ro13-9904 and Communicable-Diseases

More than 30 years since it was developed for clinical use, the third-generation cephalosporin ceftriaxone remains the most commonly used agent for outpatient parental antimicrobial therapy (OPAT). Recent antimicrobial stewardship programmes have tended to restrict ceftriaxone use in hospitals to control antibiotic resistance and outbreaks of Clostridium difficle infection (CDI). Considering the expansion of OPAT programmes both in the UK and worldwide, revisiting the role of ceftriaxone in OPAT in the context of changing antimicrobial prescribing practices is timely.. To identify the evidence base for OPAT, review current and historical data on indications for, and safety of ceftriaxone within the OPAT setting, and to provide some perspectives on the future role of ceftriaxone.. We searched PubMed and Scopus for articles published in English, and hand searched reference lists. We also conducted a complementary descriptive analysis of prospectively acquired data on the use of ceftriaxone in more than 1,300 OPAT episodes over a 10-year period in our UK centre.. Ceftriaxone has an excellent safety profile in the OPAT setting, and its broad spectrum of activity makes it an established agent in a wide range of clinical infection syndromes, such as skin and soft-tissue infection, bone and joint infection, streptococcal endocarditis and several others. Intriguingly, in contrast to the inpatient setting, liberal use of ceftriaxone in OPAT has not been strongly linked to CDI, suggesting additional patient and environmental factors may be important in mediating CDI risk.

Topics: Ambulatory Care; Anti-Bacterial Agents; Ceftriaxone; Communicable Diseases; Humans; Infusions, Parenteral; Soft Tissue Infections

Ceftriaxone is a third-generation cephalosporin that is used for a variety of infections such as meningitis, gonorrhoea and community-acquired pneumonia. The most important aspects of its pharmacokinetics include a long half-life, excellent tissue penetration and saturable (dose-dependent) serum protein binding of the drug. A pharmacodynamic analysis [total area under the concentration-time curve (AUC)/minimum inhibitory concentration (MIC)] was performed in several populations (healthy volunteers, children, the elderly, and patients with renal and hepatic impairment) against various bacterial species (Streptococcus pneumoniae, the Enterobacteriacieae, methicillin-susceptible Staphylococcus aureus, and Pseudomonas aeruginosa). AUC/MIC [area under the inhibitory time curve (AUIC)] was chosen as the pharmacodynamic parameter for this analysis since ceftriaxone is a time-dependent killer and high peak concentrations are not needed. In addition, there is a significant correlation between AUIC, time when concentration exceeds the MIC (t > MIC) and time to eradication. Total and free AUICs (assuming a free fraction = 10%) were calculated since it is highly protein bound. It was postulated that a free AUIC of at least 125 would be required to achieve efficacy. From our analysis of these various populations, we were able to conclude that the free AUIC values support the use of Ig daily in infections where MIC values are below 2 mg/L. In addition, consistent with its reported good activity against CSF organisms with MICs < or =1.0 mg/L and marginal activity against organisms with MICs > or =2.0 mg/L, we also recommend the target free AUIC values of at least 125 for patients with severe infections such as meningitis. Patients with mild infections may recover with values below 125 but they may remain at risk of the development of resistant organisms. Furthermore, it is essential to further validate these findings in patients who have received treatment, calculate AUICs and correlate these parameters with both clinical and microbiological outcomes.

Topics: Adult; Aged; Area Under Curve; Ceftriaxone; Cephalosporins; Child; Communicable Diseases; Half-Life; Humans; Microbial Sensitivity Tests; Protein Binding

Cefotaxime has been used for the management of neonatal infections since the 1990s for suspected meningitis and to mitigate gentamicin-associated renal injury. Its shortage in 2015 and subsequent removal from the U.S. pharmaceutical market forced providers to consider alternatives. Ceftriaxone, a cephalosporin with an identical antibacterial spectrum of activity to cefotaxime, is contraindicated in neonates due to its risk of biliary pseudolithiasis. Ceftazidime was recommended as an alternative by the American Academy of Pediatrics but is inequivalent.. This article addresses indications for cephalosporin use and considerations when selecting an alternative to cefotaxime. Differences among cefotaxime, ceftriaxone, ceftazidime, and cefepime are discussed and compared to the standard-of-care presumptive regimen, ampicillin, and gentamicin. The authors consider the data behind the neonatal contraindication to ceftriaxone and provide recommendations for their application to practice.. The data against ceftriaxone use in neonates remain poor, particularly in the context of the cefotaxime shortage and lack of an equivalent alternative. Ceftriaxone could be considered in low-risk neonates without hyperbilirubinemia or exposure to calcium-containing fluids on a case-by-case basis. Ceftazidime monotherapy for presumptive management of neonatal infections is inappropriate; cefepime should be more frequently utilized in neonates who are poor candidates for ceftriaxone.

