Version May 2024
INTRODUCTION — Klebsiella pneumoniae is a member of the Klebsiella genus of Enterobacteriaceae and belongs to the normal flora of the human mouth and intestine. Of the pathogenic Klebsiella species, K. pneumoniae is the most prevalent and clinically important. Infections with K. pneumoniae are usually hospital-acquired and occur primarily in patients with impaired host defenses.
An important exception to these general observations is a community-acquired invasive primary liver abscess syndrome, which can occur in patients without any underlying predisposing medical conditions and has primarily been described in countries in East Asia, particularly Taiwan [1]. (See "Invasive liver abscess syndrome caused by Klebsiella pneumoniae".)
The epidemiology, clinical features, diagnosis, and treatment of infections due to K. pneumoniae will be reviewed here. The microbiology and pathogenesis of K. pneumoniae infection are discussed separately. (See "Microbiology and pathogenesis of Klebsiella pneumoniae infection".)
EPIDEMIOLOGY — Humans are the primary reservoir for K. pneumoniae. Carrier rates of K. pneumoniae in the community range from 5 to 38 percent in stool samples and 1 to 6 percent in the nasopharynx; Klebsiella species are rarely carried on the skin [2]. Higher rates of nasopharyngeal carriage have been noted in ambulatory alcoholic patients [3]. Chinese ethnicity itself might be a major risk factor for intestinal colonization; stool carrier rates of K. pneumoniae in healthy Chinese adults ranged from 19 percent in Japan to 88 percent in Malaysia [4].
Carrier rates are markedly increased in hospitalized patients, among whom reported rates are 77 percent in the stool, 19 percent in the pharynx, and 42 percent on the hands [2]. The higher rates of colonization are primarily related to the use of antibiotics [2,5,6]. This increase in prevalence is important clinically since, in one report, Klebsiella nosocomial infection was four times higher in stool carriers compared with noncarriers [7]. Similarly, in a study of 855 patients with K. pneumoniae liver abscess in Taiwan and 3420 age- and sex-matched controls, ampicillin or amoxicillin use within the prior 30 days of diagnosis (but not the prior 31 to 90 days) was associated with an increased risk of liver abscess [8].
K. pneumoniae can also be found in soil and water, and organisms from coastal water can be a zoonotic pathogen of marine mammals [9-11]. As an example, in Taiwan, a liver abscess caused by K. pneumoniae was identified in a red-footed tortoise, and the isolate was genetically related to abscess-forming pathogens in humans [12].
There may be seasonal variation in the occurrence of K. pneumoniae infections, as illustrated by a study that found a higher incidence of K. pneumoniae bloodstream infections during the warmer months across four continents [13]. This association was not seen with Enterobacter or Serratia infections.
Host risk factors — The rate of K. pneumoniae infection is increased in individuals with impaired host defenses (eg, diabetes mellitus, alcoholism, malignancy, hepatobiliary disease, chronic obstructive pulmonary disease, glucocorticoid therapy, and renal failure) [14-24]. In a series of 101 patients with Klebsiella bacteremia, for example, underlying diabetes was present in 36 percent and malignancy in 26 percent [17]. However, the relative importance of diabetes and malignancy as risk factors varies with site of acquisition [15].
Rare cases have raised the possibility of certain occupational exposures as risk factors for infection, as illustrated by a report of food handlers who developed K. pneumoniae central nervous system infections [25].
Site of acquisition — Infections caused by K. pneumoniae can be acquired in the hospital setting, in long-term care facilities such as nursing homes (called non-nosocomial healthcare-associated infections), and, less often, in the community [2,6,15,17,20-22,26].
It has been estimated that Klebsiella species account for 3 to 8 percent of all nosocomial bacterial infections, with the most common manifestations being urinary tract infection, pneumonia, and primary bacteremia [2,27]. The major risk factors for such infections are prior antibiotic use and use of invasive plastic devices, such as bladder catheters, endotracheal tubes, and intravenous catheters [2,6,21]. Widespread antibiotic use is also responsible for the development of multidrug resistance in K. pneumoniae. (See 'Resistant organisms' below.)
The predisposing diseases and site of infection appear to vary with the site of acquisition. This was illustrated in a prospective study from Taiwan of 158 consecutively hospitalized patients with K. pneumoniae bacteremia seen between 1997 and 1999 [15]:
●Underlying diabetes was significantly more common with community-acquired infection (49 versus 13 percent), whereas malignancy was significantly more common with nosocomial infection (53 versus 14 percent). Among community-acquired infections, diabetes is a particular risk factor for primary liver abscess. (See 'Liver abscess' below and "Invasive liver abscess syndrome caused by Klebsiella pneumoniae", section on 'Pathogenesis and risk factors'.)
●All cases of liver abscess were community acquired, and liver abscess was identified in 23 percent of community-acquired infections. An inability to identify a primary source of infection was significantly more common with nosocomial bacteremia (58 versus 16 percent of community-acquired bacteremias).
Geographic distribution — Although nosocomial K. pneumoniae infections occur worldwide, some types of community-acquired infection are seen in only a few areas. As an example, regional differences in the primary source of K. pneumoniae bacteremia were evaluated in a review of 455 consecutive cases in seven countries (Taiwan, South Africa, United States, Australia, Belgium, Turkey, and Argentina) [28]. Community-acquired pneumonia was seen only in Taiwan and South Africa and the invasive community-acquired syndrome of liver abscess, meningitis, or endophthalmitis was only seen in Taiwan. However, sporadic cases of primary K. pneumoniae liver abscess are now being reported worldwide. (See "Invasive liver abscess syndrome caused by Klebsiella pneumoniae", section on 'Epidemiology'.)
