Microbial Taxonomy

E.coli,Klebsiella,proteus

Background,species,Culture, Clinical presentation,

Diagnosis, Treatment

Afaq Ahmad
5/20/2019
E.Coli
Escherichia coli is one of the most frequent causes of many common bacterial infections,
including cholecystitis, bacteremia, cholangitis, urinary tract infection (UTI), and traveler's
diarrhea, and other clinical infections such as neonatal meningitis and pneumonia.
The genus Escherichia is named after Theodor Escherich, who isolated the type species of the
genus. Escherichia organisms are gram-negative bacilli that exist singly or in pairs. E coli is
facultatively anaerobic with a type of metabolism that is both fermentative and respiratory. They
are either nonmotile or motile by peritrichous flagella. E coli is a major facultative inhabitant of
the large intestine.

Pathophysiology

Acute bacterial meningitis

The vast majority of neonatal meningitis cases are caused by E coli and group B streptococcal
infections(28.5% and 34.1% overall, respectively). Pregnant women are at a higher risk of
colonization with the K1 capsular antigen strain of E coli. This strain is also commonly observed
in neonatal sepsis, which carries a mortality rate of 8%; most survivors have subsequent
neurologic or developmental abnormalities. Low birth weight and a positive cerebrospinal fluid
(CSF) culture result portend a poor outcome. In adults, E colimeningitis is rare but may occur
following neurosurgical trauma or procedures or complicating Strongyloides
stercoralis hyperinfection involving the CNS.

Pneumonia
E coli respiratory tract infections are uncommon and are almost always associated with E
coli UTI. No virulence factors have been implicated. E coli pneumonia may also result from
microaspiration of upper airway secretions that have been previously colonized with this
organism in severely ill patients; hence, it is a cause of nosocomial pneumonia. However, E
coli pneumonia may also be community-acquired in patients who have underlying disease such
as diabetes mellitus, alcoholism, chronic obstructive pulmonary disease, and E coli UTI. E
colipneumonia usually manifests as a bronchopneumonia of the lower lobes and may be
complicated by empyema. E coli bacteremia precedes pneumonia and is usually due to another
focus of E coli infection in the urinary or GI tract.

Intra-abdominal infections
E coli intra-abdominal infections often result from a perforated viscus (eg, appendix,
diverticulum) or may be associated with intra-abdominal abscess, cholecystitis, and ascending
cholangitis. Patients with diabetes mellitus are also at high risk of developing pylephlebitis of the
portal vein and liver abscesses. Escherichia coliliver abscess is seen in the image below.
Escherichia coli liver abscess.
Intra-abdominal abscesses are usually polymicrobial and can be caused by spontaneous or
traumatic GI tract perforation or after anastomotic disruption with spillage of colon contents and
subsequent peritonitis. They can be observed in the postoperative period after anastomotic
disruption. Abscesses are often polymicrobial, and E coli is one of the more common gram-
negative bacilli observed together with anaerobes.
Cholecystitis and cholangitis result from obstruction of the biliary system from biliary stone or
sludge, leading to stagnation and bacterial growth from the papilla or portal circulation. When
bile flow is obstructed, colonic organisms, including E coli, colonize the jejunum and duodenum.
Interestingly, partial obstruction is more likely than complete obstruction to result in infection,
bacteremia, bactibilia, and gallstones.

Enteric infections
As a cause of enteric infections, 6 different mechanisms of action of 6 different varieties of E
coli have been reported. Enterotoxigenic E coli (ETEC) is a cause of traveler's diarrhea.
Enteropathogenic E coli (EPEC) is a cause of childhood diarrhea. Enteroinvasive E coli (EIEC)
causes a Shigella -like dysentery. Enterohemorrhagic E coli (EHEC) causes hemorrhagic colitis
or hemolytic-uremic syndrome (HUS). Enteroaggregative E coli(EAggEC) is primarily
associated with persistent diarrhea in children in developing countries, and enteroadherent E
coli (EAEC) is a cause of childhood diarrhea and traveler's diarrhea in Mexico and North Africa.
ETEC, EPEC, EAggEC, and EAEC colonize the small bowel, and EIEC and EHEC
preferentially colonize the large bowel prior to causing diarrhea.
Shiga toxin–producing E coli (STEC) is among the most common causes of foodborne diseases.
This organism is responsible for several GI illnesses, including nonbloody and bloody diarrhea.
Patients with these diseases, especially children, may be affected by neurologic and renal
complications, including HUS. Strains of STEC serotype O157-H7 have caused numerous
outbreaks and sporadic cases of bloody diarrhea and HUS.
Kappeli et al looked at 97 non-O157 STECstrains in patients with diarrhea and found that HUS
developed in 40% of patients; serotype O26:H11/H was most often associated with this
syndrome. [1] Although strains associated with HUS were more likely to harbor STX 2
and EAE compared with those associated with bloody diarrhea , only 5 of the 8 patients with
HUS had the STX2 gene; among the 3 patients with EAE -negative, STX2 -negative strains,
only STX1 or STX1 and EHXAcaused the HUS.

