Lecture 04 Infectious Diseases 20/10/2021

Anna Vrtev (sbobinator) – Linda Perissinotto (reviewer)

Infectious Diseases – 04
20/10/2021

In this lecture the professor talks about 2 topics: first we will discuss Urinary Tract Infections (UTI), then
we will see Intra-Abdominal Infections.

Urinary Tract Infections

Urinary tract infections (UTIs) are very frequent, second only to upper/lower respiratory tract infection.

Classification
Based on the anatomical location they are divided into:
Low UTI
- urethritis
- cystitis
- prostatitis
High UTI
- pyelonephritis
- renal abscess
- pararenal abscess

Uncomplicated UTI (usually cystitis)

• Frequent in female
• Favorable prognosis
• Self-limiting in most cases
• Very mild course of the disease
Complicated UTI
• Ratio M/F=1/1 à actually are more frequent in male patients
• Anatomical-functional alteration of the urinary tract (stones, malformations, neoplastic stenosis,
etc.)
• Protracted catheterization

Terminology
• Uncomplicated urinary tract infection (UTI) refers to infection in a structurally and
neurologically normal urinary tract.
• The generally accepted definition of complicated UTI includes infection in the presence of
factors that predispose to persistent or relapsing infection, such as:
- foreign bodies (e.g., calculi, indwelling catheters or other drainage devices);
- obstruction;
- immunosuppression
- renal failure
- renal transplantation
- urinary retention from neurologic disease
- infection in men

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Lecture 04 Infectious Diseases 20/10/2021

- pregnant women
- children
- patients who are hospitalized or in health care–associated settings may be
considered complicated

Pathogenesis
Ascending:
• ascent of bacteria from the anus/urethra to the bladder and kidney
Hematogenic (more frequent):
• renal localization during bacteremia

There are some characteristics of the both the microorganism and the host that may facilitate the
invasion by bacteria in the urinary epithelium:
• Microrganism:
– pili or fimbriae
– bacterial adhesins (glycoproteins) and specific receptors on urothelial cells (glycolipids
with oligosaccharides)
• Host:
– glycosaminoglycans (GAGS) form a barrier that covers the urothelial epithelium
preventing bacterial adhesion
– Tamm-Horsfall protein: bind the fimbriae present on the bacterial surface thus
preventing them from binding to the mucous receptors and therefore favoring the
elimination of bacteria with urination
– Secretory immunoglobulins, mostly IgA but also IgG and IgM

Epidemiology
• UTIs occur in 1% to 2% of infants, about 5% of girls, and 0.5% or less of boys.
• Renal damage is related to vesicoureteral reflux, which occurs in 30% to 50% of preschool
children with infection; structural or functional obstruction also causes damage.
• UTIs are more often asymptomatic in women than men.
• Up to 60% of women have symptomatic UTIs during their lifespan, and 10% of women have
UTIs each year.
• Renal infection rarely causes end-stage renal disease without other underlying disease. Usually
these are mild infections, rarely causing any renal disease.

Risk factors
Predisposing factors in women:
• Small urethra
• Sexual activity (microtrauma to the urethral meatus)
• Pregnancy, childbirth, abortions
• Alterations of bacterial flora due to the use of antibiotics
• Age (post-menopause, due to the change of the endocrinological equilibrium)

Predisposing factors in men:

• Prostatic hyperplasia

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Predisposing factors in both:

• Instrumental investigations
• Urolithiasis
• Anatomical / functional anomalies that do not allow effective emptying of the bladder
• General disorders (eg Diabetes mellitus, immunocompromised conditions)
• Vesicoureteral reflux

Etiology
In most cases, Gram negative bacteria (mainly Enterobacteria):
• E. coli = 80% of uncomplicated UTI
• Proteus – associated with stones
• Klebsiella – associated with stones
• Enterobacter
• Serratia
• Pseudomonas

Gram positive microrganism:

• Staphylococcus saprophyticus
• Enterococcus spp. à in patients who have received invasive procedures on both genitourinary
tract or gastrointestinal tract. Bacteremia and endocarditis may be also related
• Staphylococcus aureus à similar to enterococcus, but in this case, we mainly have to think
about the hematological way and search for the pathogen on the valves by ultrasonography
imaging to search for endocarditis, since it is the most frequent pathogenic modality of infection
by S. Aureus è so when we encounter S. Aureus in a UTI, the first thing is to exclude the
presence of endocarditis!