Virulence factors in the K. pneumoniae isolates appeared to play a significant role in the geographic restriction of these syndromes. The isolates from Taiwan and South Africa compared with the other countries were much more likely to have a mucoid phenotype (100 versus 2 percent) and to be rmpA-positive (86 versus 7 percent). Other virulence factors, such as K1 capsular serotype, were common in Taiwan and South Africa but rarely seen in the other countries. Furthermore, in other studies from Taiwan, an increased number of virulence factors have been particularly associated with community-acquired primary liver abscess [1,29]. (See "Microbiology and pathogenesis of Klebsiella pneumoniae infection", section on 'Pathogenesis' and "Invasive liver abscess syndrome caused by Klebsiella pneumoniae", section on 'Virulence factors'.)
The increased virulence associated with community-acquired infections in these regions is not seen in most other countries. As an example, a report of 241 patients with Klebsiella bacteremia from Israel found significantly higher rates of both shock and mortality with nosocomial infections (65 and 42 versus 37 and 22 percent in community-acquired infections) [30].
CLINICAL SYNDROMES — K. pneumoniae is primarily a nosocomial pathogen that has been associated with urinary tract infection, pulmonary infection, bacteremia, and other infections in susceptible individuals who have the risk factors described above. Community-acquired infections are less common and include pneumonia, urinary tract infection, and, primarily in East Asia (particularly Taiwan), a liver abscess syndrome that may be associated with metastatic infections such as endophthalmitis and/or meningitis.
Pulmonary infection — K. pneumoniae pulmonary infections include nosocomial (hospital-acquired) pneumonia, community-acquired pneumonia, secondary infection in patients with chronic obstructive pulmonary disease (COPD), lung abscess, and empyema (image 1).
Nosocomial pneumonia — K. pneumoniae is a relatively common cause of nosocomial pneumonia. This was illustrated in a review of 4543 patients with pneumonia in United States hospitals between January 2002 and December 2003 [31]. K. pneumoniae accounted for 8.4 percent of cases of ventilator-associated pneumonia (VAP), 7.1 percent of cases of non-ventilated hospital-acquired pneumonia (defined as first positive culture more than two days after admission), and 7.6 percent of cases of healthcare-associated pneumonia (eg, infections occurring in long-term care facilities, also called non-nosocomial healthcare-associated pneumonia). In other series, K. pneumoniae accounted for 2 to 3.3 percent of cases of VAP [32,33] and 4.8 percent of cases of non-ventilated hospital-acquired pneumonia [32]. (See "Epidemiology, pathogenesis, microbiology, and diagnosis of hospital-acquired and ventilator-associated pneumonia in adults", section on 'Pneumonia types'.)
The clinical manifestations of nosocomial pneumonia due to K. pneumoniae are similar to the typical presentation of nosocomial or ventilator-associated pneumonia in general, namely new pulmonary infiltrate with fever, cough, increased sputum production, and leukocytosis. Nosocomial colonization of the upper respiratory tract is common in hospitalized patients, particularly in patients who require ventilator support or admission to an intensive care unit. Thus, isolation of Klebsiella from the sputum of a hospitalized patient without other signs and symptoms of pneumonia may not be indicative of an infection. (See "Clinical presentation and diagnostic evaluation of ventilator-associated pneumonia", section on 'Diagnostic evaluation'.)
Nosocomial K. pneumoniae pulmonary infections usually present as bronchopneumonia or bronchitis. In a series of 198 cases of acute K. pneumoniae pneumonia, the majority of which were nosocomial, the most common CT findings were ground glass opacities (100 percent), alveolar consolidation (91 percent), intralobar reticular opacities (86 percent), and pleural effusions (53 percent) [34].
On Gram stain of the sputum, short, plump, gram-negative bacilli that are usually surrounded by a capsule that appears as a clear space can be seen in nosocomial K. pneumoniae pneumonia (picture 1). However, this finding is not specific, as other organisms may also appear this way. Other pathogens, specifically Staphylococcus aureus or Pseudomonas aeruginosa, may be found in addition to K. pneumoniae in the sputum from nosocomial cases more frequently than community-acquired cases [35]. Additionally, Klebsiella isolates in nosocomial cases are more likely to be multidrug-resistant. (See 'Resistant organisms' below.)
Community-acquired pneumonia — The frequency of K. pneumoniae as a cause of community-acquired pneumonia (CAP) varies by location (with higher frequencies in Asian countries). It is an infrequent cause in the United States and Europe and most often occurs in alcoholics and patients with diabetes or severe chronic obstructive pulmonary disease [36]. In studies of patients with CAP in such places as the Netherlands and Iran, K. pneumoniae was a rare cause [37,38]. However, in a study of 225 adults in Shanghai, China who had CAP with a pathogen isolated, K. pneumoniae was one of the top three isolates (10 percent of cases) [39].
Similarly, in a global review of 202 episodes of community-acquired K. pneumoniae bacteremia, only four cases of bacteremic pneumonia were noted in the United States, Europe, Argentina, and Australia [14]. On the other hand, 53 cases were noted in South Africa and Taiwan. K. pneumoniae is also a more likely co-pathogen in the setting of severe influenza in Taiwan [40] compared with other locations, such as Mexico and Spain [41,42].
K. pneumoniae constitutes a higher proportion of isolates in more severe cases of CAP. In a study from Taiwan, K. pneumoniae was the most common bacteria isolated from 59 patients with CAP requiring mechanical ventilation [43]. Additionally, in three separate series, the proportion of K. pneumoniae isolates was 9.5 percent in patients with CAP requiring admission, 11 percent in patients presenting with septic shock, and 22 percent in patients with severe CAP (one-half with shock) [31,44,45].
The clinical manifestations of K. pneumoniae pneumonia are similar to those of other causes of bacterial pneumonia (eg, cough, fever, pleuritic chest pain, dyspnea, tachypnea, sputum production, crackles on physical examination, and leukocytosis). However, K. pneumoniae pneumonia is also associated with marked inflammation and necrosis that can lead to thick, mucoid and blood-tinged sputum, referred to as "currant jelly" sputum. (See "Clinical evaluation and diagnostic testing for community-acquired pneumonia in adults", section on 'Clinical evaluation'.)