Urinary tract infections

The urinary tract is the most common site of E coliinfection, and more than 90% of all
uncomplicated UTIs are caused by E coli infection. The recurrence rate after a first E
coli infection is 44% over 12 months. E coli UTIs are caused by uropathogenic strains of E
coli. E colicauses a wide range of UTIs, including uncomplicated urethritis/cystitis, symptomatic
cystitis, pyelonephritis, acute prostatitis, prostatic abscess, and urosepsis. Uncomplicated cystitis
occurs primarily in females who are sexually active and are colonized by a uropathogenic strain
of E coli. Subsequently, the periurethral region is colonized from contamination of the colon, and
the organism reaches the bladder during sexual intercourse.
Uropathogenic strains of E coli have an adherence factor called P fimbriae, or pili, which binds
to the P blood group antigen. These P fimbriae mediate the attachment of E coli to uroepithelial
cells. Thus, patients with intestinal carriage of E coli that contains P fimbriae are at greater risk
of developing UTI than the general population. Complicated UTI and pyelonephritis are
observed in elderly patients with structural abnormalities or obstruction such as prostatic
hypertrophy or neurogenic bladders or in patients with urinary catheters. Escherichia coli right
pyelonephritis is seen in the image below.
Escherichia coli right pyelonephritis.
E coli bacteremia is usually associated with UTIs, especially in cases of urinary tract obstruction
of any cause. The systemic reaction to endotoxin (cytokines) or lipopolysaccharides can lead
to disseminated intravascular coagulation and death. E coli is a leading cause of nosocomial
bacteremia from a GI or genitourinary source.

Other infections
Other miscellaneous E coli infections include septic arthritis, endophthalmitis,
suppurative thyroiditis, sinusitis, osteomyelitis, endocarditis, and skin and soft-tissue infections
(especially in patients with diabetes).

History

Acute bacterial meningitis

Newborns with E coli meningitis present with fever and failure to thrive or abnormal neurologic
signs. Other findings in neonates include jaundice, decreased feeding, periods of apnea, and
listlessness.
Patients younger than 1 month present with irritability, lethargy, vomiting, lack of appetite, and
seizures.
Those older than 4 months have neck rigidity, tense fontanels, and fever.
Older children and adults with acute E coli meningitis develop headache, vomiting, confusion,
lethargy, seizures, and fever.
In rare cases, persons with a history of open CNS trauma or multiple neurological procedures
develop S stercoralis hyperinfection.
Because patients who have undergone neurosurgery frequently have headaches, nuchal rigidity,
and a decreased level of consciousness secondary to the surgery, signs may be difficult to
interpret.
The differential diagnoses of acute E coli meningitis include sepsis, seizure disorder, brain
abscess, ruptured aneurysm, and neonatal tetanus.

Pneumonia
Patients with E coli pneumonia usually present with fever, shortness of breath, increased
respiratory rate, increased respiratory secretions, and crackles upon auscultation.
Findings include bronchopneumonia on chest radiography, commonly in the lower lobes. Many
patients are intubated and have fever, an increased respiratory rate, and increased respiratory
secretions.
The differential diagnoses of E coli pneumonia include congestive heart failure and pulmonary
embolism. Other pneumonias caused by gram-negative bacilli are difficult to distinguish
clinically.
Intra-abdominal infections
Patients with E coli cholecystitis or cholangitis develop right upper quadrant (RUQ) pain, fever,
and jaundice. In severe cases, hypotension and confusion also develop. Cholecystitis manifests
with fever (>102°F). Cholangitis manifests with fever (>102°F), shaking chills, and RUQ pain
and can be complicated by hepatic abscess. Amebic liver abscess, Echinococcus cyst,
and Klebsiella and Enterococcus infections are difficult to distinguish clinically. Anaerobes are
observed in patients with diabetes and acute acalculous cholecystitis.
Patients with E coli intra-abdominal abscesses may have low-grade fever, but the spectrum of
clinical presentations ranges from nonspecific abdominal examination findings to frank septic
shock. Peritonitis manifests as localized pain with rebound and fever. The presentation ranges
from low-grade fever with abdominal tenderness, weakness, malaise, and anorexia to hypoxemia
and hypotension. The infection is usually polymicrobial with E coli and other gram-negative
bacilli and anaerobes. The differential diagnoses include retroperitoneal hematoma and septic
thrombophlebitis.