Symptoms
Lower urinary tract infection
• Dysuria
• Pollakiuria
• Hematuria
• Cloudy urine
• Nocturia
• Suprapubic pain
• Stranguria
• Urinary urgency

When we have a complicated course of the disease, with an ascending infection up to the renal
parenchyma, or when we have a UTI but with a high load in immunocompromised patients, we may
have systemic symptoms. In this case, we have to exclude pyelonephritis by imaging. However, we have
to keep in mind that systemic symptoms may also appear in immunocompromised patients, for this
reason the recent guidelines have put these patients among the Complicated UTIs. In fact, in the
previous guidelines, complicated UTIs were just those with pyelonephritis or with alterations of the LUT
(stones, neoplasia, anatomic and congenital alterations).

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Men are also included in the complicated UTIs (ndr: not sure what she exactly meant) because we have
to consider the possibility of the presence of underlining conditions, like prostate hyperplasia or some
unrecognized conditions favoring the process of infection.
Also, pregnant women are included in the complicated UTIs, because in this group of patients we need a
different approach in case of asymptomatic bacilluria.

Acute pyelonephritis
• Fever with chills
• Malaise
• Nausea, vomiting
• Abdominal pain (lower back pain à also present in case of perirenal abscess)
• Hypotension

Peri-renal abscess
• Intermittent fever with chills (due to the intermittent release of bacteria in the blood)
• Lower back pain
• Weight loss
• Night sweats

Diagnosis
• History
• Physical examination
• Blood test (CRP, VES)
• Urinary sediment examination à for an etiological disgnosis
• Urine culture with antibiogram for targeted antibiotic therapy
• Instrumental tests: ultrasound, CT, urography, renal biopsy à to also exclude complications

CYSTITIS
• Often associated with urethritis
• Generally bacterial etiology, from intestinal bacterial flora
• E. coli: 70-95% of cases à most frequent cause

Symptoms
• Dysuria, stranguria, pollakiuria, suprapubic pain or tension
• Systemic symptoms mostly absent. Sometimes we may have sudden high fever with chills
• Low grade fever
• In case of sudden high fever, suspect pyelonephritis

Diagnosis
We have to collect 2 samples of urine:
• Urinary sediment examination
• Urine culture

Urinary sediment examination

It consists in the direct examination of urine under the microscope.

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•PMN> 5-10 (pyuria) is a sign of active infection à we need to search for pyuria
•PH evaluation: usually alkaline. In case of pyuria associated with acid pH and increase in
leukocytes, suspect tuberculosis. This is very rare and so we need a very high suspicion for this
condition
• Erythrocytes have low significance
• Leukocyte cylinders, could be associated with pyelonephritis
• Proteinuria is frequently found in UTIs (due to the ongoing inflammation process). Anytime we
have this condition, at the end, so when we no longer have symptoms, we need to reassess the
fluid status
è Nowadays, this type of test has been replaced by dipstick examination.

à Urine dipsticks for pyuria and bacteriuria are useful screening tests. They are very easy to perform
and more useful than traditional urinary examination.
à The dipstick leukocyte esterase test is a rapid screening test for detecting pyuria and has largely
replaced microscopic methods. So, we have to look for the leukocyte esterase, but also for production of
nitrates.
à A negative leukocyte esterase test plus a negative nitrite test result are strongly predictive of the
absence of UTI. So, we have to search for other causes of urinary symptoms.

Urinary culture
This is regarding the amount of bacteria.
• Significant bacteriuria: > 100,000 CFU / ml
• One culture with 103/mL or more of a gram-negative bacillary uropathogen is diagnostic
in symptomatic UTI.
• Asymptomatic Bacteriuria: Significant bacteriuria: (> 100,000 CFU / ml) without symptoms. To
confirm the presence of asymptomatic bacteriuria, we need at least 2 urinary cultures obtained
with some delay between one another (some days) and positive for the same pathogen:
• Two urine cultures with greater than or equal to 105 of the same uropathogen/mL are
required for diagnosis of asymptomatic bacteriuria.
• One third of young women with cystitis have fewer than 105 bacteria/mL urine.