Topics: Ampicillin; Anti-Bacterial Agents; Calcium; Cefepime; Cefotaxime; Ceftazidime; Ceftriaxone; Cephalosporins; Communicable Diseases; Gentamicins; Humans; Infant, Newborn; Infant, Newborn, Diseases; Microbial Sensitivity Tests

Tropical infections form 20-30% of ICU admissions in tropical countries. Diarrheal diseases, malaria, dengue, typhoid, rickettsial diseases and leptospirosis are common causes of critical illness. Overlapping clinical features makes initial diagnosis challenging. A systematic approach involving (1) history of specific continent or country of travel, (2) exposure to specific environments (forests or farms, water sports, consumption of exotic foods), (3) incubation period, and (4) pattern of organ involvement and subtle differences in manifestations help in differential diagnosis and choice of initial empiric therapy. Fever, rash, hypotension, thrombocytopenia and mild derangement of liver function tests is seen in a majority of patients. Organ failure may lead to shock, respiratory distress, renal failure, hepatitis, coma, seizures, cardiac arrhythmias or hemorrhage. Diagnosis in some conditions is made by peripheral blood smear examination, antigen detection or detection of microbial nucleic acid by PCR. Tests that detect specific IgM antibody become positive only in the second week of illness. Initial therapy is often empiric; a combination of intravenous artesunate, ceftriaxone and either doxycycline or azithromycin would cover a majority of the treatable syndromes. Additional antiviral or antiprotozoal medications are required for some specific syndromes. Involving a physician specializing in tropical or travel medicine is helpful.

Topics: Artesunate; Azithromycin; Ceftriaxone; Child; Communicable Diseases; Critical Care; Dengue; Diagnosis, Differential; Doxycycline; Exanthema; Female; Fever; Geography; Humans; Intensive Care Units; Leptospirosis; Malaria; Male; Nervous System Diseases; Pregnancy; Shock, Hemorrhagic; Syndrome; Travel; Tropical Medicine; Typhoid Fever

Endocarditis due to Propionibacterium acnes is a rare disease. Scant data on treatment of these infections is available and is based on case reports only. If the disease is complicated by abscess formation, surgical intervention combined with an antibiotic therapy might improve clinical outcome. In some cases, cardiac surgeons are reluctant to perform surgery, since they consider the intervention as high risk. Therefore, a conservative therapy is required, with little, if any evidence to choose the optimal antibiotic. We report the first case of a successfully treated patient with P. acnes prosthetic valve endocarditis without surgery.. We report the case of a 29-year-old patient with a prosthetic valve endocarditis and composite graft infection with abscess formation of the left ventricular outflow tract due to P. acnes. Since cardiac surgery was considered as high risk, the patient was treated intravenously with ceftriaxone 2 g qd and rifampin 600 mg bid for 7 weeks and was switched to an oral therapy with levofloxacin 500 mg bid and rifampin 600 mg bid for an additional 6 months. Two sets of blood cultures collected six weeks after completion of treatment remained negative. The patient is considered to be cured based on absence of clinical signs and symptoms, normal laboratory parameters, negative radiology scans and negative blood cultures, determined at site visits over two years after completion of treatment.. To our knowledge, this is the first successfully managed patient with P. acnes prosthetic valve endocarditis with abscess formation of the left ventricular outflow tract who was treated with antibiotics alone without a surgical intervention. A six month treatment with a rifampin and levofloxacin combination was chosen, based on the excellent activity against stationary-phase and adherent bacteria.

Topics: Abscess; Adult; Anti-Bacterial Agents; Ceftriaxone; Communicable Diseases; Endocarditis, Bacterial; Gram-Positive Bacterial Infections; Heart Valve Prosthesis; Humans; Levofloxacin; Male; Middle Aged; Propionibacterium acnes; Prosthesis-Related Infections; Rifampin; Treatment Outcome