Enteric infections
Patients with E coli traveler's diarrhea (ie, watery nonbloody diarrhea; caused by
enterotoxigenic E coli [ETEC] or enteroaggregative E coli[EAggEC]) may appear to be
dehydrated. Traveler's diarrhea is observed in young healthy travelers to tropical countries and is
watery diarrhea without polymorphonuclear (PMN) leukocytes. The differential diagnoses of E
coli traveler's diarrhea include rotavirus infection, Norwalk virus infection, Salmonella infection,
and Campylobacterdiarrhea.
Patients with E coli childhood diarrhea (ie, watery nonbloody diarrhea; caused by EAggEC,
enteroadherent E coli [EAEC], or enteropathogenic E coli [EPEC]) may also appear to be
dehydrated. These infections produce a noninflammatory watery diarrhea observed especially in
children. The differential diagnoses of E coli childhood diarrhea include Vibrio
cholerae infection and Rotavirus infection.
In May, June, and July, 2011 an outbreak of gastroenteritis caused by Shiga-toxin–producing E
coli was seen in Germany. The majority of patients were adults and 22% of the cases developed
hemolytic–uremic syndrome The outbreak strain was typed as an enteroaggregative Shiga-toxin–
producing E coli O104:H4, producing extended-spectrum beta-lactamase. The consumption of
sprouts was identified as the most likely vehicle of infection. This outbreak was different as it
was caused by EAggEC that produced a Shiga toxin and it exemplifies the threat posed by
foodborne pathogens with their propensity to cause large common-source outbreaks. [2, 3]
Patients with E coli dysentery (caused by enteroinvasive E coli [EIEC] or enterohemorrhagic E
coli [EHEC]) have fever, bloody diarrhea, and dehydration. Intestinal mucosa produces a
significant inflammatory response. Clinically, patients with E coli dysentery present with fever
and have blood and PMN leukocytes in their stool. The differential diagnoses of E coli dysentery
include shigellosis and amebic dysentery.
Patients with E coli HUS (caused by EHEC) have fever, bloody diarrhea, dehydration,
hemolysis, thrombocytopenia, and uremia requiring dialysis. Symptoms of E coli HUS range
from asymptomatic to nonbloody diarrhea to bloody diarrhea, renal failure, microangiopathic
hemolytic anemia, thrombocytopenia, and CNS manifestations. The differential diagnoses of E
coli HUS include Shigella infections, Clostridium difficile enterocolitis, ulcerative colitis/Crohn
disease, ischemic colitis, diverticulosis, and appendicitis.
Urinary tract infections
Acute E coliurethral syndrome manifests as low-grade fever and dysuria. Patients present with
dysuria, increased frequency, and urgency, and they have colony counts. S
saprophyticus infection is observed in 5-10% of cases, especially in sexually active women,
associated with alkaline pH and microscopic hematuria. Less commonly, patients have Proteus
mirabilis, Klebsiella, or Enterococcusinfections. Approximately 15% of cases are culture-
negative; these are due to Chlamydia trachomatis, Ureaplasma urealyticum, or Mycoplasma
hominis infection.
Patients with symptomatic E coli UTI have dysuria and may have low-grade fever.
Patients with E coli pyelonephritis or complicated UTI present with localized flank or low back
pain, high fever (>102°F), and urinary frequency and urgency. Findings also include rigors,
sweating, headache, nausea, and vomiting. It can be complicated by necrotizing intrarenal
or perinephric abscess, which manifests as a bulging flank mass or pyelonephritis that does not
respond to antibiotics. Patients with diabetes or urinary tract obstruction can also develop
bacteremia and septicemia. The differential diagnoses include psoas abscess appendicitis, ectopic
pregnancy, and ruptured ovarian cyst.
Patients with E coliacute prostatitis or prostatic abscess have chills, sudden fever (>102°F), and
perineal and back pain with a tender, swollen, indurated, and hot prostate. Acute prostatitis also
manifests as dysuria, urgency, and frequent voiding. Some patients may have myalgia, urinary
retention, malaise, and arthralgia. If the patient does not respond to antibiotics, consider prostatic
abscess and confirm it with imaging studies. Treatment consists of open surgical or percutaneous
drainage.
Patients with E coli prostatic abscess, which manifests as a complication of acute prostatitis,
have a high fever despite adequate antimicrobial therapy and fluctuance of the prostate upon
rectal examination.
The differential diagnoses of E coli acute prostatitis or prostatic abscess can include chronic
bacterial prostatitis, which is usually asymptomatic; some patients may have frequency, dysuria,
and nocturia with pain and discomfort in the perineal, suprapubic, penile, scrotal, or groin region.
Also included are infected prostatic calculi, which can cause recurrent UTIs and should be
surgically removed. Finally, nonbacterial prostatitis is also a differential diagnostic possibility
and manifests as perineal, suprapubic scrotal, low back, or urethral tip pain.
Additionally, patients with E coli renal abscess present with fever, pleuritic chest pain secondary
to diaphragmatic irritation, and flank pain, with or without a palpable abdominal mass. [2]
Physical

Acute bacterial meningitis

E coli is a common cause of meningitis in newborns and is associated most frequently with
prematurity.
E coli meningitis can be acquired during birth or can develop secondarily after infection in
another body site, such as in cases of omphalitis, upper respiratory tract infection, or infected
circumcision wound.
In adults, E coli meningitis is not uncommon in those who have undergone multiple neurological
procedures or who have had open CNS trauma.
Immunosuppressed patients receiving corticosteroid therapy and those with S
stercoralis hyperinfection are also at risk for E coli meningitis.
Pneumonia
E coli pneumonia is often preceded by colonization of the upper respiratory tract (eg,
nasopharynx).
Community-acquired E coli pneumonia has been reported in rare cases.
Intra-abdominal infections
Along with Enterococcus faecalis and Klebsiella species, E coli is one of the most common
organisms associated with cholecystitis/cholangitis and intra-abdominal abscesses, as part of
polymicrobial flora including anaerobes.
E coli cholecystitis/cholangitis manifests as the classic Charcot triad of fever, pain, and jaundice
in 70% of cases. Fever is the most common finding (95%). RUQ pain and jaundice may be
absent if no obstruction is present.
In late stages, hypotension, confusion, and renal failure are observed.
Liver abscess can develop as a complication of a E coli biliary tract infection.
The findings of E coli intra-abdominal abscesses are less conspicuous than those of diffuse
peritonitis. The patient may have only low-grade fever, generalized malaise, and anorexia. In the
postoperative patient who may have a distended and tender abdomen, clinical diagnosis of E
coli intra-abdominal abscess may be difficult.