This is how we define the groups of patients in order to organize our approach for diagnostic testing (in
terms of imaging) and also for treatment:
- Usually, in patients with acute simple cystitis (no risk factors, local symptoms with
no systemic symptoms) at their first episode, we may try with a conservative
approach (water intake and follow-up). In a patient with relapsing symptoms, we
may decide to perform blood tests and urine culture and to approach them with an
empirical therapy. And finally, if we have many relapses, we need to perform an
antibiogram so to administer antibiotics according to the latter.
- In acute complicated UTI, we have systemic symptoms and the presence of risk
factors (immunocompromised conditions, male sex, local alteration of local urinary
tract due to stones or other conditions), so we need to do culture and antibiogram:
• If the patient is stable, we can wait for the antibiogram’s results to
administer the proper antibiotic
• If the patient is not stable (for instance having hypotension, tachycardia,
etc.), we may immediately start empirical therapy and then adjust it
according to the microbiological results

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- There are special populations: pregnant women and renal transplant recipients.
This in fact are cases in which we have to consider treatment also upon
asymptomatic bacteriuria.

Imaging
For acute complicated UTIs, we must exclude conditions such as pyelonephritis, renal abscess or
obstruction. To do this, we need imaging.
We may start with US (without contrast medium), just to search for dilations at the level of the urinary
tract (presence of stones, obstruction, etc.).
US is not only important to confirm diagnosis of a complicated UTI, but it is also fundamental to know
how to manage these patients: in fact, rather than an antibiotic treatment, these cases require the
intervention of an urologist (to put a drainage, a stent à to resolve the obstruction).
Instead, if we want to know if we have an infectious process at the parenchymal level, we need contrast
medium with both US and CT. So, according to the guidelines, if we want to exclude renal complications,
contrast medium is required. However, using the contrast medium may be problematic for two main
reasons:
1. Because of nephrotoxicity: most patients are old with a compromised renal function, sometimes
worsened by the ongoing infection
2. Because it is frequent to have a clinic picture characterized by fever and chills, so it is impossible
to perform imaging with CM on all these patients coming to the emergency department.

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Therapy
The same 2 groups can be approached differently not only in terms of imaging, but also therapeutically.
- Remember, for recurrence of simple cystitis, perform urinary culture and wait for
positivization (2-3 days)
- For acute complicated UTI, we have 2 main classes: quinolones and beta-lactams.
• Quinolones are very effective in this kind of infections; however, there are
two problems 1) resistance to quinolones is very frequent, not only at the
hospital level but also in the community 2) they are among the most
important class for antibiotic resistance selection à so we try to spare them
for both resistance and to avoid further resistance emergencies.
• Beta-lactams are very effective.
è Usually these patients are hospitalized and we start with beta-lactam.
When the patient is stable, we may plan a follow-up therapy at an
outpatient level. Specifically, if the patient is susceptible to quinolones, we
may plan to administer them as the remaining therapy.

Usually, the treatment duration is 5-7 days for uncomplicated episodes. Between 7-14 days for
complicated episodes.
When we have an imaging highlighting pyelonephritis, we prefer to maintain a longer treatment.
In case of renal abscess, we have two ways:
§ Surgical option à with surgical drainage we have a high chance to eradicate the infection + we
reduce the antibiotic exposure
§ Otherwise, we have to complete at least 6 weeks of therapy. Here, we opt for ciprofloxacin of
Bactrim, since among all the agents they have the highest bioavailability.

ASYMPTOMATIC BACTERIURIA

There is rarely a reason for determining presence of / treating asymptomatic bacteriuria.