In contrast to the radiographic findings in nosocomial cases, community-acquired K. pneumoniae often produces a lobar pneumonia that is similar radiologically to that due to Streptococcus pneumoniae [34,46]. There is a predilection for involvement of the posterior segment of the right upper lobe. Bowing of the fissure downward due to intense consolidation can led to the bulging fissure sign (image 1). The distinction of Klebsiella as a cause of community-acquired pneumonia cannot be made on radiographic findings alone.
On Gram stain of sputum, Klebsiella species typically appear as short, plump, gram-negative bacilli, which are usually surrounded by a capsule that appears as a clear space (picture 1). However, this finding is not specific, as other organisms may also appear this way.
Even with early and appropriate antimicrobial therapy, mortality rates of K. pneumonia CAP are high, particularly in the setting of associated bacteremia [47-49]. As an example, in a series of 91 patients with K. pneumoniae CAP in Taiwan, the mortality rate was 30 percent [47]. In a study of patients with CAP with bacteremia, the 49 patients with infections due to K. pneumoniae had a higher mortality rate than the 44 patients with S. pneumoniae (55 versus 27 percent) [48]. Respiratory failure is a frequent cause of death in patients with lobar pneumonia, particularly when there is rapid dissemination to multiple lobes or progression to acute respiratory distress syndrome.
COPD with secondary infection — In China and Taiwan, Klebsiella and other gram-negative bacilli are relatively frequent isolates in acute exacerbations of COPD [23,24,50]. In one study of 494 acute COPD exacerbations in patients hospitalized at a university-affiliated hospital in Taiwan, the predominant identifiable sputum pathogens were K. pneumoniae (20 percent), P. aeruginosa (17 percent) and Haemophilus influenzae (8 percent); S. pneumoniae accounted for only 2.4 percent [23]. In the US and Europe, K. pneumoniae is less frequently isolated than H. influenzae, Moraxella catarrhalis, and S. pneumoniae [51,52].
The clinical manifestations are similar to those of COPD exacerbations from other bacterial causes. (See "Management of infection in exacerbations of chronic obstructive pulmonary disease", section on 'Introduction'.)
Lung abscess — In general, K. pneumoniae is an uncommon cause of lung abscess, which is caused most frequently by anaerobes that make up the flora of the gingival crevice. (See "Lung abscess in adults".)
However, the bacteriology of lung abscess may be different in Taiwan, as illustrated by the findings of a retrospective evaluation of 90 adults hospitalized with lung abscess from 1995 to 2003 [53]. Gram-negative bacilli, and K. pneumoniae specifically, accounted for 36 and 25 percent of isolates, respectively; other organisms included anaerobes (34 percent), gram-positive cocci (26 percent), and gram-positive bacilli (4 percent). This is in contrast to a study from Japan of patients with community-acquired lung abscess from 1994 to 2008, among whom K. pneumoniae was an identified pathogen in only 8 percent of 122 patients with documented etiologic pathogens (5.3 percent of total isolates) [54].
An accompanying editorial noted that the study from Taiwan might have been biased since 25 percent of the patients had received antibiotics prior to culture, making recovery of anaerobes less likely [55]. In addition, there may have been selection bias in terms of when transthoracic aspiration was performed, since only 90 of 336 cases of lung abscess (27 percent) had evaluable microbiologic studies. Additionally, the risk of lung abscess with K. pneumoniae pulmonary disease may be relatively low, even in Taiwan; in a series of 49 cases of bacteremic K. pneumoniae community-acquired pneumonia, concurrent lung abscess was only found in 3 cases [48].
In the Taiwan series, K. pneumoniae lung abscess was significantly associated with underlying diabetes mellitus [53]. None of the patients with K. pneumoniae lung abscess were noted to have putrid sputum, one-third presented with a dry cough, and one-third had ongoing symptoms for greater than 30 days. Compared with anaerobic lung abscess, K. pneumoniae lung abscess was associated with significantly higher rates of concomitant bacteremia, delayed defervescence, and multiple cavities on chest x-ray (odds ratio 9.4, 9.2, and 11, respectively). This finding was consistent with the observation that invasive community-acquired K. pneumoniae infection in Taiwan is significantly associated with an unusually virulent strain [29]. Specifically, lung abscess caused by K. pneumoniae with K1 capsular serotype was first reported in Taiwan [56]. Scattered cases of necrotizing pneumonia caused by these virulent K. pneumoniae strains are now being seen worldwide, including the United States [57]. (See "Microbiology and pathogenesis of Klebsiella pneumoniae infection", section on 'Pathogenesis'.)
In addition to being a primary pulmonary infection, K. pneumoniae lung abscess can represent a metastatic infection in patients with the community-acquired invasive liver abscess syndrome [58-60] or with pyomyositis [61]. (See "Invasive liver abscess syndrome caused by Klebsiella pneumoniae", section on 'Metastatic infection'.)
Empyema — K. pneumoniae is a relatively common isolate in patients with empyema, as illustrated by the following observations:
●In a review of 197 patients with empyema at two military hospitals in the United States, K. pneumoniae was isolated in 16 (8 percent), 6 as a single organism [62].
●K. pneumoniae is a more common cause of empyema in Taiwan, as it is for lung and liver abscess as noted above. This was illustrated in a study of 171 patients with acute thoracic empyema [63]. A total of 163 organisms were isolated from the pleural fluid of 139 patients. K. pneumoniae was the most commonly isolated pathogen (24 percent of patients) and was strongly associated with a diagnosis of diabetes mellitus.