Enteric infections
Traveler's diarrhea usually occurs in persons from industrialized countries who visit tropical or
subtropical regions and develop abdominal cramps and frequent explosive bowel movements 1-2
days after exposure to contaminated food or water.
E coli enterotoxin acts on the GI mucosa, leading to an outpouring of copious fluid from the
small bowel.
The symptoms usually last 3-4 days and are self-limited.
Large fluid loss may result in dehydration.
EIEC infections are rare and manifest as bloody diarrheal stool containing PMN leukocytes.
Patients usually have fever, abdominal cramping, and tenesmus lasting 5-7 days.
Childhood diarrhea is due to EPEC strains and usually occurs in underdeveloped countries or
nursery outbreaks. The volume of diarrhea is less than that with ETEC strains, and no
inflammatory cells are found in the diarrheal fluid. The child may experience fever, and diarrhea
lasts longer than 2 weeks in some cases.
Infection with EHEC strains of the serotype 0157:H7 begin as watery diarrhea followed by
grossly bloody stool without inflammatory PMN cells and results in HUS in 10% of cases,
characterized by hemolysis, thrombocytopenia, uremia (possibly requiring dialysis), and death in
some cases.
EAggEC and EAEC cause clinical illnesses that are not yet well characterized and are associated
with persistent diarrhea in children.

Urinary tract infections

E coli is the leading cause of community-acquired and nosocomial UTI.
Females are predisposed to UTI because of their anatomy and changes during sexual maturation,
pregnancy, and childbirth.
Young boys with posterior urethral valves are also predisposed to UTIs, as are elderly men with
prostatic hypertrophy.
Other risk factors include catheterization or mechanical manipulation, obstruction, or diabetes.
Patients with E coli UTI present with a wide spectrum of symptoms, ranging from asymptomatic
cystitis to pyelonephritis/perinephric abscess.
Urethral syndrome is a term used to describe symptoms of dysuria with colony counts less than
100,000 colony-forming units/mL of urine.
Uncomplicated E coli acute cystitis may manifest as low-grade fever, dysuria, and increased
urinary frequency.
Acute pyelonephritis manifests as high-grade fever (>102°F) and costovertebral tenderness.
Acute prostatitis manifests as a sudden onset of fever and chills with perineal and low back pain.
Perinephric abscess may manifest as a bulging flank mass. GI symptoms such as nausea and
vomiting are more likely in elderly persons. Patients with bacteremia secondary to an obstructed
urinary catheter may present with decreased urine output.
Prostatic abscess can occur as a complication of acute prostatitis, notably in patients with
diabetes mellitus, and should be considered in patients with acute prostatitis or UTI that is not
improving with adequate antimicrobial therapy.

Other infections
E coli bacteremia can lead to septic shock, manifesting as hypotension and fever (in some cases,
with hypothermia rather than fever). It may be complicated by uremia, hepatic failure, acute
respiratory distress syndrome, stupor or coma, and death. Non–life-threatening E colibacteremia
may manifest as a sudden onset of fever and chills, tachycardia, tachypnea, and mental
confusion. In cases of E coli UTI with urinary tract obstruction, bacteremia or septicemia may
ensue.
A retrospective study determined risk factors for mortality in patients with fluoroquinolone-
resistant E coli. Results show fluoroquinolone resistance, cirrhosis, and cardiac dysfunction
independently predicted mortality. [4]
Several cases of E coliendophthalmitis have been reported in patients with diabetes who have
UTI or pyelonephritis. [5]

Klebsiella
Background
The genus Klebsiella belongs to the tribe Klebsiellae, a member of the family
Enterobacteriaceae. The organisms are named after Edwin Klebs, a 19th century German
microbiologist. Klebsiellae are nonmotile, rod-shaped, gram-negative bacteria with a prominent
polysaccharide capsule. This capsule encases the entire cell surface, accounts for the large
appearance of the organism on gram stain, and provides resistance against many host defense
mechanisms.
Members of the Klebsiella genus typically express 2 types of antigens on their cell surface. The
first is a lipopolysaccharide (O antigen); the other is a capsular polysaccharide (K antigen). Both
of these antigens contribute to pathogenicity. About 77 K antigens and 9 O antigens exist. The
structural variability of these antigens forms the basis for classification into various serotypes.
The virulence of all serotypes appears to be similar.
Three species in the genus Klebsiella are associated with illness in humans: Klebsiella
pneumoniae, Klebsiella oxytoca, and Klebsiella granulomatis. Organisms previously known
as Klebsiella ozaenae and Klebsiella rhinoscleromatis are considered nonfermenting subspecies
of K pneumoniae that have characteristic clinical manifestations. With those exceptions, strains
within this genus ferment lactose, most produce highly mucoid colonies on plates because of the
production of a luxuriant polysaccharide capsule, and all are nonmotile. [1] In recent years,
klebsiellae have become important pathogens in nosocomial infections. [2] See the image below.
This scanning electron micrograph (SEM) reveals some of the ultrastructural morphologic
features of Klebsiella pneumoniae. Courtesy of CDC/Janice Carr.

