News You Can Use: Antimicrobial Stewardship

By: Jennifer Hauler, DO, vice president of medical affairs, chief medical officer of Premier Health Partners

The below table summarizes data available regarding short course antimicrobial therapy in comparison to historical treatment durations. When considering antibiotic duration, always critically evaluate patient for improvement in their condition while on antibiotics. These studies of shorter, or preferred, treatment duration consistently show equivalent efficacy. This evidence suggests that shorter duration of antibiotics may also lead to less antibiotic resistance and can shorten hospital stay.

Disease State	Preferred	Historic	Comments
Acute Bacterial Sinusitis	5 days	10 days	Most URIs are viral and should NOT be treated with antibiotics Consider antibiotics when: Symptoms of acute rhinosinusitis fail to improve ≥10 days after onset of URI Fever 102°F (39°C)
Acute bronchitis	Do not treat	Do not treat	Use of antibiotics is NOT recommended
Acute Exacerbation of Chronic Bronchitis and COPD	≤5 days	≥7 days	Reserve antibiotics for: Acute exacerbation with significant physiological compromise on top of chronic bronchitis COPD patients with physiological compromise, worsening sputum purulence, and increased dyspnea or frequency of cough
CAP	5 days	7-10 days	CAP should be treated for a minimum of 5 days Should be afebrile for 48–72 hrs Should have no more than one CAP-associated sign of clinical instability before discontinuation of therapy Longer duration of therapy may be needed if Initial therapy was not active against the identified pathogen Complicated by extrapulmonary infection, such as meningitis or endocarditis
Nosocomial Pneumonia	7 days	10-15 days	Longer duration of therapy may be needed if Response has been poor Infection is due to a non-fermenting Gram-negative bacillus such as Pseudomonas aeruginosa
Intra-abdominal infection	4 days	10 days	Limit antibiotics to 4 days after source control in patients who are hemodynamically stable. Patients who are unstable or unable to achieve source control should be discussed with ID
Uncomplicated Gram-Negative Bacteremia	7 days	14 days
Uncomplicated Staph Bacteremia	<14 days	4-6 weeks	Start counting antibiotic days after first negative blood culture
Cellulitis and skin abscesses	5-6 days	10 days
Asymptomatic Bacteriuria	0		Use of antibiotics is NOT recommended unless the patient is pregnant OR has upcoming urological procedure
Complicated UTI	5-7 days	10-14 days	For patients with anatomical abnormalities or urinary-catheter-related problems. Obtain source control first- removal of urinary catheter recommended.
Cystitis	1-5 days		5 days of nitrofurantoin 3 days of TMP-SMX 1 dose of Fosfomycin
Otitis Media		5-10 days	5 days is sufficient to treat the infection; 10-day course reduces clinical failure rate. Consider 10-day course in severe cases

CAP

• el Moussaoui R, de Borgie CA, van den Broek P, et al. Effectiveness of discontinuing antibiotic treatment after three days versus eight days in mild to moderate-severe community acquired pneumonia: randomized, double blind study. Bmj. 2006;332(7554):1355.
• Mild to moderate-severe CAP, 119 patients randomized
• Patients who substantially improved after 3 days of IV amoxicillin were randomly assigned to oral amoxicillin (n = 63) or placebo (n = 56) three times daily for five days
• In the three day and eight-day treatment groups the clinical success rate at day 10 was 93% for both (difference 0.1%, 95% confidence interval - 9% to 10%) and at day 28 was 90% compared with 88% (difference 2.0%, - 9% to 15%)
• In Netherlands, amoxicillin is preferred empiric treatment for mild to moderate-severe pneumonia
• 3 days course is not inferior to 8-day course

