Oral antibiotics noninferior to IV antibiotics for K. pneumoniae liver abscess

Adults hospitalized for liver abscess due to Klebsiella pneumoniae (K. pneumoniae) could be treated with oral rather than intravenous (IV) antibiotics, according to a trial from Singapore.

“[A]mong patients with K. pneumoniae liver abscess, stepdown to oral antibiotics after 5 days of effective IV antibiotics resulted in a noninferior rate of clinical cure at 12 weeks compared with continuing IV antibiotics,” said the researchers.

The study, conducted at three sites in Singapore, involved 152 adults (mean age 58.7 years, 25.7 percent female) hospitalized for K. pneumoniae liver abscess (in blood or abscess fluid) who had been treated with IV antibiotics for up to 7 days (median 5 days). They were randomized to receive oral ciprofloxacin (n=74; 750 mg for body weight ≥75 kg or 500 mg for <75 kg BID) or IV ceftriaxone (n=78; 2 g/day) for 28 days. Additional oral antibiotic treatment was administered for those who failed to meet a clinical response at 28 days. Bacteraemia was present in a similar proportion of oral and IV antibiotic recipients (85.1 percent vs 82.0 percent). About 70 percent of patients (n=106) underwent abscess drainage. Patients in both groups were treated for a median 29 days, inclusive of additional treatment.

At week 12, the use of oral antibiotics was noninferior to IV antibiotics in terms of the proportion of patients with clinical cure, defined as C-reactive protein <20 mg/L, temperature <38°C at week 12 and in the preceding week, and reduced maximal diameter of the abscess (95.9 percent vs 92.3 percent; risk difference [RD], 3.6 percent, 95 percent confidence interval [CI], -4.9* to 12.8 percent; p=0.001). [Clin Infect Dis 2019;doi:10.1093/cid/ciz881]

A greater proportion of patients receiving oral rather than IV antibiotics achieved clinical response at week 4 (same criteria as clinical cure but at 4 weeks; 90.5 percent vs 79.5 percent; RD, 11.1 percent, 95 percent CI, -0.7 to 23.0 percent; p<0.001), all of whom had clinical cure at 12 weeks.

“[These findings] support the use of shorter oral [antibiotic] courses,” said the researchers.  

A comparable number of patients on oral and IV antibiotics did not meet clinical response at 28 days (n=30 vs 33) and received additional antibiotic treatment. Unplanned hospital readmissions (16.2 percent vs 10.3 percent; p=0.34), new K. pneumoniae bacteraemia (1.4 percent vs 0; p=0.49), and treatment adherence (93.2 percent vs 97.4 percent; p=0.27) also did not significantly differ between groups. There was also no between-group difference in the incidence of metastatic complications (p=0.71). However, patients on IV antibiotics had a longer duration of hospitalization than those on oral antibiotics (median 6 vs 4 days; p=0.03).

Nonfatal serious adverse events affected a similar proportion of oral and IV antibiotic recipients (16.7 percent vs 16.9 percent). There were no deaths in either group. Drug discontinuations due to toxicity did not significantly differ between oral and IV antibiotic recipients (2.8 percent vs 1.3 percent; p=0.61) nor did treatment cessation due to worsening or secondary infection (6.9 percent vs 2.6 percent; p=0.26).

“Administration of prolonged courses of IV antibiotics is resource-intensive and risks intravascular device-related complications,” said the researchers. “Our findings [support] the use of highly bioavailable oral antibiotics for indications formerly considered the role of IV antibiotics,” they said.