In a retrospective analysis of 147 cases of empyema or complicated parapneumonic effusion in Taiwan, patients with monomicrobial pleural infection with K. pneumoniae had similar symptoms as those without K. pneumoniae infection. Fever, chest pain, cough, sputum production, and dyspnea, occurred in 46, 54, 60, 51, and 73 percent respectively [64]. However, those with K. pneumoniae pleural disease had higher progression to shock within 2 days (14 versus 4 percent) and in-hospital mortality (32 versus 13 percent). (See "Epidemiology, clinical presentation, and diagnostic evaluation of parapneumonic effusion and empyema in adults", section on 'Clinical features'.)
Bacteremia — K. pneumoniae is a relatively common cause of gram-negative bacillary bacteremia, more frequently in nosocomial than community-acquired infections [65-68].
Clinical findings associated with K. pneumonia bacteremia were evaluated in a retrospective analysis of 640 cases in Canada [69]. Seventy percent of cases were nosocomial or healthcare related and 30 percent were community-acquired. The median age was 69 years old, and the most important risk factors were solid organ transplantation, chronic liver disease, dialysis dependence, and malignancy. The biliary and genitourinary tracts were the most common primary sites of infection. The overall mortality rate was 20 percent, and higher with older age, nosocomial infection, nonbiliary and nongenitourinary sources, and comorbid conditions. Admission to an intensive care unit, having a solid organ tumor, and underlying pneumonia have also been associated with high mortality [70]. These clinical findings are similar to those seen for bacteremia due to gram-negative bacilli in general. (See "Gram-negative bacillary bacteremia in adults".)
A primary source of infection is not identifiable in 30 to 47 percent of patients [15,69,71]. This is more likely to occur in nosocomial compared with community-acquired infections. Given the high prevalence of primary liver abscess in patients with community-acquired bacteremia in East Asia, imaging for liver abscess, usually with ultrasonography or computed tomography, may be warranted in patients with community-acquired K. pneumoniae bacteremia of uncertain origin, particularly those who have persistent fever despite appropriate antibiotic therapy. (See 'Liver abscess' below and "Pyogenic liver abscess".)
Catheter-related bacteremia — Nosocomial bloodstream infections (BSIs) are frequently associated with catheters, although Klebsiella is a relatively infrequent cause of catheter-related BSIs. In a prospective analysis from the SCOPE database of 24,179 nosocomial BSIs occurring in 49 hospitals in the United States between 1995 and 2002, the majority of which had central venous catheters in place, K. pneumoniae accounted for only 5 percent [72]. The gram-positive aerobes, coagulase-negative staphylococci, S. aureus, and Enterococcus, accounted for 60 percent of the BSIs. (See "Intravascular catheter-related infection: Epidemiology, pathogenesis, and microbiology", section on 'Microbiology'.)
The diagnosis and treatment of central venous catheter-related BSIs are discussed separately. (See "Intravascular non-hemodialysis catheter-related infection: Clinical manifestations and diagnosis" and "Intravascular non-hemodialysis catheter-related infection: Treatment".)
Infective endocarditis — Gram-negative bacilli, including K. pneumoniae, are uncommon causes of infective endocarditis (IE) [73-76]. As an example, gram-negative bacilli accounted for only 2.1 percent of cases in a study of 1779 patients seen between 2000 and 2003 in 39 medical centers in 16 western countries [73]. Similarly, in a series of 315 definite or possible cases of IE from Taiwan, only one was due to K. pneumoniae [75]. Even patients with K. pneumoniae bacteremia are at low risk for IE (1 of 86 in one report) [74].
The low rate of K. pneumoniae as a cause of IE may be related in part to decreased adherence of these organisms to heart valves compared with the gram-positive organisms that account for most cases of IE (viridans streptococci, coagulase-positive and coagulase-negative staphylococci, and enterococci) and to P. aeruginosa [76]. (See "Native valve endocarditis: Epidemiology, risk factors, and microbiology", section on 'Microbiology'.)
Thus, among patients with K. pneumoniae bacteremia, evaluation for IE with transthoracic and/or transesophageal echocardiography should be performed only when the diagnosis is suspected clinically or the patient is at high risk (eg, significant or new heart murmur, prosthetic heart valve). (See "Clinical manifestations and evaluation of adults with suspected left-sided native valve endocarditis".)
Genitourinary tract infection — K. pneumoniae can cause both lower and upper urinary tract infection, although it is a much less common urinary pathogen than E. coli [77-79].
Cystitis and pyelonephritis — In two large series of over 2400 women with acute cystitis [78] and over 2400 outpatients with acute pyelonephritis [77], K. pneumoniae was isolated in 3 to 4 percent of cases whereas E. coli accounted for approximately 80 percent. The clinical findings of urinary tract infections caused by K. pneumoniae are similar to those caused by other bacterial pathogens. (See "Acute simple cystitis in adult and adolescent females".)
K. pneumoniae can also cause emphysematous (gas-forming) urinary tract infections, which primarily occur in patients with diabetes mellitus and may be associated with urinary tract obstruction [80-82]. (See "Emphysematous urinary tract infections".)
Renal and perinephric abscess — Renal abscess can develop by one of two general mechanisms: hematogenous spread, which usually results in a cortical abscess; and, less often, ascending infection from the bladder, which primarily involves the medulla. The features of K. pneumoniae renal abscess were illustrated in a retrospective review of 24 patients in Taiwan [82]. The major predisposing factors were diabetes mellitus (58 percent), urolithiasis (25 percent) and immunosuppression (17 percent). Complications included bacteremia (54 percent), emphysematous pyelonephritis (21 percent), and metastatic infection (13 percent). Metastatic infection manifested as endophthalmitis has been noted in other reports [83,84]. (See 'Endophthalmitis' below.)
Perinephric abscess can result from hematogenous spread or develop as a complication of pyelonephritis. Both abscess types usually present with manifestations similar to acute pyelonephritis, such as fever, chills, and flank pain. (See "Renal and perinephric abscess".)