Pathophysiology
Host defense against bacterial invasion depends on phagocytosis by polymorphonuclear
granulocytes and the bactericidal effect of serum, mediated in large part by complement proteins.
Both classic-pathway and alternate-pathway complement activation have been described, but the
latter, which does not require the presence of immunoglobulins directed against bacterial
antigens, appears to be the more active pathway in K pneumoniae infections.
Recent data from preclinical studies suggest a role for neutrophil myeloperoxidase and
lipopolysaccharide-binding protein in host defense against K pneumoniaeinfection. Neutrophil
myeloperoxidase is thought to mediate oxidative inactivation of elastase, an enzyme implicated
in the pathogenesis of various tissue-destroying diseases. Lipopolysaccharide-binding protein
facilitates transfer of bacterial cell wall components to inflammatory cells. Investigators showed
higher rates of infection in experimental mice deficient in the genes that control expression of
these 2 agents.
The bacteria overcome innate host immunity through several means. They possess a
polysaccharide capsule, which is the main determinant of their pathogenicity. The capsule is
composed of complex acidic polysaccharides. Its massive layer protects the bacterium from
phagocytosis by polymorphonuclear granulocytes. In addition, the capsule prevents bacterial
death caused by bactericidal serum factors. This is accomplished mainly by inhibiting the
activation or uptake of complement components, especially C3b. The bacteria also produce
multiple adhesins. These may be fimbrial or nonfimbrial, each with distinct receptor specificity.
These help the microorganism to adhere to host cells, which is critical to the infectious process.
Lipopolysaccharides (LPS) are another bacterial pathogenicity factor. They are able to activate
complement, which causes selective deposition of C3b onto LPS molecules at sites distant from
the bacterial cell membrane. This inhibits the formation of the membrane attack complex (C5b-
C9), which prevents membrane damage and bacterial cell death.
Availability of iron increases host susceptibility to K pneumoniae infection. Bacteria are able to
compete effectively for iron bound to host proteins because of the secretion of high-affinity, low
molecular weight iron chelators known as siderophores. This is necessary because most host iron
is bound to intracellular and extracellular proteins. In order to deprive bacteria of iron, the host
also secretes iron-binding proteins.
Epidemiology of Klebsiellae
Klebsiellae are ubiquitous in nature. In humans, they may colonize the skin, pharynx, or
gastrointestinal tract. They may also colonize sterile wounds and urine. Carriage rates vary with
different studies. Klebsiellae may be regarded as normal flora in many parts of the colon and
intestinal tract and in the biliary tract. Oropharyngeal carriage has been associated with
endotracheal intubation, impaired host defenses, and antimicrobial use.
K pneumoniae and K oxytoca are the 2 members of this genus responsible for most human
infections. They are opportunistic pathogens found in the environment and in mammalian
mucosal surfaces. The principal pathogenic reservoirs of infection are the gastrointestinal tract of
patients and the hands of hospital personnel. Organisms can spread rapidly, often leading to
nosocomial outbreaks.
Infection with Klebsiella organisms occurs in the lungs, where they cause destructive changes.
Necrosis, inflammation, and hemorrhage occur within lung tissue, sometimes producing a thick,
bloody, mucoid sputum described as currant jelly sputum. The illness typically affects middle-
aged and older men with debilitating diseases such as alcoholism, diabetes, or chronic
bronchopulmonary disease. This patient population is believed to have impaired respiratory host
defenses. The organisms gain access after the host aspirates colonizing oropharyngeal microbes
into the lower respiratory tract.
Klebsiellae have also been incriminated in nosocomial infections. Common sites include the
urinary tract, lower respiratory tract, biliary tract, and surgical wound sites. The spectrum of
clinical syndromes includes pneumonia, bacteremia, thrombophlebitis, urinary tract infection
(UTI), cholecystitis, diarrhea, upper respiratory tract infection, wound infection, osteomyelitis,
and meningitis. The presence of invasive devices, contamination of respiratory support
equipment, use of urinary catheters, and use of antibiotics are factors that increase the likelihood
of nosocomial infection with Klebsiellaspecies. Sepsis and septic shock may follow entry of
organisms into the blood from a focal source.
Klebsiella granulomatis (formerly Calymmatobacterium granulomatis) is a fastidious member of
the genus that causes chronic genital ulcerative disease also known as granuloma inguinale or
donovanosis. It is a relatively rare disease in the United States, with fewer than 100 cases
reported annually. It has long been a recognized cause of genital ulceration in parts of India,
Papua New Guinea, the Caribbean, and South America (particularly Brazil). Fortunately, the
incidence of the disease has decreased in recent years.
Rhinoscleroma and ozena are 2 other infections caused by Klebsiella species. These diseases are
rare. Rhinoscleroma is a chronic inflammatory process involving the nasopharynx, whereas
ozena is a chronic atrophic rhinitis characterized by necrosis of nasal mucosa and mucopurulent
nasal discharge.
K oxytoca has been implicated in neonatal bacteremia, especially among premature infants and in
neonatal intensive care units. Increasingly, the organism is being isolated from patients with
neonatal septicemia.
Extensive use of broad-spectrum antibiotics in hospitalized patients has led to both increased
carriage of klebsiellae and, subsequently, the development of multidrug-resistant strains that
produce extended-spectrum beta-lactamase (ESBL). These strains are highly virulent, show
capsular type K55, and have an extraordinary ability to spread. Most outbreaks are due to a
single clone or single gene; the bowel is the major site of colonization with infection of the
urinary tract, respiratory tract, and wounds. Bacteremia and significant increased mortality have
resulted from infection with these species.
In addition to prior antibiotic use, risk factors for infection include the presence of an indwelling
catheter, feeding tube, or central venous catheter; poor health status; and treatment in an
intensive care unit or nursing home. Acquisition of these species has become a major problem in
most hospitals because of resistance to multiple antibiotics and potential transfer of plasmids to
other organisms.
Carbapenem-resistant Enterobacteriaceae (CRE), which are sometimes known as K
pneumoniae carbapenemase (KPC) and New Delhi metallo-beta-lactamase (NDM), are a family
of bacteria that are difficult to treat because of their high levels of resistance to antibiotics. Some
CRE bacteria have become resistant to most available antibiotics and cause mortality rates of up
to 50%.