• Uranga A, España PP, Bilbao A, et al. Duration of Antibiotic Treatment in Community-Acquired Pneumonia: A Multicenter Randomized Clinical Trial. JAMA Intern Med. 2016;176(9):1257-65.
  • 312 patients randomized
  • Patients were assessed for eligibility from day 0 to day 5 and randomized by a researcher at day 5 to an intervention or control group. Patients in the intervention group were treated with antibiotics for a minimum of 5 days, and the antibiotic treatment was stopped at this point if their body temperature was 37.8°C or less for 48 hours and they had no more than 1 CAP-associated sign of clinical instability, defined as systolic blood pressure less than 90 mmHg, heart rate greater than100/min, respiratory rate greater than 24 /min, arterial oxygen saturation less than 90%, or PaO2 less than 60mmHg in roomair. In contrast, duration of antibiotics in the control group was determined by physicians as in clinical practice
  • Inclusion: Hospitalized patients diagnosed with CAP and 18 years and older
  • Exclusion: HIV patients, chronic immunosuppression, lived in nursing home, had been discharged from acute care hospital, subacute care unit, or palliative care in the last 14 days, had already taken antibiotics in the last 30 days before admission, required longer duration of therapy because of uncommon cause (Pseudomonas aeruginosa or Staphylococcus aureus); required chest tube; or had condition complicated by extrapulmonary infection (endocarditis or meningitis)
  • This study indicates that withdrawing antibiotic treatment based on clinical stability criteria after a minimum of 5 days of appropriate treatment is not inferior to traditional treatment schedules in terms of clinical success
  • Clinical cure rates at late follow-up were 92.7% and 94.4% in the control and intervention groups, respectively

• Pereira JM, Gonçalves-pereira J, Ribeiro O, Baptista JP, Froes F, Paiva JA. Impact of antibiotic therapy in severe community-acquired pneumonia: Data from the Infauci study. J Crit Care. 2018;43:183-189.
  • 502 patients with severe CAP
  • Most of the patients (n= 381; 76%) received combination antibiotic therapy, mainly a β-lactam plus a macrolide (80%)
  • Hospital mortality was similar in patients treated with antibiotic monotherapy or with combination therapy (37% vs. 33%;p=0.43), it was significantly lower when a combination therapy including β-lactam and a macrolide was used (27% vs. 58% for all other antibiotic regimens; p<0.001)
  • Duration of appropriate antibiotic therapy not longer than 7 days was not associated with a worst outcome nor increased ICU or hospital LOS

• Shaddock EJ, Feldman C. Shorter antibiotic courses in community-acquired pneumonia-ready for prime time. J Thorac Dis. 2016;8(12):E1628-E1631.
• CAP should be treated for a minimum of 5 days
• Should be afebrile for 48–72 hrs
• Should have no more than one CAP-associated sign of clinical instability before discontinuation of therapy
• Longer duration of therapy may be needed if
• Initial therapy was not active against the identified pathogen
• complicated by extrapulmonary infection, such as meningitis or endocarditis

Nosocomial Pneumonia

• Halm EA, Fine MJ, Marrie TJ, et al. Time to clinical stability in patients hospitalized with community-acquired pneumonia: implications for practice guidelines. JAMA. 1998;279(18):1452-7.
  • 648 patients in this trial
  • Inclusion: 18 years or older, symptoms suggestive of acute pneumonia, radiographic evidence of pneumonia
  • Exclusion: HIV patients and patients who have been hospitalized within 10 days were excluded
  • Patients who were transitioned to ICU, CCU or telemetry monitoring units were classified into Special Care Unit group
  • Time to overall stability differed by definition:
  • Temp <38.3C, HR <100, SBP >90, RR<24, O2 stat >90: duration to clinical stability was 3 days
  • More conservative vital sign criteria: duration of therapy took 5-7 days
  • Among these 648 patients, the median day of discontinuing parenteral therapy was day 6

• Frantzeskaki F, Orfanos SE. Treating nosocomial pneumonia: what's new. ERJ Open Res. 2018;4(2)
  • Recommend a 7–8-day course of antibiotics, in the absence of pulmonary empyema, lung abscess, cavitation and necrotizing pneumonia

• Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005;171(4):388-416.
  • A shorter duration of antibiotic therapy (7 to 8 days) is recommended for patients with uncomplicated HAP, VAP, or HCAP who have received initially appropriate therapy and have had a good clinical response, with no evidence of infection with nonfermenting gram-negative bacilli

• Chastre J, Wolff M, Fagon JY, et al. Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA. 2003;290(19):2588-98.
  • 401 ICU patients, study from France
  • Inclusion: 18 years or older; clinical suspicion of VAP; positive quantitative cultures of distal pulmonary secretion samples; and correctly initiated empiric therapy within 24 hours
  • Exclusion: pregnancy; enrolled in another trial; had little chance of survival; ha neutropenia; had AIDS; immunosuppressed; had concomitant extrapulmonary infection; or their attending physician declined to use full life support
  • Microbiologically documented pulmonary infection recurrence rate was 28.9% of patients receiving the eight day regimen and 26% of those taking antibiotics for 15 days with absolute difference of 2.9% (90%CI, -3.2% to 9.1%)

• Pugh R, Grant C, Cooke RP, Dempsey G. Short-course versus prolonged-course antibiotic therapy for hospital-acquired pneumonia in critically ill adults. Cochrane Database Syst Rev. 2015;(8):CD007577.