Prostatitis and prostatic abscess — K. pneumoniae is generally an infrequent cause of both prostatitis and prostatic abscess [85,86]. In a review of 1442 patients with chronic prostatitis in Croatia, for example, an infectious cause was found in 1070; K. pneumoniae was responsible for only 16 (1.5 percent) [85]. An exception to this observation was noted in a study from Taiwan in which 10 of 17 cases of prostatic abscess, a severe complication of prostatitis, were due to K. pneumoniae [87].
The most severe forms of prostatic infection caused by K. pneumoniae are emphysematous (gas-forming) prostatitis and emphysematous prostatic abscess. Risk factors include diabetes mellitus and chronic alcoholism, and most reports of these rare complications come from East Asia [88-90].
In addition to being a local infection, K. pneumoniae prostatic abscess can represent a metastatic infection in patients with the community-acquired invasive liver abscess syndrome [59]. On the other hand, prostatitis or prostatic abscess can lead to metastatic infections, including endophthalmitis, septic arthritis, and osteomyelitis [91-93]. (See "Invasive liver abscess syndrome caused by Klebsiella pneumoniae", section on 'Metastatic infection' and 'Endophthalmitis' below.)
Patients with acute prostatic infections often present with fever and chills, dysuria, obstructive urinary symptoms, and pelvic or perineal pain. On exam, the prostate is usually tender, warm, and edematous. In emphysematous prostatitis, imaging studies demonstrate the presence of gas in the prostate [89]. The clinical manifestations of prostatic infections are discussed in detail elsewhere. (See "Acute bacterial prostatitis", section on 'Clinical manifestations'.)
Intraabdominal infections
Liver abscess — K. pneumoniae is a frequent isolate from pyogenic liver abscesses, which are typically polymicrobial and associated with underlying hepatobiliary pathology or cholangitis (image 2). In case series from New York and San Diego, K. pneumoniae was the most common cause of pyogenic hepatic abscess [94,95].
In the report from New York, the clinical features of 171 cases of pyogenic liver abscesses were reviewed [94]. The most common presenting symptoms were fever (90 percent), right upper quadrant pain (72 percent) and chills (69 percent). The triad of fever, right upper quadrant pain or tenderness, and elevated alkaline phosphatase were seen in only 43 percent, but 86 percent had at least two of those features. K. pneumoniae was isolated from 23 of 54 (41 percent) liver abscesses in which an organism was recovered, and clinical characteristics were similar to the patients with liver abscesses of other or unknown etiologies. (See "Pyogenic liver abscess", section on 'Clinical manifestations'.)
A distinct clinical syndrome, primary liver abscess (ie, in the absence of underlying hepatobiliary disease) due to K. pneumoniae, has been recognized as an important community-acquired infection in East Asia, particularly Taiwan [1,58,96]. This entity is seen less often in other countries but may account for the frequency of K. pneumonia isolates from liver abscesses outside of Asia [94,95,97]. In the series from New York described above, of the 23 cases of K. pneumonia liver abscess, only one occurred in a patient with underlying hepatobiliary disease, and all affected patients were Asian or Hispanic [94]. The syndrome of Klebsiella primary liver abscess is discussed in detail separately. (See "Invasive liver abscess syndrome caused by Klebsiella pneumoniae".)
Splenic abscess — K. pneumoniae has been reported in 10 to 16 percent of cases of splenic abscess from two series [98,99]. In studies from Taiwan, many of these patients also had concurrent liver abscess [99-101]. This raises the possibility of splenic abscess representing a metastatic infection in patients with primary liver abscess, an association that has been described by others [58]. (See 'Liver abscess' above and "Invasive liver abscess syndrome caused by Klebsiella pneumoniae", section on 'Metastatic infection'.)
The most common presenting features of splenic abscesses are fever, left upper quadrant pain, splenomegaly, and left pleural effusion. (See "Splenomegaly and other splenic disorders in adults", section on 'Abscess and infarction'.)
Spontaneous bacterial peritonitis — Spontaneous bacterial peritonitis (SBP) is defined as an ascitic fluid infection without an evident intraabdominal surgically-treatable source [102]. It almost always occurs in patients with cirrhosis and ascites. Patients typically present with fever and abdominal pain and have an elevated polymorphonuclear leukocyte count in the ascitic fluid. (See "Spontaneous bacterial peritonitis in adults: Clinical manifestations".)
Among patients with SBP and positive ascitic fluid cultures, more than 60 percent are due to gram-negative enteric flora [102]. E. coli is most common, followed by K. pneumoniae, which is present in approximately 10 to 15 percent of cases (table 1) [103,104]. This applies to both community-acquired and nosocomial infections [104].
Endophthalmitis — Endogenous endophthalmitis caused by K. pneumoniae is an infrequent but often devastating septic metastatic infection. It has mostly been described in association with primary liver abscess in patients from East Asia, particularly Taiwan [1,58,59,96,105-107], but also in patients in the United States [95]. In three series from Taiwan with a total of 524 patients with K. pneumoniae liver abscess, metastatic infection occurred in 12 percent, one-half of whom (6 percent total) had endophthalmitis [1,58,59]. (See "Invasive liver abscess syndrome caused by Klebsiella pneumoniae", section on 'Metastatic infection'.)
Metastatic K. pneumoniae endophthalmitis is not limited to primary liver abscess and has been rarely reported with other K. pneumoniae infections including perinephric abscess [83,84], pyelonephritis [108], prostatitis [91], prostatic abscess [92], and pulmonary infection [109].
Patients with Klebsiella endophthalmitis commonly complain of ocular pain, visual blurring, and eye redness [110]. Unilateral disease is often more common than bilateral. The infection tends to be fulminant and often rapidly progresses to permanent visual loss, particularly with a delay in diagnosis and treatment beyond 24 hours after symptom onset [1,105-107,111]. In a retrospective review of 61 patients with endogenous K. pneumoniae endophthalmitis, 87 percent had poor visual acuity (less than 4/200) at presentation [110]. At three months postinfection, 76 percent still had poor visual acuity and 58 percent had no light perception. Hypopyon (layering of white blood cells in the anterior chamber) was common (72 percent) and a poor prognostic indicator. Good vision at presentation and early initiation of therapy have been associated with a higher likelihood of maintenance of vision [105,106].
