Medical Care
Initial antibiotic selection
Klebsiella organisms are resistant to multiple antibiotics. This is thought to be a plasmid-mediated property. Length of hospital stay and performance of invasive procedures are risk factors for acquisition of these strains.
Treatment depends on the organ system involved. In general, initial therapy of patients with possible bacteremia is empirical. The choice of a specific antimicrobial agent depends on local susceptibility patterns. Once bacteremia is confirmed, treatment may be modified.
Agents with high intrinsic activity against K pneumoniae should be selected for severely ill patients. Examples of such agents include third-generation cephalosporins (eg, cefotaxime, ceftriaxone), carbapenems (eg, imipenem/cilastatin), aminoglycosides (eg, gentamicin, amikacin), and quinolones. These agents may be used as monotherapy or combination therapy. Some experts recommend using a combination of an aminoglycoside and a third-generation cephalosporin as treatment for non–ESBL-producing isolates. Others disagree and recommend monotherapy.
Ceftazidime/avibactam is indicated to treat adults with complicated intra-abdominal infections (in combination with metronidazole) and complicated UTIs, including kidney infections (pyelonephritis), who have limited or no alternative treatment options. Ceftolozane/tazobactam and ceftazidime/avibactam are two novel beta-lactam/beta-lactamase combination antibiotics available. Ceftazidime/avibactam is also active against carbapenem-resistant Enterobacteriaceae that produce K pneumoniae carbapenemases. [15]
The novel carbapenem/beta-lactamase inhibitor meropenem/vaborbactam (Vabomere) specifically addresses carbapenem-resistant Enterobacteriaceae (CRE) (eg, E coli, K pneumoniae) by inhibiting the production of enzymes that block carbapenem antibiotics, one of the more powerful classes of drugs in the antibiotic arsenal. In August 2017, meropenem/vaborbactam was FDA approved for complicated urinary tract infections (cUTI) caused by CRE.
The approval was based on data from a phase 3 multicenter, randomized, double-blind, double-dummy study, TANGO-I (n=550) in adults with cUTI, including those with pyelonephritis. The primary endpoint was overall cure or improvement and microbiologic outcome of eradication (defined as baseline bacterial pathogen reduced to < 104 CFU/mL). Data showed about 98.4% of patients treated with intravenous meropenem/vaborbactam exhibited cure/improvement in symptoms and a negative urine culture result, compared with 94.3% of patients treated with piperacillin/tazobactam. About one week posttreatment, approximately 77% of patients treated with meropenem/vaborbactam had symptom resolution and a negative urine culture result, compared with 73% of patients treated with piperacillin/tazobactam. [16]
Aztreonam may be used in patients who are allergic to beta-lactam antibiotics. Quinolones are also effective treatment options for susceptible isolates in patients with either carbapenem allergy or major beta-lactam allergy.
Other antibiotics used to treat susceptible isolates include ampicillin/sulbactam, piperacillin/tazobactam, ticarcillin/clavulanate, ceftazidime, cefepime, levofloxacin, norfloxacin, moxifloxacin, meropenem, and ertapenem.
Treatment of Klebsiella pneumonia has discrepant results. For patients with severe infections, a clinically prudent approach is the use of an initial short course (48-72 h) of combination therapy with an aminoglycoside, followed by a switch to an extended-spectrum cephalosporin when susceptibility is confirmed.
Antibiotic considerations for resistant infections
Guidance by IDSA has been provided and reviewed for clinicians as this field is highly dynamic. [17]
Beta-lactamases are constitutive, are usually produced at low levels, and provide resistance against ampicillin, amoxicillin, and ticarcillin.
ESBLs are plasmid mediated, confer multidrug resistance (TEM or SHV types), and are detected by in vitro resistance to ceftazidime and aztreonam. CTX-M type ESBLs, which hydrolyze ceftazidime much less than other third- and fourth-generation cephalosporins, are more prevalent and have proliferated in the Escherichia coli ST131 lineage. [18]
K pneumoniae carbapenemases (KPC; Ambler class A beta lactamases) confer broad resistance and are associated with a higher mortality rate (>50%). Many isolates are a single sequence type, ST258. Susceptibility is limited to gentamicin, tigecycline, and colistin.
Metallo-beta-lactamases (Amber class B) include imipenemase (IMP), Verona integron-encoded MBL (VIM), and NDM-1 and are generally resistant to all antibiotics except tigecycline and colistin.
OXA-type carbapenemases (Amber class D) include OXA-48 and weakly hydrolyze carbapenems, broad-spectrum cephalosporins, and aztreonam but express resistance or decreased susceptibility to carbapenems.
ESBL-producing isolates are treated with carbapenems.
Isolates that produce carbapenemase are resistant to carbapenems, penicillins, cephalosporins, fluoroquinolones, and aminoglycosides. Treatment options are limited to colistin (preferred for UTIs), tigecycline, and, occasionally, intravenous fosfomycin.