Intra-abdominal infection

• Trial of Short-Course Antimicrobial Therapy for Intraabdominal Infection. N Engl J Med. 2018;378(7):686.
  • 517 patients in this trial
  • In patients with intraabdominal infections who had undergone an adequate source-control procedure, the outcomes after fixed-duration antibiotic therapy (approximately 4 days) were similar to those after a longer course of antibiotics (approximately 8 days) that extended until after the resolution of physiological abnormalities
  • With adequate source control, a shorter course of 3 to 5 days should suffice for cure
  • Surgical Infection Society (SIS) and the Infectious Diseases Society of America (IDSA), recommend a treatment course of 4 to 7 days, depending on the clinical response

• Smith SE, Rumbaugh KA, May AK. Evaluation of a Short Course of Antimicrobial Therapy for Complicated Intra-Abdominal Infections in Critically Ill Surgical Patients. Surg Infect (Larchmt). 2017;18(6):742-750.
  • Single-center, retrospective, cohort study at Vanderbilt University Medical Center (VUMC)
  • Patient population: surgical ICU; 240 patients
  • Inclusion: 18 y of age or older, were admitted to the SICU for at least 24 h, received appropriate empiric antimicrobial treatment per the SIS/IDSA guidelines, and underwent an intervention to achieve source control
  • Exclusion: Pregnant patients, those undergoing solid organ transplantation, and patients with multiple admissions to the SICU during the specified time period
  • Patients in the short and long groups received a median of 5 and 14 d of therapy
  • Treatment failure occurred less frequently with a short duration of therapy (39% versus 63%, p < 0.001) and it occurred two days sooner after source control in patients receiving the shorter courses of antimicrobial therapy (short, median 6 d, interquartile range [IQR] 3–9; long, 8 d, IQR 6–14; p < 0.001)

• Kim IK, Lee JG. Antibiotic duration can be shortened in postoperative intra-abdominal infection. J Thorac Dis. 2018;10(Suppl 26):S3182-S3183
  • Study suggested that the number of antibiotic-free days was higher in the 8-day arm (15 days in the 8-day arm vs. 12 days in the 15-day arm, P<0.0001) corresponding on a 15% relative reduction in antibiotic exposure. However, the 45-day mortality rates and length of ICU stay did not differ between the two groups. Moreover, it did not detect any difference in the rates of emergence of multi-drug resistant bacteria except for Pseudomonas aeruginosa between the two groups

Acute Exacerbation of Bronchitis and COPD

• El moussaoui R, Roede BM, Speelman P, Bresser P, Prins JM, Bossuyt PM. Short-course antibiotic treatment in acute exacerbations of chronic bronchitis and COPD: a meta-analysis of double-blind studies. Thorax. 2008;63(5):415-22.
  • In this systematic review of randomized double-blind studies, it was found that a short course of antibiotic treatment is as effective as the traditional longer treatment in patients with mild to moderate exacerbations of chronic bronchitis and COPD.

Acute Bacterial Sinusitis

• Elies W, Huber K. Short-course therapy for acute sinusitis: how long is enough?. Treat Respir Med. 2004;3(5):269-77.
  • The evidence reviewed in this article strongly supports reduction of the traditional 10-day course of antibacterial therapy to a 5-day course for uncomplicated acute maxillary sinusitis in adults
  • Open, randomized, comparative, parallel group study at 26 centers in Germany
  • Cefuroxime axetil (2 x 250 mg BID) for 5 days v 10-day treatment with clarithromycin 500 mg BID
  • 301 patients in this study
  • Inclusion: age between 18 and 80, spontaneous pain and/or pain on pressure over affected paranasal sinus, nasal congestion, purulent nasal secretion
  • Clinical success with cefuroxime axetil was 95.9% and was found to be equivalent to 10-day therapy with clarithromycin
  • Cure was achieved in 87.6% patients treate with cefuroxime axetil and with clarithromycin was 69.9%