Community-acquired pneumonia
Lobar pneumonia differs from other pneumonias in that it is associated with destructive changes
in the lungs. It is a very severe illness with a rapid onset and often-fatal outcome despite early
and appropriate antimicrobial treatment.
Patients typically present with an acute onset of high fever and chills; flulike symptoms; and
productive cough with an abundant, thick, tenacious, and blood-tinged sputum sometimes called
currant jelly sputum.
An increased tendency exists toward abscess formation, cavitation, empyema, and pleural
adhesions.
Most pulmonary diseases caused by K pneumoniae are in the form of bronchopneumonia or
bronchitis. These infections are usually hospital-acquired and have a more subtle presentation.

Urinary tract infection

Klebsiellae UTIs [5] are clinically indistinguishable from UTIs caused by other common
organisms.
Clinical features include frequency, urgency, dysuria, hesitancy, low back pain, and suprapubic
discomfort. Systemic symptoms such as fever and chills are usually indicative of a concomitant
pyelonephritis or prostatitis.

Nosocomial infection
Important manifestations of klebsiellae infection in the hospital setting include UTI, pneumonia,
bacteremia, wound infection, cholecystitis, and catheter-associated bacteriuria. The presence of
invasive devices in hospitalized patients greatly increases the likelihood of infection. Patients
with these infections have similar presentations to those with infections caused by other
organisms.
Other nosocomial infections in which klebsiellae may also be implicated include cholangitis,
meningitis, endocarditis, and bacterial endophthalmitis. The latter occurs especially in patients
with liver abscesses [6] and diabetes. These infectious presentations are relatively uncommon.

Rhinoscleroma and ozena

K rhinoscleromatis and K ozaenae cause rhinoscleroma and ozena, respectively. Both are rare in
the United States and are associated with upper respiratory infection.
Rhinoscleroma is a chronic granulomatous infection. Patients present with a purulent nasal
discharge with crusting and nodule formation that leads to respiratory obstruction. Diagnosis is
aided by histology findings and positive results from blood culture.
Ozena is a primary atrophic rhinitis that often occurs in elderly persons. Common symptoms
include nasal congestion and a constant nasal bad smell. Patients also may complain of headache
and symptoms attributable to chronic sinusitis. Unlike rhinoscleroma, nasal congestion is not a
prominent feature.

Chronic genital ulcerative disease

K granulomatis infection can result in granuloma inguinale or donovanosis, although these are
uncommon in developed temperate countries. The mode of transmission is uncertain but is
believed to be sexually transmitted. The incubation period is 1-3 weeks.
Ulcerative infection is likely transmitted by contact with microabraded skin. Nonulcerative
infection is probably transmitted transepithelially.
Coinfection with other sexually transmitted diseases (STDs) is common.
Klebsiella chronic genital ulcerative disease presents as a firm papule or subcutaneous nodule
that later ulcerates. An ulcerogranulomatous presentation is most common and is characterized
as a beefy red ulcer. A hypertrophic or verrucous presentation may mimic condylomata
acuminate. A necrotic presentation is characterized by a deep ulcer. Sclerotic and cicatricial
presentations are rare.
Diagnosis is based on clinical suspicion. Direct microscopy shows intracytoplasmic bipolar
staining inclusion bodies (Donovan bodies).

Colonization
Differentiating nosocomial colonization from infection presents a formidable challenge in
clinical practice. It is a common problem in patients with indwelling catheters.
Duration of catheterization is the most important risk factor for the development of bacteriuria.
Keeping catheter systems closed and removing catheters as soon as possible are ways to prevent
development of bacteriuria.
Most catheter-related UTIs are asymptomatic; the usual complaints of frequency, urgency,
dysuria, hesitancy, low back pain, and suprapubic discomfort typically are absent. Therefore,
demonstration of bacteriuria is necessary to make a diagnosis. A density of 100,000 colony-
forming units per milliliter is usually required to make a diagnosis. Concomitant presence of
pyuria is usually present in patients with catheter-associated infection as opposed to those with
colonization.
In general, the presence of symptoms in conjunction with bacteriological evidence of infection
helps distinguish infection, in which organisms cause disease, from colonization, in which
organisms coexist without causing harm.

Physical
Klebsiella pneumonia characteristically affects one of the upper lobes of the lung, although
infection of the lower lobes is not uncommon.
Examination of patients with community-acquired pneumonia usually reveals unilateral chest
signs, predominantly in the upper lobes. When these signs are observed in a patient such as
described in History, the diagnosis of Klebsiella pneumonia is strongly suggested.
Clinical signs observed in patients with extrapulmonary disease depend on the organ system
involved. In cases of nosocomial infections, physical examination should include a search for
factors that predispose the individual to the development of such infections. These should
include inspection for the presence and duration of invasive devices, wounds, and burn sites.

Causes
Host factors that lead to colonization and infection include the following:
 Hospitalization (especially admission to an intensive care unit)
 Immunocompromised states (eg, diabetes, alcoholism)
 Antimicrobial therapy
 Prolonged use of invasive medical devices
 Inadequate infection control practices
 Severe illness, including major surgery
The organism gains access to the body either by direct inoculation through breached epithelial
surfaces or following aspiration of oropharyngeal organisms.

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 pneumoniaeshould 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. [10]
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. [54]
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
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. [11]
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. [1]
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
pneumoniaeinfection. 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 oxytocabacteremia 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.

What are Klebsiellae?

The genus Klebsiella belongs to the tribe Klebsiellae, a member of the family
Enterobacteriaceae. The organisms are named after Edwin Klebs, a 19th century German
microbiologist. Klebsiellae are nonmotile, rod-shaped, gram-negative bacteria with a prominent
polysaccharide capsule. This capsule encases the entire cell surface, accounts for the large
appearance of the organism on gram stain, and provides resistance against many host defense
mechanisms.