Endophthalmitis should be considered in any patient complaining of unilateral or bilateral decreased or blurred vision or eye pain in the setting of K. pneumoniae infections. (See "Bacterial endophthalmitis", section on 'Endogenous bacterial endophthalmitis'.)
Conversely, the possibility of a separate focus of K. pneumoniae infection, particularly a liver abscess, should be suspected and evaluated in patients who have endogenous endophthalmitis due to K. pneumoniae. (See "Invasive liver abscess syndrome caused by Klebsiella pneumoniae", section on 'Diagnosis'.)
Meningitis/brain abscess — K. pneumoniae is a relatively common cause of nosocomial meningitis (image 3). In a series of 151 cases from the United States, for example, K. pneumoniae accounted for 13 of them (8.6 percent) [112]. Neurosurgery is the main risk factor for nosocomial meningitis [113,114], and the likelihood of postneurosurgery meningitis due to gram-negative organisms such as K. pneumoniae was increased when prophylaxis for gram-positive pathogens was administered [113]. (See "Health care-associated meningitis and ventriculitis in adults: Clinical features and diagnosis" and "Antimicrobial prophylaxis for prevention of surgical site infection in adults", section on 'Neurosurgery'.)
In contrast to nosocomial meningitis, K. pneumoniae is a rare cause of community-acquired bacterial meningitis in the United States and Europe as illustrated by the following observations:
●In a report of 253 cases from the United States, all gram-negative bacilli accounted for 9 of 253 cases (3.6 percent); data were not given for specific organisms [112].
●In a review of 696 cases from the Netherlands, only one was due to K. pneumoniae [115].
In a small series of community-acquired K. pneumoniae meningitis, chronic alcoholism was a major risk factor [116,117].
An exception to the rarity of K. pneumoniae as a cause of community-acquired bacterial meningitis or brain abscess is the development of meningitis and/or brain abscess as a metastatic complication of primary K. pneumoniae liver abscess that is community-acquired and mostly seen in East Asia, particularly Taiwan [1,58,59,118]. In three series from Taiwan with a total of 524 patients with K. pneumoniae liver abscess, metastatic infection occurred in 12 percent, one-third of whom (4.2 percent) had meningitis and/or brain abscess [1,58,59]. Meningitis is more common than brain abscess and some patients have both [1,59]. (See "Invasive liver abscess syndrome caused by Klebsiella pneumoniae", section on 'Metastatic infection'.)
In a series of nine patients with metastatic central nervous system K. pneumoniae infection, five had significant persistent neurologic deficits after therapy [1]. One predictor of an adverse outcome is the neurologic status at the time of initiation of therapy with an appropriate antibiotic. In a series of 29 patients with K. pneumoniae meningitis treated with an appropriate antibiotic, the main predictor of an adverse outcome was a Glasgow coma scale of 7 points or less (table 2) [119]. (See "Stupor and coma in adults", section on 'Glasgow Coma Scale'.)
Fever and signs of central nervous system infection such as altered mental status, seizures, or nuchal rigidity are present in most patients with meningitis due to a gram-negative organism, including K. pneumoniae. In a series from Taiwan, patients with community-acquired and nosocomial K. pneumonia meningitis had similar presenting features, with the exception of less frequent nuchal rigidity in patients with nosocomial meningitis (50 versus 94 percent in community-acquired cases) [119]. The CSF findings of high leukocytes, high protein, and low glucose were reported with similar high frequency in both groups. Gram stain demonstrated visible gram-negative rods in less than one-third of cases. The clinical features of gram-negative bacillary meningitis are discussed in further detail elsewhere. (See "Health care-associated meningitis and ventriculitis in adults: Clinical features and diagnosis".)
Deep neck abscess — In Taiwan, K. pneumoniae is an important etiology of deep neck space infections, which elsewhere are caused mainly by anaerobes and streptococci. In a Taiwanese review of 100 community-acquired fascial space infections of the head and neck, K. pneumoniae was the most common pathogen in the 65 monomicrobial infections (48 percent) [120]. Similar findings were noted in another report, with K. pneumoniae being the most common pathogen with parotid infections [121]. In both series, K. pneumoniae infection was more prevalent in patients with diabetes.
The clinical manifestations of deep neck abscess depend on the primary source of infection and the extent of tissue involvement. The clinical features of deep neck space infections are discussed in detail elsewhere. (See "Deep neck space infections in adults", section on 'General clinical features'.)
In addition to being a primary infection, K. pneumoniae neck abscess can represent a metastatic infection in patients with the community-acquired invasive liver abscess syndrome [60]. In addition, deep neck abscess may be the source of metastatic infection to other sites [122]. (See "Invasive liver abscess syndrome caused by Klebsiella pneumoniae", section on 'Metastatic infection'.)
Skin and soft tissue infection — K. pneumoniae can cause severe cellulitis with or without crepitation that may progress to potentially fatal necrotizing fasciitis [123-126] or necrotizing myositis [127,128]. K. pneumoniae is an infrequent cause of these infections in western countries but is a more common cause in Taiwan [123,124,126] and, in one series, was the most commonly isolated pathogen [123]. Patients with necrotizing soft tissue infections can present with pain, swelling, and erythema of the affected site and with systemic toxicity, although in some patients, excruciating pain in the absence of any cutaneous findings is the only initial sign or symptom. In a small series of 15 cases of monomicrobial K. pneumoniae necrotizing fasciitis from Taiwan, concomitant bacteremia (80 percent) and distant abscesses (27 percent) were common [126]. (See "Necrotizing soft tissue infections".)