• Falagas ME, Karageorgopoulos DE, Grammatikos AP, Matthaiou DK. Effectiveness and safety of short vs. long duration of antibiotic therapy for acute bacterial sinusitis: a meta-analysis of randomized trials. Br J Clin Pharmacol. 2009;67(2):161-71.
  • There was no difference in the comparison of short-course (3–7 days) with long-course treatment (6–10 days) regarding clinical success
  • Acute bacterial sinusitis was defined by the presence of a constellation of characteristic clinical manifestations, including, among others, nasal congestion or obstruction, purulent rhinorrhea, post nasal drip, facial pain or toothache, tenderness over the affected area, cough, fever, and halitosis,

Cellulitis

• Cranendonk DR, Opmeer BC, Prins JM, Wiersinga WJ. Comparing short to standard duration of antibiotic therapy for patients hospitalized with cellulitis (DANCE): study protocol for a randomized controlled trial. BMC Infect Dis. 2014;14:235.
  • Dutch guidelines recommended using flucloxacillin for patients with cellulitis
  • Inclusion: 18 years or older and admitted receiving IV antibiotics for cellulitis/erysipelas
  • Exclusion: allergy to flucloxacillin or other B lactam antibiotics; concurrent use of antibiotics for other indications; alternative diagnosis accounting for clinical presentation; ICU admission in last 7 days; severe PAD; severe cellulitis necessitating surgical debridement or fascial biopsy; necrotizing fasciitis; periorbital or perirectal involvement; surgery; life expectancy less than one month; risk factors associated with Gram-negative
  • https://clinicaltrials.gov/ct2/show/study/NCT02032654

Complicated UTI

• Nicolle LE. Short-term therapy for urinary tract infection: success and failure. Int J Antimicrob Agents. 2008;31 Suppl 1:S40-5.
• Ren H, Li X, Ni ZH, et al. Treatment of complicated urinary tract infection and acute pyelonephritis by short-course intravenous levofloxacin (750 mg/day) or conventional intravenous/oral levofloxacin (500 mg/day): prospective, open-label, randomized, controlled, multicenter, non-inferiority clinical trial. Int Urol Nephrol. 2017;49(3):499-507.
  • Inclusion: 18 years or older, had diagnosis of complicated UTI or acute pyelonephritis (females only), and were willing to participate in the study
  • Exclusion: pregnant, breast feeding, received other systemic antimicrobial therapy due to UTI, required or received long-lasting indwelling catheter, had complete urinary tract obstruction, had urinary tract tumors, received urinary tract surgery or lithotripsy in 7 days before study, had history of epilepsy, had history of quinolone-induced tendon lesions, had history of prolonged QT interval, were allergic to levofloxacin or other quinolones, received any antibiotic therapy within 72 hours before study onset and if their condition improved within 72 hours before study onset, had severe heart disease, liver disease or pre-existing kidney disease, received therapy with at least one drug use in this study in the 4 weeks before study onset, had at least one health-threatening clinical disease or abnormality that could affect quality of data
  • Intention-to-treat analysis indicated the clinical effectiveness in the short-course therapy group (89.87%, 142/158) was non-inferior to that in the conventional therapy group (89.31%, 142/159). The microbiological effectiveness rates were also similar (short-course therapy: 89.55%, 60/67; conventional therapy: 86.30%, 63/73; p > 0.05)

Cystitis

• Jancel T, Dudas V. Management of uncomplicated urinary tract infections. West J Med. 2002;176(1):51-5.
  • Controlled trials of uncomplicated urinary tract infections have demonstrated that therapy for 3 days provided similar eradication rates and a lower incidence of side effects compared with 7 to 10 days of therapy
  • 1999 treatment guidelines of the Infectious Disease Society of America on uncomplicated urinary tract infections concluded that multiple-day regimens were more effective than single-dose regimens, especially for the aminopenicillins and first-generation cephalosporins
  • third generation cephalosporins such as cefixime and cefpodoxime offer the advantage of longer half-lives, which allows for less frequent dosing