Which antigens do members of the Klebsiella genus typically express?

Members of the Klebsiella genus typically express 2 types of antigens on their cell surface. The
first is a lipopolysaccharide (O antigen); the other is a capsular polysaccharide (K antigen). Both
of these antigens contribute to pathogenicity. About 77 K antigens and 9 O antigens exist. The
structural variability of these antigens forms the basis for classification into various serotypes.
The virulence of all serotypes appears to be similar.
Which species of Klebsiellae are pathogenic in humans?
Three species in the genus Klebsiella are associated with illness in humans: Klebsiella
pneumoniae, Klebsiella oxytoca, and Klebsiella granulomatis. Organisms previously known
as Klebsiella ozaenae and Klebsiella rhinoscleromatis are considered nonfermenting subspecies
of K pneumoniae that have characteristic clinical manifestations. With those exceptions, strains
within this genus ferment lactose, most produce highly mucoid colonies on plates because of the
production of a luxuriant polysaccharide capsule, and all are nonmotile. [1] In recent years,
klebsiellae have become important pathogens in nosocomial infections.

What are rhinoscleroma and ozena?

Rhinoscleroma and ozena are 2 other infections caused by Klebsiella species. These diseases are
rare. Rhinoscleroma is a chronic inflammatory process involving the nasopharynx, whereas
ozena is a chronic atrophic rhinitis characterized by necrosis of nasal mucosa and mucopurulent
nasal discharge.

Proteus

Background
Proteus species are part of the Enterobacteriaceae family of gram-negative
bacilli. Proteus organisms are implicated as serious causes of infections in humans, along
with Escherichia, Klebsiella, Enterobacter, and Serratia species.
Proteus species are most commonly found in the human intestinal tract as part of normal human
intestinal flora, along with Escherichia coli and Klebsiella species, of which E coli is the
predominant resident. Proteus is also found in multiple environmental habitats, including long-
term care facilities and hospitals. In hospital settings, it is not unusual for gram-negative bacilli
to colonize both the skin and oral mucosa of both patients and hospital personnel. Infection
primarily occurs from these reservoirs. However, Proteus species are not the most common
cause of nosocomial infections.
Proteus mirabilis causes 90% of Proteus infections and can be considered a community-acquired
infection. Proteus vulgaris and Proteus penneri may be isolated from individuals in long-term
care facilities and hospitals and from patients with underlying diseases or compromised immune
systems.
Patients with recurrent infections, those with structural abnormalities of the urinary tract, those
who have had urethral instrumentation, and those whose infections were acquired in the hospital
have an increased frequency of infection caused by Proteus and other organisms (eg, Klebsiella,
Enterobacter, Pseudomonas,enterococci, staphylococci).

Pathophysiology
Proteus species possess an extracytoplasmic outer membrane, a feature shared with other gram-
negative bacteria. In addition, the outer membrane contains a lipid bilayer, lipoproteins,
polysaccharides, and lipopolysaccharides.
Infection depends on the interaction between the infecting organism and the host defense
mechanisms. Various components of the membrane interplay with the host to determine
virulence. Inoculum size is important and has a positive correlation with the risk of infection.
Certain virulence factors have been identified in bacteria. The first step in the infectious process
is adherence of the microbe to host tissue. Fimbriae facilitate adherence and thus enhance the
capacity of the organism to produce disease. E coli, P mirabilis, and other gram-negative
bacteria contain fimbriae (ie, pili), which are tiny projections on the surface of the bacterium.
Specific chemicals located on the tips of pili enable organisms to attach to selected host tissue
sites (eg, urinary tract endothelium). The presence of these fimbriae has been demonstrated to be
important for the attachment of P mirabilis to host tissue.
The attachment of Proteus species to uroepithelial cells initiates several events in the mucosal
endothelial cells, including secretion of interleukin 6 and interleukin 8. Proteus organisms also
induce apoptosis and epithelial cell desquamation. Bacterial production of urease has also been
shown to increase the risk of pyelonephritis in experimental animals. Urease production, together
with the presence of bacterial motility and fimbriae, may favor the production of upper urinary
tract infections (UTIs) by organisms such as Proteus.
Enterobacteriaceae (of which Proteus is a member) and Pseudomonas species are the
microorganisms most commonly responsible for gram-negative bacteremia. When these
organisms invade the bloodstream, endotoxin, a component of gram-negative bacterial cell walls,
apparently triggers a cascade of host inflammatory responses and leads to major detrimental
effects. Because Proteus and Pseudomonas organisms are gram-negative bacilli, they can cause
gram-negative endotoxin-induced sepsis, resulting in systemic inflammatory response
syndrome (SIRS), which carries a mortality rate of 20%-50%.
Although other organisms can trigger a similar response, it is useful to consider gram-negative
bacteremia as a distinct entity because of its characteristic epidemiology, pathogenesis,
pathophysiology, and treatment. The presence of the sepsis syndrome associated with a UTI
should raise the possibility of urinary tract obstruction. This is especially true of patients who
reside in long-term care facilities, who have long-term indwelling urethral catheters, or who have
a known history of urethral anatomic abnormalities.
The ability of Proteus organisms to produce urease and to alkalinize the urine by hydrolyzing
urea to ammonia makes it effective in producing an environment in which it can survive. This
leads to precipitation of organic and inorganic compounds, which leads to struvite
stoneformation. Struvite stones are composed of a combination of magnesium ammonium
phosphate (struvite) and calcium carbonate-apatite.
Struvite stone formation can be sustained only when ammonia production is increased and the
urine pH is elevated to decrease the solubility of phosphate. Both of these requirements can
occur only when urine is infected with a urease-producing organism such as Proteus. Urease
metabolizes urea into ammonia and carbon dioxide: Urea → 2NH3 + CO2. The
ammonia/ammonium buffer pair has a pK of 9.0, resulting in the combination of highly alkaline
urine rich in ammonia.
Symptoms attributable to struvite stones are uncommon. More often, women present with UTI,
flank pain, or hematuria and are found to have a persistently alkaline urine pH (>7.0).