In addition to occurring as a primary infection, K. pneumoniae necrotizing fasciitis can represent a metastatic infection in patients with the invasive liver abscess syndrome [1,129]. (See "Invasive liver abscess syndrome caused by Klebsiella pneumoniae", section on 'Metastatic infection'.)
Other infections — K. pneumoniae has infrequently been associated with several other infections:
●Psoas muscle abscess – K. pneumoniae psoas abscess is a rare infection that has been described in case reports and small institutional series, mostly from Taiwan [122,130,131]. Fever and pain in the flank, back, and hip are the usual manifestations, and diabetes mellitus is the most common underlying disease [130]. Many of these infections reflect seeding from a distal site, such as liver abscess [58,59], urinary tract [130], or deep neck abscess [122]. Another source of infection is ruptured iliac artery mycotic aneurysm [131]. (See "Psoas abscess".)
●Spinal infection – Sporadic cases of K. pneumoniae spondylodiscitis, vertebral osteomyelitis, and spinal epidural abscess have been reported, and are usually due to primary infection or contiguous involvement from surrounding infection [132-135]. In addition, spinal infection may represent a metastatic site in patients with K. pneumoniae primary liver abscess [1,136]. (See "Vertebral osteomyelitis and discitis in adults".)
●Septic arthritis – K. pneumoniae in a rare cause of septic (bacterial) arthritis that has involved the knee or hip in isolated case reports [137-140]. The infection may be accompanied by gas formation in the joint space and in the surrounding soft tissue [137]. Septic arthritis most often arises from hematogenous spread to the joint. K. pneumoniae septic arthritis may represent a metastatic infection from liver abscess [59], prostatitis [93], or pyomyositis [61]. (See "Septic arthritis in adults".)
●Purulent pericarditis – A virulent strain with hypermucoviscosity phenotype was described in a case of purulent pericarditis [141]. Cardiac tamponade can also be a complication of pyogenic liver abscess [142]. (See "Purulent pericarditis".)
●Pyomyositis – The presumed mechanism of muscle infection with K. pneumoniae is transient bacteremia, leading to seeding of a site of prior muscle injury [61,143]. Other foci of metastatic infection may be present, including liver abscess, septic arthritis, endophthalmitis, lung abscess, and subcutaneous abscesses [61]. (See "Primary pyomyositis".)
●Mycotic aneurysm – In general, K. pneumoniae is an infrequent cause of mycotic aneurysm, which is more commonly caused by S. aureus and Salmonella spp. However, in Taiwan, K. pneumoniae is one of the pathogens more frequently associated with mycotic aneurysm [144]. Two cases of mycotic aneurysm caused by hypermucoviscous K. pneumoniae strains have been separately described in Taiwan [145,146]. (See "Overview of infected (mycotic) arterial aneurysm".)
DIAGNOSIS — The diagnosis of K. pneumoniae infection is confirmed by culture of blood, sputum, urine, or aspirated body fluid, including pleural effusion, pericardial effusion, synovial fluid, cerebrospinal fluid, and abscess material.
In the setting of bacterial pneumonia, sputum Gram stain may provide a presumptive identification for an etiologic agent, but the sensitivity is only about 50 percent. Klebsiella spp typically appear as short, plump, gram-negative bacilli, which are usually surrounded by a capsule that appears as a clear space (picture 1).
Imaging often plays an important role in the diagnosis of infection (not specifically K. pneumoniae infection) at a variety of sites. This includes chest radiograph for suspected pneumonia and imaging for suspected abscess formation in the liver, spleen, kidney, or prostate, mycotic aneurysm, epidural abscess, and vertebral osteomyelitis. The choice of imaging tests is discussed elsewhere in the topic reviews on each of these infections.
TREATMENT
General concepts — Once the diagnosis of K. pneumoniae infection is established, the antibiotic regimen is usually determined by the results of susceptibility testing. Drainage may be warranted in patients with tissue abscesses. Patients with Klebsiella endophthalmitis should receive intravitreal antibiotics and vitrectomy in addition to systemic antibiotics. Additional factors impacting treatment are multidrug resistance or suspicion for a hypervirulent strain (ie, one associated with destructive tissue abscesses and metastatic disease). (See 'Resistant organisms' below and 'Hypervirulent strains' below.)
Treatment of the various clinical syndromes is discussed in detail in separate topic reviews.
●(See "Treatment of community-acquired pneumonia in adults who require hospitalization".)
●(See "Lung abscess in adults", section on 'Treatment'.)
●(See "Intravascular non-hemodialysis catheter-related infection: Treatment".)
●(See "Renal and perinephric abscess", section on 'Management'.)
●(See "Pyogenic liver abscess", section on 'Treatment'.)
●(See "Bacterial endophthalmitis", section on 'Endogenous bacterial endophthalmitis'.)
Resistant organisms — Increasing resistance to a broad array of antibiotics is an alarming trend with clinical strains of K. pneumoniae. The possibility of production of ESBL or carbapenemases should be taken into account when choosing an antibiotic regimen for K. pneumoniae infections.
Extended-spectrum beta-lactamases — ESBL confer resistance to most beta-lactam antibiotics, including penicillins, cephalosporins, and the monobactam aztreonam. (See "Extended-spectrum beta-lactamases" and "Beta-lactam antibiotics: Mechanisms of action and resistance and adverse effects".)
Dissemination or outbreaks of ESBL-producing K. pneumoniae strains have been reported worldwide [16,147-151]. In a prospective study of 455 consecutive episodes of nosocomial K. pneumoniae bacteremia from 12 hospitals around the world in 1996 and 1997, ESBL-producing organisms accounted for 31 percent of all episodes and 44 percent of episodes acquired in an intensive care unit [147]. Most hospitals with more than one ESBL-producing isolate had multiple strains with the same genotypic pattern, indicating patient-to-patient spread. ESBL production is associated with higher mortality in K. pneumoniae infections [71].