Except in:
- pregnancy à 20-40% of women with asymptomatic bacteriuria develops pyelonephritis during
pregnancy. Moreover, it can be associated with pre-term delivery
- in those undergoing invasive genitourinary tract procedures
- in those who have had renal transplantation, it is uncommonly followed by symptomatic
infection and is of little consequence. However, it can be associated with a worse graft function.
These are the only 3 cases in which we must search for asymptomatic bacteriuria and treat it! In all
other cases, we do not need to look for it or treat it.

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Sometimes, we may find urinary cultures positive for candida (we talk about candiduria). Asymptomatic
candiduria is encountered mainly in hospitalized patients. The general recommendations are not to
treat these episodes unless we have 1) immunocompromised patients, 2) low birth weight infants, or 3)
patients who need urologic manipulation.

CATHETER- ASSOCIATED UTI (CA-UTI)

This is another group belonging to urinary tract infections.

Pathogenesis
v Catheters may favor the onset of an infection because of foreign bodies à Inoculation of
fecal/skin bacteria into the bladder at the time of catheterization
v Extraluminal ascension (70%)
v Intraluminal contamination due to violation of the closed system (30%)

Biofilm
(From Google: Biofilms are surface-attached, structured microbial communities containing sessile cells
(bacteria and/or fungi) embedded in a self-produced extracellular matrix composed of polysaccharides,
DNA, and other components. In comparison to planktonic cells (cells in suspension), sessile cells are often
much more resistant to antimicrobial agents and this increased resistance has a considerable impact on
the treatment of biofilm-related infections)
v Initially monomicrobial, then polymicrobial
v Bacteria in the sessile phase, protected by the penetration of antibiotics and by the immune
defenses, exchange resistance mechanisms
v Some MOs such as Proteus mirabilis and Providencia stuartii produce encrustations (hydrolyze
urease creating an alkaline environment that favors mineral precipitation)

Definition and diagnosis

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Symptoms and signs New or worsening fever; altered mental status,

A III malaise, lethargy; flank pain, hematuria; pelvis
discomfort.
In patients in which the catheter was removed in the
previous 48 h, dysuria, urgency and suprapubic pain
Microbiology Isolation of ≥ 103 cfu / ml of ≥ 1 bacteria from the
A III urine sample obtained from the catheter or from
patients in which this was removed in the previous
48 h

Since patients with CA-UTI show very aspecific symptoms, we have to first rule out all the other
potential sources of infection. Only at the end, when we have ruled out all the rest, we may think about
a diagnosis of CA-UTI.
Microbiology is also of little help because it is frequent to have asymptomatic bacteriuria in patients
with urinary catheter, and interpretation is very difficult.

Indeed:
• Most hospital-acquired UTIs are associated with catheterization, and most occur in patients
without signs or symptoms referable to the urinary tract.
• CA-UTI is the most frequent health care–associated infection worldwide, accounting for up to
40% of hospital-acquired infections in US hospitals each year
• Almost all LTCFs residents with long-term indwelling catheters are bacteriuric
• Approximately 15% of cases of nosocomial bacteremia are attributable to the urinary tract, and
bacteriuria is the most common source of gram-negative bacteremia among hospitalized
patients
• However, bacteremia complicates CA-bacteriuria in only <1% to 4% of cases à so, CA-
bacteriuria is very frequent but rarely associated with invasive processes, and the mortality is
low.
• The effect of CA-bacteriuria on mortality remains controversial
• CA-bacteriuria results in considerable antimicrobial use (often inappropriate) in hospitals and
LTCFs and comprises a large reservoir of antimicrobial-resistant organisms that contribute to
the problem of cross-infection.
• The most effective way to reduce the risk of CA-bacteriuria is to avoid unnecessary
catheterization and to remove the catheter promptly when it is no longer needed.

When we suspect an infection due to a urinary catheter that has been there for more than 2 weeks à
replace it (before urinary culture, otherwise we detect the bacteria contaminating the catheter).
• If an indwelling catheter has been in place for >2 weeks at the onset of CA-UTI and is still
indicated, the catheter should be replaced to hasten resolution of symptoms and to reduce the
risk of subsequent CA-bacteriuria and CA-UTI (A-I)
• The urine culture should be obtained from the freshly placed catheter prior to the initiation of
antimicrobial therapy to help guide treatment (A-II).