History
Approximately 95% of UTIs occur when bacteria ascend through the urethra and the bladder.
Complicated UTIs occur with instrumentation (including Foley catheters), obstruction, calculi,
or neurogenic bladder. These carry a higher risk for complications such as hospitalization and
sepsis.
Sexually active women are at greater risk for UTIs. The same is true for men, although to a lesser
degree.
Other predisposing factors for UTIs are men who have unprotected anal intercourse, an
uncircumcised penis, unprotected vaginal intercourse, and/or CD4 count less than 200/µL.
Although infrequent, chronic prostatitis should be considered in males with a history of recurrent
UTIs. Obstructive symptoms are transient but may progress to infect the bladder because of poor
bladder emptying.
Frequent and unexplained incidents of renal calculi may be indicative of a
chronic Proteus infection. Multiple magnesium ammonium phosphate crystals are present in the
urine sediment along with radio dense renal calculus. (This calculus is less radio dense than
calcium oxalate.) This results in formation and precipitation of struvite crystals, a predominant
component of urinary calculi and encrustations on urinary catheters.

Physical
Patients may present with urethritis, cystitis, prostatitis, or pyelonephritis. Chronic, recurring
stones may be an indication of chronic infection.

Urethritis
Symptoms of urethritis are usually mild and may be dismissed by the patient.
Women present with dysuria, pyuria, and increased frequency of urination.
Presenting symptoms in males are usually mild and may include urethral discharge.

Cystitis
Signs and symptoms of cystitis tend to be more prominent compared to those of urethritis.
In both men and women, symptoms are of sudden onset.
They include dysuria, increased frequency, urgency, suprapubic pain, back pain, small volumes,
concentrated appearance, and hematuria. If the patient is febrile, this could be a sign of
bacteremia and impending sepsis. These symptoms may not be present if the patient has an
indwelling catheter.

Prostatitis
Prostatitis is obviously limited to men and occurs more acutely than cystitis. This becomes more
common as men age.
In addition to symptoms of cystitis, patients with prostatitis may present with fever and chills.
Perianal pain and various symptoms of urinary tract obstruction may be present. The prostate
may be tender and diffusely swollen.
Pyelonephritis
Pyelonephritis can be considered a progression of disease, and symptoms are therefore more
profound. Sepsis can develop quickly, especially in elderly patients or those with a compromised
immune system.
Symptoms of urethritis and cystitis may or may not be present.
Defining symptoms of pyelonephritis include flank pain, nausea and vomiting, costovertebral
angle tenderness, fever, and, rarely, a palpable and tender kidney. Hematuria and pyuria are
frequently encountered.

Causes
Hospital-acquired infections are usually caused by interruption of the closed sterile system by
hospital personnel.
Proteus species also cause sepsis neonatorum and bacteremia with fever and neutropenia.
Proteus species are also involved in synergistic nonclostridial anaerobic myonecrosis, which
may involve subcutaneous tissue, fascia, and muscle. This condition is caused by combinations
of other aerobic gram-negative bacilli (E coli or Klebsiella or Enterobacterspecies) and
anaerobes. Surgical evaluation and intervention is critical to successful treatment.

Laboratory Studies
Proteus organisms are easily recovered through routine laboratory cultures. Most strains are
lactose-negative and demonstrate characteristic swarming motility on agar plates. Any positive
culture result from an otherwise sterile area should be considered an acute infection if clinical
signs and symptoms are present.
After 24 hours, this inoculated MacConkey agar culture plate cultivated colonial growth of gram-
negative, rod-shaped, and facultatively anaerobic Proteus vulgaris bacteria. Courtesy of the
CDC.
UTIs in symptomatic patients have traditionally been defined by recovering bacteria in large
numbers (ie, >100,000 colony-forming units [CFUs]/mL) on examination. Bacterial counts of
less than 100,000 CFUs/mL may indicate infection in urine samples, especially if obtained
directly from the ureters or renal pelvis, whereas specimens from suprapubic catheters usually
have bacterial counts greater than 100,000 CFUs/mL. However, even small numbers of
organisms may be of true clinical significance in symptomatic patients (eg, women with
the urethral syndrome).
Microscopic bacteriuria is best evaluated through uncentrifuged Gram staining of the urine.
Microscopic bacteriuria is found in 90% of cases when bacterial counts exceed 100,000
CFUs/mL. Detection by microscopy confirms infection, but absence does not exclude infection.
Pyuria is demonstrated in nearly all acute bacterial infections, but its absence calls the diagnosis
into question. The leukocyte esterase dipstick test is a useful alternative to microscopic
examination, but this method is less sensitive than microscopy.
Persistently alkaline urine with a positive Proteus culture finding should prompt an examination
for renal calculi.
Although cultures are the most definitive way of confirming an acute Proteus infection, they are
often prohibitively expensive and take time for complete identification. Cultures are most
effective when patients do not respond to empiric therapy or when they have recurrent
symptoms.