the rate of tetracycline resistance was unchanged in all facilities (1%-3%). The use of MR-CVCs was not associated with any change in S. aureus oxacillin-resistance rates in the SICU (66% vs. 60%). However, there was a significant decrease in S. aureus clindamycin resistance (59% vs. 34%; p < 0.05) in SICU patients. CONCLUSIONS: Routine use of rifampin-minocycline-impregnated CVCs in the SICU was not associated with increased resistance of S. aureus isolates to rifampin or tetracyclines.

Pharmacokinetics and Pharmacodynamics of Antimicrobials in Critically Ill Patients.

Critically ill patients with severe infections often have altered pharmacokinetic and pharmacodynamic variables that lead to challenging treatment decisions. These altered variables can often lead to inadequate dosing and poor treatment outcomes. The pharmacokinetic parameters include absorption, distribution, metabolism, and excretion. Pharmacodynamics is the relationship between drug serum concentrations and pharmacologic and toxicologic properties of the medication. In addition to these altered parameters, these critically ill patients frequently are receiving organ support in the forms of continuous renal replacement therapy or extra-corporeal membrane oxygenation. Altered pharmacodynamics can lead to decreased end-organ perfusion, which can ultimately lead to treatment failure or exposure-related toxicity. The most common antimicrobials utilized in the intensive care unit are classified by the pharmacodynamic principles of time-dependent, concentration-dependent, and concentration dependent with time-dependence. Thus, the aim of this review is to outline pharmacokinetic and pharmacodynamic changes of critically ill patients with severe infections and provide strategies for optimal antibiotic agent dosing in these patients.

Ceftazidime-avibactam for the treatment of complicated intra-abdominal infections.

INTRODUCTION: The treatment of complicated intra-abdominal infections (cIAI) is increasingly challenging due to increased resistance of Gram-negative organisms. These multidrug resistant organisms lead to an increase in morbidity and mortality. This has led to renewed interest in use of older ß-lactam antibiotics in combination with newer ß-lactamase inhibitors. Ceftazidime-avibactam is one of the newest such combination antibiotics, which has been released for treatment of complicated intra-abdominal infections in combination with metronidazole. Areas covered: In this drug evaluation manuscript cIAI along with the chemistry, pharmacodynamics, pharmacokinetics, metabolism and clinical study results of ceftazidime-avibactam are reviewed. Expert opinion: The role of ceftazidime-avibactam in combination with metronidazole in the treatment of cIAI is still to be defined. Patients with cIAI known to be infected with Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae would be clear candidates for treatment with this agent, as would patients infected with more common types of extended-spectrum ß-lactamase producing Gram-negative pathogens if a carbapenem alternative were desired. At present, it is difficult to establish a clear group of patients with cIAI for whom initial empiric therapy with this agent would be warranted.

Nutrition considerations surrounding restorative proctocolectomy.

Restorative proctocolectomy with ileal pouch-anal anastomosis has become the surgical treatment of choice for patients with ulcerative colitis and familial polyposis coli syndromes. Pouch construction uses the distal 30-40 cm of ileum, and there exists a potential for postoperative nutrition consequences. These include vitamin B(12) deficiency, iron deficiency, bile acid malabsorption, and abnormalities of trace elements, fluids, and electrolytes. Patients who have undergone an ileal pouch-anal anastomosis procedure often describe specific food sensitivities that may require diet alteration, even more so than do patients with permanent ileostomy. There may be roles for postoperative probiotic supplementation in an attempt to decrease the rate of "pouchitis" and appropriate preoperative nutrition support to minimize the risk of perioperative complications.