How the sample should be collected:

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v Short-term catheter: from the tap

v Long-term catheter (> 2 weeks): change catheter and take sample from tap before starting
antibiotic therapy
è Send the sample as soon as possible to avoid bacterial overgrowth.

Regarding the choice of empirical therapy, we have to consider risk factors since these episodes are
hospital-acquired or healthcare-associated à mainly for MDR etiology, especially if another gram
negative MDR has been isolated in the past month.

Intra-Abdominal Infections
v IAI second most common source of severe sepsis
v Mortality is approximately 25% to 35%, but may exceed 70%
v Common cause of readmission

Classification
We can classify intra-abdominal infections into:
v Infections limited to the bowel
v Peritonitis
• Primary (spontaneous peritonitis, for instance in patients with peritoneal dialysis.
However, in the latter case, we can also have non-spontaneous peritonitis because of
foreign bodies favoring the entry and proliferation of bacteria)
• Secondary (due to an infection process that has passed the bowel barrier. Secondary are
usually post-operative peritonitis)
• Tertiary (due to an infection process that has passed the bowel barrier. Tertiary are
usually when we have a chronicized process at the level of the peritoneum à very
complex cases with several events of secondary peritonitis which eventually develop
into a tertiary one)
v Intra-abdominal abscesses à localized disease at the level of the peritoneum without
inflammatory reaction

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Another distinction can be:

v Uncomplicated IAI: involves intramural inflammation of the GI tract
v Complicated IAI: extends beyond the hollow viscus of origin into the peritoneal space and is
associated with either abscess formation and peritonitis

UNCOMPLICATED IAI – ACUTE DIARRHEA

Uncomplicated IAI: the most important infection we have in this class is gastro-intestinal infection that
manifest as Acute Diarrhea.

Definition
Diarrhea is defined as the passage of loose or watery stools, typically at least three times in a 24-hour
period.

Type of Diarrhea
• Acute – 14 days or fewer in duration
• Persistent diarrhea – more than 14 but fewer than 30 days in duration
• Chronic – more than 30 days in duration

Invasive diarrhea/dysentery: diarrhea with visible blood or mucus, commonly associated with fever and
abdominal pain.

Etiology
- Viruses (norovirus, rotavirus, adenoviruses, astrovirus, and others)
- Rotavirus is important in children and in immunocompromised pts.
- Adenoviruses may have a complicated course of disease usually associated with
encephalitis and with parainfections
- Bacteria (Salmonella, Campylobacter, Shigella, enterotoxigenic Escherichia
coli, Clostridioides [formerly Clostridium] difficile, and others)
- Salmonella, Campylobacter and Shigella are the most important and common causing
diarrhea
- E. Coli is instead more frequent in patients returning back from travels
- Protozoa (Cryptosporidium, Giardia, Cyclospora, Entamoeba, and others)
- Cryptosporidium is a common cause in immunocompromised patients

• Most cases of acute infectious diarrhea are viral

• Severe diarrhea is often bacterial
• Protozoa are less commonly identified as the etiologic agents of acute gastrointestinal illness.

Noninfectious etiologies become more common as the course of the diarrhea persists and becomes
chronic.

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Evaluation
History
• duration of symptoms
• frequency and characteristics of the stool (ask for the presence of mucus and blood)
• associated symptoms (maybe systemic)

Potential exposures:
• Food history
• Residence in nursing home/LTCF
• Occupational exposure
• Pets and hobbies

Food history
Food history is very important to be investigated since sometimes can lead to the identification of the
pathogen.

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Diarrhea onset:
§ Within 6 hours: suggests ingestion of a
preformed toxin of Staphylococcus
aureus or Bacillus cereus, particularly if
nausea and vomiting were the initial
symptoms à so not an invasive infection
§ At 8 to 16 hours: suggests infection
with Clostridium perfringens (aerobic
bacteria that can contaminate food)
§ At more than 16 hours: suggests either
viral or other bacterial infection (e.g.,
contamination of food with
enterotoxigenic or STEC or other
pathogens)

Shiga toxin-producing E.coli is particularly

important to remember. In fact, few years ago,
there was an outbreak in Germany due to
contaminated pickles.
Shiga toxin is a toxin that causes uremic
hemolytic syndrome in children (it is a toxin-
mediated process).