• Rosenberg JM, Levy RC, Cicmanec JF, Hedges JR, Burke BM. Single-dose ceftriaxone treatment of urinary tract infections. Ann Emerg Med. 1985;14(10):970-2.
  • 52 patients in the trial
  • Single dose of ceftriaxone 500 mg IM (reconstituted in 1% lidocaine) v 5 day course of TMX/SMX 800/200 mg Q12H
  • Inclusion: female patients with initial laboratory and clinical symptoms suggestive of UTI
  • Exclusion: prior antibiotics, allergies to sulfa trimethoprim, penicillin, or cephalosporins; pregnancy, medical complications (diabetes), history of frequent UTI, urethral strictures, catherization or other instrumentation, less than 18 years of age
  • 13/13 patients in TMX/SMX group were cured
  • 18/20 patients in ceftriaxone group were cured
  • 1 patient had organism resistant to ceftriaxone
  • 1 patient had slowly abating symptoms ad was transitioned to another antibiotic

• Sanchez M, Collvinent B, Miró O, et al. Short-term effectiveness of ceftriaxone single dose in the initial treatment of acute uncomplicated pyelonephritis in women. A randomised controlled trial. Emerg Med J. 2002;19(1):19-22.
  • open, prospective, and randomized trial of women with acute uncomplicated pyelonephritis
  • daily dose of ceftriaxone 1 g IV v ceftriaxone 1 g iv single dose followed by oral cefixime
  • Inclusion: women between 18 and 75 years, presumptive diagnosis of uncomplicated acute pyelonephritis based on temperature >38C, urinary syndrome, flank pain, and pyuria
  • Exclusion: pregnancy or nursing, presence of urinary catheter, antibiotic treatment in preceding seven days, renal transplant, UTI in preceding 30 days, known functional or structural abnormality of urinary tract, and known hypersensitivity to cephalosporins
  • clinical response after the three-day treatment was not significantly different between both groups.
  • clinical cure was observed in 49 of 54 (91%) patients in the group A and in 47 of 51 (92%) patients in the group B (p = 0.68)

Asymptomatic bacteriuria

• Sabé N, Oriol I, Melilli E, et al. Antibiotic Treatment Versus No Treatment for Asymptomatic Bacteriuria in Kidney Transplant Recipients: A Multicenter Randomized Trial. Open Forum Infect Dis. 2019;6(6):ofz243.
  • This is multicenter, open label, nonblinded, prospective, noninferiority, randomized controlled trial in patients with kidney transplant
  • 205 patients enrolled in trial
  • Inclusion: 18 years or older and had received kidney transplant in previous month
  • Exclusion: participation in another trial, graft loss, patients with surgical complications that required prolonged need for urinary catheters
  • Antibiotic treatment of asymptomatic bacteriuria was not useful to prevent acute graft pyelonephritis in kidney transplant recipients and may increase antibiotic resistance.

• Lindsay E Nicolle, Kalpana Gupta, Suzanne F Bradley, Richard Colgan, Gregory P DeMuri, Dimitri Drekonja, Linda O Eckert, Suzanne E Geerlings, Béla Köves, Thomas M Hooton, Manisha Juthani-Mehta, Shandra L Knight, Sanjay Saint, Anthony J Schaeffer, Barbara Trautner, Bjorn Wullt, Reed Siemieniuk, Clinical Practice Guideline for the Management of Asymptomatic Bacteriuria: 2019 Update by the Infectious Diseases Society of America, Clinical Infectious Diseases, Volume 68, Issue 10, 15 May 2019, Pages e83–e110, https://doi.org/10.1093/cid/ciy1121 
  • IDSA recommends against screening and treating healthy premenopausal, nonpregnant women or healthy postmenopausal women, older residents of LTCF, patients who received solid organ transplant, and patients with diabetes.

Otitis media

• Kozyrskyj A, Klassen TP, Moffatt M, Harvey K. Short-course antibiotics for acute otitis media. Cochrane Database Syst Rev. 2010;(9):CD001095.
  • This update included 49 trials containing 12,045 participants. Risk of treatment failure was higher with short courses of antibiotics (OR 1.34, 95% CI 1.15 to 1.55) at one month after initiation of therapy (21% failure with short-course treatment and 18% with long-course; absolute difference of 3% between groups)

• Hoberman A, Paradise JL, Rockette HE, et al. Shortened Antimicrobial Treatment for Acute Otitis Media in Young Children. N Engl J Med. 2016;375(25):2446-2456.
  • Inclusion: Children, 6 to 23 months of age, received at least two doses of pneumococcal conjugate vaccine and have acute otitis media that was diagnosed
  • Exclusion: Children who had tympanic-membrane perforation or another illness, who were allergic to amoxicillin, or who had received more than one dose of an antimicrobial agent within the previous 96 hours
  • Children who were treated with amoxicillin–clavulanate for 5 days were more likely than those who were treated for 10 days to have clinical failure (77 of 229 children [34%] vs. 39 of 238 [16%]; difference, 17 percentage points [based on unrounded data]; 95% confidence interval, 9 to 25)

