Professor Yi-Tsung Lin
Professor of Institute of Emergency and Critical Care Medicine,
National Yang Ming Chiao Tung University;
Attending Physician, Division of Infectious Disease,
Department of Medicine, Taipei Veterans General Hospital,
Taiwan

Klebsiella pneumoniae is a major causative pathogen of urinary tract infection, pneumonia, and intra-abdominal infections worldwide.¹ K. pneumoniae has also recently emerged as a common cause of Klebsiella pneumoniae liver abscess (KPLA), especially in East Asian countries including Taiwan, Korea, and Singapore.² Professor Yi-Tsung Lin discussed the benefits of fluoroquinolones as alternative treatment for KPLA.

Q1. Please describe the prevalence, aetiology, and epidemiology of KPLA in Taiwan.

Most cases of KPLA reported in Taiwan are community-acquired. Community-acquired KPLA has been frequently reported in East Asian such as Korea, Singapore, and China but less commonly reported in Western countries.³ Taiwan has the highest prevalence of KPLA worldwide³ and I have published many studies on KPLA.

Q2. What are the clinical manifestations and risk factors for KPLA?

The clinical manifestations of KPLA are similar to those of pyogenic liver abscesses caused by other aetiologic agents. Symptoms of KPLA include fever, malaise, and abdominal pain. However, some patients with KPLA may have concurrent metastatic infection in other body sites. The most common manifestations of metastatic infection are endophthalmitis, meningitis and brain abscess. Other manifestations such as spondylitis and discitis, septic pulmonary emboli, lung abscess, psoas abscess, splenic abscess, necrotising fasciitis, neck abscess, and osteomyelitis have also been reported.⁴ Risk factors for pyogenic liver abscess include diabetes mellitus, liver cirrhosis, underlying hepatobiliary or pancreatic disease, liver transplant, and regular use of proton-pump inhibitors. Diabetes is the most established risk factor for KPLA. However, the study from my group also found that more than half the patients with KPLA did not have diabetes in Taiwan.¹ Liver cirrhosis and alcoholism are also risk factors for Klebsiella pneumoniae infections. We have also found that ampicillin or amoxicillin therapy within the prior 30 days was associated with KPLA.⁵

 Q3. What is the recommended treatment regimen for patients with KPLA?

There are no randomised controlled trials evaluating antibiotic regimens for the treatment of pyogenic liver abscess. Empiric broad-spectrum antibiotics covering streptococci, enteric Gram-negative bacilli, and anaerobes are commonly administered pending the microbiologic analysis of the abscess. A third-generation cephalosporin (e.g., ceftriaxone) plus metronidazole are commonly used.^2,4 In KPLA, hypervirulent K. pneumoniae strains are usually susceptible to various antibiotics except intrinsically resistant to ampicillin. In my recent study, we reported only 13 hypervirulent strains with multi-drug resistant phenotypes were identified from a total of 218 KPLA episodes in a 5-year period.⁶ In the literature, antibiotic regimens for KPLA have included extended spectrum beta-lactams and cephalosporins with or without aminoglycosides.^2,4 Anaerobic coverage is unnecessary for KPLA but metronidazole is commonly used in Korea.⁷ First generation cephalosporin has also been recommended by some experts in Taiwan.⁸

Q4. What is the role of fluoroquinolones in the treatment of patients with KPLA?

The high bioavailability of oral fluoroquinolones can potentially reduce the duration of intravenous (IV) antibiotic therapy in infectious diseases, but studies on fluoroquinolone use in KPLA are limited. One retrospective study conducted in a tertiary centre in Korea showed a median duration of IV antibiotic therapy of 17 days in patients treated with ciprofloxacin-based therapy, which was relatively shorter than those of previous studies.⁹ A recent randomised controlled study in Singapore demonstrated that step-down therapy to oral ciprofloxacin after 5 days of effective IV antibiotics resulted in a non-inferior rate of clinical cure compared with continuing intravenous ceftriaxone in KPLA cases.¹⁰ Our recent study of 234 patients with KPLA demonstrated that most patients received β-lactams (n = 199; 85.0%), whilst only 35 (15.0%) received fluoroquinolones as the major therapy. Fluoroquinolones have shown similar clinical efficacy to β-lactams even in critically ill patients. Patients treated with fluoroquinolones had a shorter intravenous antibiotics duration (18.9 ±7.6 days vs. 28.5 ±14.7 days; P <0.001) and hospital length of stay (LOS) (20.9 ±8.3 days vs. 29.5 ±16.2 days; P <0.001) than patients treated with β-lactams. We further showed that major therapy with fluoroquinolones was an independent protective factor for LOS >14 days in all patients and for hospital LOS >21 days in critically ill patients.²

Q5. What are the benefits of using fluoroquinolones for the treatment of patients with KPLA? Are there any differences between the different generation/types of fluoroquinolones?

We concluded that fluoroquinolone is an effective alternative treatment for KPLA that results in a shorter duration of IV therapy and hospital LOS. In my recent study,² among the 35 patients receiving a fluoroquinolone, 19 received levofloxacin, 10 received moxifloxacin and 6 received ciprofloxacin. Due to the limited number of cases, we did not compare the different outcomes among the three fluoroquinolones. In my opinion, the different fluoroquinolones do not impact the outcomes of KPLA.

References

1. Chuang C, et al. Gut Pathog 2016:8:46.
2. Chuang C, et al. Int J Antimicrob Agents 2020;56:106120.
3. Siu LK, et al. Lancet Infect Dis 2012;12:881-887.
4. Yu WL, Chuang YC. Invasive liver abscess syndrome caused by Klebsiella pneumoniae. Available at: https://www.uptodate.com/contents/invasive-liver-abscess-syndrome-caused-by-klebsiella-pneumoniae. Accessed 2 July 2021.
5. Lin YT, et al. J Infect Dis 2013;208:211-217.
6. Lin YT, et al. Antimicrob Agents Chemother 2020; 64:e00174-20.
7. Kim HA, et al. Diagn Microbiol Infect Dis 2015;81:60-65.
8. Lee SS, et al. Clin Infect Dis 2008;47:642-650.
9. Park SY, et al. J Infect 2017;75:590–593 .
10. Molton JS, et al. Clin Infect Dis 2020;71:952–959.