Clostridium difficile is another important cause of watery diarrhea. Frequently associated with
nosocomial diarrhea or diarrhea associated with antibiotics. All of us has a little amount of C. difficile in
our bowel, however during some acute events we may have an alteration of our gut microbiota à the
amount of Clostridium may increase favoring also the increase in strains producing toxins.

Medical history
• Recent antibiotic use (C. difficile infection)
• Other medications (such as proton pump inhibitors, which can increase the risk of infectious
diarrhea)
• Immunocompromised host or the possibility of nosocomial infection)

Physical examination
• The abdominal examination should evaluate for findings that can suggest ileus or peritonitis,
including abdominal distension, pain with gentle percussion

General laboratory tests

• Laboratory tests are not routinely warranted, especially in self-limited cases
• Complete blood count does not reliably distinguish bacterial etiologies of diarrhea from others,
but may be helpful in suggesting severe disease or potential complications.

Imaging
• Abdominal imaging is not typically warranted in patients with acute diarrhea and rarely changes
the clinical management

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Stool tests for bacterial pathogens

This is important for etiological diagnosis.
For most patients who do not have severe illness or high-risk comorbidities, it is reasonable to continue
expectant management for several days without microbiologic stool testing.

Severe illness
• Profuse watery diarrhea with hypovolemia
• Passage of >6 unformed stools per 24 hours
• Severe abdominal pain
• Need for hospitalization
• Symptoms persisting for more than one week

Inflammatory diarrhea
• Bloody diarrhea
• Passage of many small volume stools containing blood and mucus
• Temperature ≥38.5ºC (101.3ºF)

High-risk host features

• Age ≥70 years
• Comorbidities which may be exacerbated by hypovolemia or rapid infusion of fluid
• Immunocompromising condition
• Inflammatory bowel disease
• Pregnancy

Stool culture
• The optimal specimen for culture is a diarrheal stool specimen inoculated onto culture plates as
quickly as possible.
• A routine stool culture will identify Salmonella, Campylobacter, and Shigella. If the patient has
been hospitalized for > 3 days, it is suggested to also look for C. difficile.
• E. coli O157:H7- (Shiga toxin producing) can be isolated on sorbitol-MacConkey plates or
identified with antigen testing or polymerase chain reaction of stool. We have to remember that
we should be careful at administering antibiotics to these patients, since we may have an
increase in shiga toxin release and onset of uremic hemolytic syndrome, as previously said.

Multipathogen molecular panels

• Molecular tests for a panel of bacterial, viral and parasitic pathogens performed simultaneously
on diarrheal stool samples and, in some cases, rectal swabs.
• Listeria infections has to be kept in mind since it may be particularly common in
pregnant women and immunocompromised patients. Listeria gastroenteritis can be
complicated by CNS infection, as one of the causes of acute bacterial meningitis.
Sometimes, this kind of meningitis presents with more subtle symptoms than acute
bacterial meningitis. When we perform lumbar puncture, the liquor is pleiotropic, not
many PMNs, glucose may be reduced but not as much as in case of other bacterial
pathogens, proteins are increased. Again, all this is typical of immuncompromised
patients and those with several comorbidities.
Sometimes, we also have endocardial locations, so endocarditis, from Listeria.
In pregnant women, we may have a very important complication of listeria: placentitis,

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with severe sepsis. So, when a pregnant woman presents with gastroinstestinal
symptoms, we have to ask for food history (may be due to pre-cooked food), and search
for Listeria in both stool and blood. Moreover, we should strictly monitor the placenta
• Some evidence suggests that stool multiplex polymerase chain reaction (PCR) tests can decrease
health care utilization costs and antibiotic prescribing

Specific situations

Bloody diarrhea
• STEC: direct testing on stools (with immunoassays or molecular tests) for Shiga toxin
• Entamoeba
Persistent diarrhea
• parasitic organisms and other evaluation for non-infectious processes (Giardia, Cryptosporidium,
and E. histolytica) à can be diagnosed by microscopy for ova and parasites. 3 specimens should
be sent on consecutive days for ova and parasite examination. Laboratory should be alerted to
the potential diagnosis, and specific stains for the organisms should be requested.
Antibiotic or health care exposures
• C. difficile
Immunocompromised patients
• CMV à most of us are seropositive since we acquire this virus as infants. It remains latent
during our life, but it can reactivate in immunocompromised, producing systemic or local
symptoms. Some groups are at higher risk of CMV-gastrointestinal disease, such as those with
inflammatory bowel disease and with solid organ transplants.