Combination treatment with colistin, tigecycline, and carbapenem may improve survival in bacteremic patients. [2]
Consider tissue drug penetration such as lung penetration for pneumonia and urine concentration for UTIs.
For liver abscess, percutaneous drainage may be considered.
Community-acquired pneumonia
The mortality rate may be 50%, regardless of treatment.
Effective treatment for this rare condition consists of empirical coverage for gram-negative organisms, aggressive ventilation, and supportive care.
Other measures include clinical and radiologic surveillance for surgically treatable entities such as pulmonary gangrene, lung abscess, and empyema.
Third-generation cephalosporins or quinolones provide coverage for community-acquired K pneumoniae infection. In one study, combination therapy with aminoglycosides was shown to be superior; this benefit was not observed in other studies. Macrolides have no useful activity against K pneumoniae.
Antibiotic therapy should be implemented for at least 14 days.
Nosocomial K pneumoniae pneumonia
Choose antibiotics with high intrinsic activity. A regimen that includes imipenem, third-generation cephalosporins, quinolones, or aminoglycosides may be used alone or in combination. Always confirm susceptibility. Treatment should last at least 14 days.
If response is slow, chest tomography scans may be useful in helping exclude entities that are treatable with debridement or drainage.
In patients who rapidly respond to intravenous therapy, switching to an oral quinolone is regarded as safe so long as the isolate is susceptible.
K pneumoniae UTI
Uncomplicated cases caused by susceptible strains may be treated with most oral agents except ampicillin. Monotherapy is effective, and therapy for 3 days is sufficient.
Complicated cases may be treated with oral quinolones or with intravenous aminoglycosides, imipenem, aztreonam, third-generation cephalosporins, or piperacillin/tazobactam. Duration of treatment is usually 14-21 days. Intravenous agents are used until the fever resolves.
Other measures may include correction of an anatomical abnormality or removal of a urinary catheter.
Other K pneumoniae infections
Combination therapy with a beta-lactam antibiotic and an aminoglycoside is considered the standard for empiric treatment of cholangitis. Few comparative data exist to establish this as the optimal therapy.
Ciprofloxacin monotherapy is as effective as combination therapy for acute suppurative cholangitis. Antimicrobials are administered for at least 10 days. Biliary decompression may be required.
Klebsiella meningitis in adults is rare. Nosocomial disease complicates shunts in children. Third-generation cephalosporins are the drugs of choice because of superior central nervous system penetration. Reports indicate success with cefotaxime, and meropenem is a useful alternative. Adjunctive measures include removal of infected shunts. The suggested duration of treatment is 3 weeks because higher relapse rates have been noted in patients treated with shorter courses of therapy.
Klebsiella endophthalmitis and endocarditis are rare. Therapy for endophthalmitis may be intravitreal, intravenous, or both. Clinical experience is greatest with intravenous ceftazidime and aminoglycosides; however, intravenous therapy alone results in very poor drug levels at the site of infection. Endocarditis has been treated with a combination of an intravenous aminoglycoside and a beta-lactam antibiotic. Few data exist to guide treatment duration; however, 6 weeks of antibiotic therapy is considered reasonable.
Infection with other Klebsiella species
Antibiotic susceptibility and treatment guidelines for K oxytoca infection are virtually identical to those for K pneumoniae. In one study of very ill patients, K oxytoca bacteremia had a 21% mortality rate at 14 days.
Rhinoscleroma is treated with combination antimicrobial therapy for 6-8 weeks. Therapeutic choices include aminoglycosides, tetracycline, sulfonamides, rifampin, and quinolones.
Ozena may be treated with a 3-month course of ciprofloxacin. Intravenous aminoglycosides and trimethoprim/sulfamethoxazole are also useful in the treatment of these conditions. Susceptibility testing is usually required.
K granulomatis genital and mucocutaneous infections are preferably treated with doxycycline for 3 weeks and until the lesions are healed. Consider adding gentamicin if no improvement is noted within the first 36-72 hours. Alternative antibiotics include azithromycin, ciprofloxacin, erythromycin, and trimethoprim/sulfamethoxazole.
Surgical Care
Surgery is required if drainage or debridement is necessary (eg, empyema, lung abscess, pulmonary gangrene, respiratory tract obstruction following persistent K rhinoscleromatis infection).
Surgery may also be needed to correct underlying anatomic abnormalities that predispose patients to infection. An example is correction of posterior urethral valves in patients with recurrent UTIs. Cosmesis is another reason patients require surgical care. This is observed in deforming K rhinoscleroma infection.
Thoracotomy with tube placement is required for empyema.
Pleural decortication is a therapeutic option for persistent pleural adhesions, and extensive lung necrosis may require surgical resection.
Consultations
Surgical consultation is required for the conditions discussed in Surgical Care.
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This scanning electron micrograph (SEM) reveals some of the ultrastructural morphologic features of Klebsiella pneumoniae. Courtesy of CDC/Janice Carr.