Prior broad-spectrum antibiotic therapy is the major risk factor for the development of multidrug (not limited to ESBL) resistance [16,147,151,152]. In the above prospective study of nosocomial K. pneumoniae bacteremia, for example, prior administration of beta-lactam antibiotics with an oxyimino group (cefuroxime, cefotaxime, ceftriaxone, ceftazidime, or aztreonam) was the major independent risk factor for ESBL infection (risk ratio 3.9) [147].
Treatment of such K. pneumoniae isolates is not different from that of other ESBL-producing species. An important clinical observation is that use of an oxyimino-beta-lactam (eg, cefotaxime, ceftriaxone, ceftazidime, or cefepime) to treat severe infections caused by ESBL-producing K. pneumoniae was associated with a high rate of treatment failure when higher breakpoints for susceptibility (eg, MIC ≤8 mcg/mL) were used to determine susceptibility. In the United States and Europe, therefore, laboratory guidelines have lowered MIC breakpoints for susceptibility of gram-negative rods, such that some isolates that were once reported as susceptible are now reported as nonsusceptible.
Treatment recommendations and other issues related to ESBL-producing organisms are discussed in detail elsewhere. (See "Extended-spectrum beta-lactamases", section on 'Treatment options'.)
Carbapenem resistance — Carbapenem-hydrolyzing beta-lactamases have also emerged in K. pneumoniae worldwide. K. pneumoniae is the most common species to harbor the K. pneumoniae carbapenemase (KPC) and New Delhi metallo-beta-lactamase (NDM-1), both of which cleave all beta-lactams and substantially reduce clinical efficacy of carbapenems and beta-lactamase inhibitors. Management of these resistant infections is discussed in detail elsewhere. (See "Carbapenem-resistant E. coli, K. pneumoniae, and other Enterobacterales (CRE)", section on 'Approach to treatment'.)
Use of broad spectrum cephalosporins and/or carbapenems is an important risk factor for the development of colonization or infection with such pathogens, although prior receipt of carbapenems is not essential for acquisition of these strains [153-155].
In addition to decreased susceptibility to beta-lactams and carbapenems, resistance genes for other antibiotics, including aminoglycosides and fluoroquinolones, are frequently present in carbapenemase-producing strains [156,157]. For KPC-carrying K. pneumoniae, resistance rates of 98 percent have been reported for the fluoroquinolones, and approximately 50 percent are resistant to gentamicin and amikacin [158]. Thus, treatment options for carbapenemase-producing K. pneumoniae are limited. (See "Carbapenem-resistant E. coli, K. pneumoniae, and other Enterobacterales (CRE)", section on 'Approach to treatment'.)
Carbapenem resistance in K. pneumoniae can also be conferred by outer membrane porin loss coexisting with ESBL and/or AmpC beta-lactamases. Specifically, loss of the expression of the porins OmpK35 and OmpK36 allows carbapenem resistance in K. pneumoniae [159,160]. Carbapenem use may select the carbapenem-resistant strains by porin loss [161]. Similar to the treatment of carbapenemase-producing K. pneumoniae, effective treatment of infections caused by K. pneumoniae resistant to carbapenems through this mechanism may need agents beyond the beta-lactam and carbapenem classes.
Infections with carbapenem-resistant K. pneumoniae are associated with mortality rates as high as 50 percent [162,163].
Hypervirulent strains — Virulent strains are prone to cause a destructive tissue abscess syndrome (eg, primary liver abscess) with possible metastatic infection [1,58,59,96]. These strains are generally susceptible in vitro to all generations of cephalosporins, although resistant strains, including those that produce an ESBL or a carbapenemase, have been described [164,165]. (See "Invasive liver abscess syndrome caused by Klebsiella pneumoniae", section on 'Virulence factors' and "Invasive liver abscess syndrome caused by Klebsiella pneumoniae", section on 'Antibiotic choice'.)
SUMMARY AND RECOMMENDATIONS
●Epidemiology and risk factors – Klebsiella pneumoniae, a gram-negative bacillus, most frequently causes infection in hospitalized patients and in those with impaired host defenses, including patients with diabetes mellitus, alcoholism, malignancy, hepatobiliary disease, chronic obstructive pulmonary disease, renal failure, and glucocorticoid therapy. The frequency, distribution, and expression of virulence factors may differ between community-acquired and nosocomial strains. (See 'Epidemiology' above.)
●Clinical syndromes
•Pulmonary infection – K. pneumoniae is a common cause of nosocomial pulmonary infections in both ventilated and unventilated patients. It is an uncommon cause of community-acquired pneumonia, but in such cases, infection is typically severe and often requires hospitalization. K. pneumoniae can also cause empyema. (See 'Pulmonary infection' above.)
•Bacteremia – K. pneumoniae is a relatively common cause of nosocomial bacteremia. However, infective endocarditis due to K. pneumoniae is rare. (See 'Bacteremia' above and 'Infective endocarditis' above.)
•Other syndromes – Other clinical K. pneumoniae infections include pyogenic liver abscess (either primary or in the setting of hepatobiliary disease), lower and upper genitourinary tract infections, and soft-tissue infections. (See 'Clinical syndromes' above.)
●Diagnosis – Diagnosis of K. pneumoniae is generally made by isolation of the organism from culture of the relevant specimen. On Gram stain, Klebsiella species typically appear as short, plump, gram-negative bacilli, which are usually surrounded by a capsule that appears as a clear space (picture 1). (See 'Diagnosis' above.)
●Treatment – The antibiotic regimen for infections with K. pneumoniae is usually determined by the results of susceptibility testing. Outbreaks of strains that produce an extended-spectrum beta-lactamase or a carbapenemase have been reported worldwide. (See 'Treatment' above and 'Resistant organisms' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Yin-Ching Chuang, MD, who contributed to earlier versions of this topic review.
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