Uncomplicated Staph Bacteremia

• Chong YP, Moon SM, Bang KM, et al. Treatment duration for uncomplicated Staphylococcus aureus bacteremia to prevent relapse: analysis of a prospective observational cohort study. Antimicrob Agents Chemother. 2013;57(3):1150-6.
  • Prospective observational cohort study in patients with Staph Aureus bacteremia in Korea
  • 111 patients met criteria for uncomplicated Staph Aureus bacteremia
  • 53/111 (47.7%) had MRSA
  • When short-course therapy (<14 days) and intermediate-course therapy (≥14 days) were compared, the treatment failure rates (10/38 [26.3%] versus 16/73 [21.9%]) and crude mortality (7/38 [18.4%] versus 16/73 [21.9%]) did not differ significantly between the two groups. However, short-course therapy was significantly associated with relapse (3/38 [7.9%] versus 0/73; P = 0.036)

• Holland TL, Arnold C, Fowler VG. Clinical management of Staphylococcus aureus bacteremia: a review. JAMA. 2014;312(13):1330-41
  • In 9 studies with a total of 3513 patients, use of TEE was associated with higher rates of diagnosis of endocarditis (14–25%) when compared with TTE (2–14%)
  • MRSA treatment guidelines define uncomplicated SAB as infection in which: a) endocarditis has been excluded; b) no implanted prostheses are present; c) follow-up blood cultures drawn 2–4 days after the initial set are sterile; d) the patient defervesces within 72 hours of initiation of effective antibiotic therapy; and e) no evidence of metastatic infection is present on exam. Treat for at least 14 days from the first negative blood culture

Gram Negative Bacteremia

• Yahav D, Franceschini E, Koppel F, et al. Seven versus fourteen Days of Antibiotic Therapy for uncomplicated Gram-negative Bacteremia: a Non-inferiority Randomized Controlled Trial. Clin Infect Dis. 2018;
• Randomized, multicenter, open-label, non-inferiority trial
• 604 patients from Italy and Israel
• Inclusion: hospitalized adult patients with aerobic Gram-negative bacteremia, patients with urinary tract, intra-abdominal, respiratory tract, central venous catheter, or skin and soft tissue infection or an unknown source of bacteremia
• Exclusion: uncontrolled focus of infection, polymicrobial growth, specific pathogens (Brucella, Salmonella), or immunosuppression (neutropenia at time of randomization, human immunodeficiency virus, recent allogeneic stem cell transplantation)
• The source of the infection was urinary in 411/604 (68%); causative pathogens were mainly Enterobacteriaceae (543/604, 90%)
• Primary outcome at 90 days was a composite of all-cause mortality and it occurred in 140/306 (45.8%) patients in the 7 days group versus 144/298 (48.3%) in the 14 days group (risk difference [RD] -2.6%, 95% confidence interval [CI] -10.5% to 5.3%)

• Swamy S, Sharma R. Duration of Treatment of Gram-Negative Bacteremia. Infectious Diseases in Clinical Practice. 2016;24(3):155-160. doi:10.1097/ipc.0000000000000362.
  • Single-center, retrospective, case-cohort study
  • 178 patients randomized
  • Inclusion: 18 years or older and documented Gram-negative bacteremia
  • Exclusion: pregnant, had altered immunocompetence (human immunodeficiency virus infection, graft transplantation, neutropenia [absolute neutrophil count <500 cells], and use of immunosuppressive medications), mixed growth in blood cultures (growth of both Gram-positive, Gram-negative, or fungal organisms in either the same blood culture or 2 or more separated blood cultures), a complicated infection (endocarditis, osteomyelitis, necrotizing fasciitis, uncontrolled abscess [not drained properly or unable to drain], central nervous system infection, central venous catheter infection when the infected catheter is not removed
  • The most common infecting pathogen was E. coli (48% of isolates), followed by K. pneumoniae (21% of isolates). Fewer than 20% of bacteremias were caused by non–lactose-fermenting Gram-negative organisms
  • The subgroup analysis of patients who defervesce after 72 hours indicated a significantly increased likelihood of a lack of clinical response at the end of therapy in the short-course treatment group

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