Expired amoxicillin

8 Recent infectious disease “Choosing Wisely” initiatives recommend clinicians “prefer oral formulations of highly bioavailable antimicrobials whenever possible”, 9 and this approach is supported by the Centers for Disease Control and Prevention antibiotic stewardship program. 10 However, the expected savings and benefits of oral therapy would be lost should they be less effective and result in treatment failure or relapse of the primary BSI. Pathogen susceptibility, gastrointestinal absorption, oral bioavailability, patient tolerability, and adherence with therapy need to be carefully considered before choosing oral antimicrobials.

Thus, oral antimicrobial therapy for BSI should be utilized in carefully selected circumstances.

In this narrative review, we highlight areas where oral therapy is safe and effective in treating bloodstream infections, as well as offer guidance to clinicians managing patients experiencing BSI. Given the lack of robust clinical trials on this subject, the evidence for performing a systematic review was insufficient. Thus, the articles and recommendations cited in this review were selected based on the authors’ experiences to represent the best available evidence. Evidence Regarding Bloodstream Infections due to Gram-Negative Rods.

BSIs due to gram-negative rods (GNRs) are common and cause significant morbidity and mortality.

GNRs represent a broad

and

The Enterobacteriaceae family includes Escherichia coli, Klebsiella, Salmonella, Proteus, Enterobacter, Serratia, and Citrobacter species. The range of illnesses caused by Enterobacteriaceae is as diverse as the family, encompassing most

body

However, Enterobacteriaceae species susceptible to oral antimicrobials are often suitable candidates for oral BSI therapy. Among 106 patients with GNR BSI treated with a highly bioavailable oral antibiotic (eg, levofloxacin), the treatment failure rate was only 2% (versus 14% when an antimicrobial with only moderate or low bioavailability was selected). 15 Oral treatment of Enterobacteriaceae amoxicillin 500 tablet BSIs secondary to urinary tract infection has been best studied. A prospective randomized, controlled trial evaluated oral versus intravenous ciprofloxacin amongst 141 patients with severe pyelonephritis or complicated urinary tract infections, in which the rate of bacteremia was 38%. 16 Notably, patients with obstruction or renal abscess were excluded from the trial.

No significant differences in microbiological failure or unsatisfactory clinical responses were found between the IV and oral treatment groups.

Additionally, a Cochrane review reported that oral antibiotic therapy is no less effective than intravenous therapy for severe UTI, although data on BSI frequency were not provided. Resistance to fluoroquinolones such as ciprofloxacin has been identified as a risk factor for GNR BSI oral treatment failure, highlighting the importance of confirming susceptibilities before committing to an oral treatment plan. 18,19 Even ESBL Enterobacteriaceae can be considered for treatment with fluoroquinolones if susceptibilities allow. The ideal duration of therapy for GNR BSI is an area of active research. A recent retrospective trial showed no difference in all-cause mortality or recurrent BSI in GNR BSI treated for 8 versus 15 days.

21 A recent meta-analysis suggested that 7 days of therapy was noninferior to a longer duration therapy (10–14 days) for pyelonephritis, in which a subset was bacteremic. 22 However, another trial reported that short course therapy for GNR BSI ( 22 Further data are needed. Pseudomonas aeruginosa is a common pathogen, intrinsically resistant to many antimicrobials, and readily develops antimicrobial resistance during therapy. Fluoroquinolones (such as ciprofloxacin, levofloxacin, and delafloxacin) are the only currently available oral agents with antipseudomonal activity. However, fluoroquinolones may not achieve blood concentrations appropriate for P. aeruginosa treatment at standard doses, while higher dose regimens may be associated with increased risk for undesirable side effects.

24,25 Currently, given the minimal trial data comparing oral versus intravenous therapy for P. aeruginosa BSIs, and multiple studies indicating increased mortality when P. aeruginosa is treated inappropriately, 26,27 we prefer a conservative approach and consider oral therapy a less-preferred option. Evidence Regarding Bloodstream Infections due to Gram-Positive Cocci. The majority of bloodstream infections in the United States, and the resultant morbidity and mortality, are from gram-positive cocci (GPCs) such as Staphylococcus, Streptococcus, and Enterococcus species. pneumoniae infection in the United States, approximately 40,000 are complicated by BSI, with 70% of those cases being secondary to pneumococcal pneumonia.

28 In studies on patients with pneumococcal pneumonia, bacteremic cases generally fare worse than those without bacteremia.

29,30 However, several trials demonstrated comparable outcomes in the setting of bacteremic pneumococcal pneumonia when switched early (within 3 days) from intravenous to oral antibiotics to complete a 7-day course. 31,32 Before pneumococcal penicillin amoxicillin effectiveness resistance became widespread, oral penicillin

was

This observation highlights the importance of knowing the final susceptibility data prior to consolidating to monotherapy with an

oral

Although the evidence for treating bacteremic pneumococcal pneumonia using a highly active and absorbable oral agent is fairly robust, S.

pneumoniae BSI secondary to other sites of infection sites is less well studied and may require a more conservative approach.

Gram-Positive Cocci, ? -hemolytic Streptococcus species. ?-Hemolytic Streptococci include

groups

agalactiae) are the most commonly implicated in BSIs. 36 Group A Streptococcus (GAS) is classically associated with streptococcal pharyngitis and Group B Streptococcus (GBS) is associated with postpartum endometritis and neonatal meningitis, though both are virulent organisms with a potential to cause invasive infection throughout the body and in all age-groups. Up to 14% of will amoxicillin treat flu GAS and 41% GBS BSIs have no clear source; 37,38 given these are skin pathogens, such scenarios likely represent invasion via microabrasion.

As ?-hemolytic streptococcal BSI is often observed in the context of necrotizing skin and soft tissue infections, surgical source control is particularly important.

39 GAS remains exquisitely susceptible to penicillin, and intravenous penicillin remains the mainstay for invasive disease; GBS has higher penicillin resistance rates than GAS.

40 Clindamycin should be added when there is concern for severe disease or toxic shock. 41 Unfortunately, oral penicillin is poorly bioavailable (approximately 50%), and there has been recent concern regarding inducible clindamycin resistance in GAS.

42 Thus, oral penicillin V and/or clindamycin is a potentially risky strategy, with no clinical trials supporting this approach; however, they may be reasonable options in selected patients with source control and stable hemodynamics.

Amoxicillin has high bioavailability (85%) and may be effective; however, there is lack of supporting data.

Highly bioavailable agents such as

levofloxacin

Because no clinical trials have compared these

agents

Although bacteriostatic against Staphylococcus, linezolid is bactericidal against Streptococcus.

44 Fluoroquinolone resistance amongst ?-hemolytic Streptococcus is rare (approximately 0.5%) but does occur. aureus (including methicillin susceptible and resistant strains: MSSA and MRSA, respectively) and coagulase-negative species, which include organisms such as S. aureus is

the

47 The guidelines of the Infectious Diseases Society of America for the treatment of MRSA recommend the use of parenteral agents for BSI. 48 It is important to consider if a patient with S.

Although trimethoprim-sulfamethoxazole (TMP-SMX) has favorable pharmacokinetics and case series of using it successfully for BSI exist, 49 TMP-SMX showed inferior outcomes in a randomized trial comparing oral TMP-SMX with intravenous vancomycin in a series of 101 S.

aureus BSI are limited, and IDSA guidelines advise against their use in this setting because they are predominantly bacteriostatic. 48 Linezolid has favorable pharmacokinetics, with approximately 100% bioavailability, and S.

52 Several randomized trials

have

53 A pooled analysis showed oral linezolid was noninferior to vancomycin specifically for S. 54 However, long-term use is often limited by hematologic toxicity, peripheral or optic neuropathy (which can be permanent), and induced serotonin syndrome.

Additionally, linezolid is bacteriostatic, not bactericidal against S.

aureus BSI would not be recommended; however, it may be used as a second-line treatment option in selected cases.

Tedizolid has similar pharmacokinetics and spectrum of activity with fewer side effects; however, clinical data on its use for S. 55 Fluoroquinolones such as levofloxacin and the newer agent delafloxacin have activity against S. aureus, including MRSA, but on-treatment emergence of fluoroquinolone resistance is a concern, and data on delafloxacin for BSI are lacking. 56,57 Older literature suggested the combination of ciprofloxacin and rifampin was effective against right-sided S. aureus endocarditis, 58 and other oral fluoroquinolone-rifamycin combinations have also been found to be effective 59 However, this approach is currently not a standard therapy, nor is it widely used.

aureus BSI should be made in conjunction with an infectious diseases specialist; 14 days is currently

regarded

Published data regarding oral treatment of coagulase-negative Staphylococcus (CoNS) BSI are limited.

Most CoNS bacteremia and up to 80% Staphylococcus epidermidis bacteremia represent blood culture contamination, though true infection from CoNS is not uncommon, particularly in patients with indwelling catheters.

60 An exception is the CoNS species Staphylococcus lugdunensis, which is more virulent, and bacteremia with this organism usually warrants antibiotics.

Oral antimicrobial therapy is currently not a standard treatment practice for CoNS BSI that is felt to represent true infection; however, linezolid has been successfully used in case series. aureus, infective endocarditis must be ruled out when treating enterococcus BSI; a scoring system has been proposed to assist in deciding if such patients require echocardiography.

62 Intravenous ampicillin is a preferred, highly effective agent for enterococci treatment when the organism is susceptible.

44 However, oral ampicillin has poor bioavailability (50%), and data for its use in BSI are lacking.

For susceptible strains, amoxicillin has comparable efficacy for enterococci and enhanced bioavailability (85%); high dose oral amoxicillin could be considered, but amoxicillin and metronidazole there is minimal clinical trial data to support this approach.

Fluoroquinolones exhibit only modest activity against enterococci and would be an inferior choice for BSI.

63 Although often sensitive to oral tetracyclines, data on their use in enterococcal BSI are

insufficient

Nitrofurantoin can be used for susceptible enterococcal urinary tract infection; however, amoxicillin dental it does not achieve high blood concentrations and should not be used for BSI. There is

significant