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Management

General measures
Fluid repletion
• The most critical therapy in diarrheal illness is rehydration, preferably by the oral route, with
solutions that contain water, salt, and sugar
• Severe hypovolemia should initially receive intravenous fluid repletion. Once they are repleted,
they can be switched to oral rehydration solutions.
Dietary recommendations
• Adequate nutrition during an episode of acute diarrhea is important to facilitate enterocyte
renewal

Antibiotic therapy
Antibiotic therapy is not indicated in most cases since the illness is usually self-limited.

Empiric antibiotic therapy

• We do not routinely use empiric antibiotics in adults with acute diarrhea, which is usually short-
lived and caused by viruses.
• The benefit from antibiotic use does not outweigh the drawbacks of potential side effects,
promotion of bacterial resistance, eradication of normal flora (and increased risk of C.
difficile infection), and cost.

Specifically, we often use empiric antibiotics in the following circumstances:

• Severe disease (fever, more than six stools per day, volume depletion warranting
hospitalization)
• Suspicion of invasive bacterial infection (bloody or mucoid stools)
• Host factors that increase the risk for complications (age >70 years old and comorbidities such
as cardiac disease and immunocompromising conditions)

Empiric antibiotic therapy:

Azithromycin: Single 1 g dose (for patients without dysentery) or as 500 mg once daily for three days. It
is associated with lower complications in case of E. coli shiga toxin-producing infection.

Fluoroquinolone:
Fluoroquinolones are very effective, but we have to remember that in some parts of the world we have
a high resistance against them, in particular in south-east Asia.
- Ciprofloxacin (a single 750 mg dose or 500 mg twice daily for three to five days)
- Levofloxacin (500 mg as a single dose or given once daily for three to five days).

Azithromycin is preferred for patients with fever or dysentery (bloody or mucoid diarrhea) and in
patients at risk for a fluoroquinolone-resistant pathogen (diarrhea after travel to Southeast Asia, or
during outbreaks of resistant pathogens).

Specific antibiotic therapy

• Shiga toxin-producing E. coli (STEC) specifically should not be treated with antibiotics

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Symptomatic therapy
Antimotility agent (loperamide): should be used cautiously in patients in whom fever is absent or low
grade and the stools are not bloody.

Probiotics: Probiotics with beneficial bacteria that assist in maintaining or recolonizing the intestine with
non-pathogenic flora can also be used as alternative therapy.

COMPLICATED IAI
Classification
v Community acquired IAI
v Health-care associated IAI
ü Presence of invasive device at time of admission
ü History of MDR infection or colonization
ü History of surgery, hospitalization, dialysis, or residence in a long-term care facility in the
last 12 month
ü Hospital onset of IAI (> 48 h)

Severity stratification

Epidemiology

CIAO study àthis is one of the largest studies about complicated IAI
v From 66 European hospitals, Jan-March 2012
v 912 pts with complicated IAIs, mean age was 54.4 years
v It was found that: 83.3% were CA-IAI (community-acquired), 16.7% were HCA-IAI (healthcare-
associated)

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Etiology
Here we can visually see the most common pathogens responsible for complicate-IAI.

The type of flora we find in case of complicated-IAI depends on the

tract affected. Usually, we find more anaerobic gram positive in the
upper tract, in the lower tract we have the alteration in
enterebacteric bacilli. At the level of small bowel and stomach we
may also have yeasts.

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In the graph, infection source and etiology:

Notice that yeasts are more common in case of gastroduodenal perforation, this is important because
usually, when we have post-operative peritonitis, we start with antibiotic terapy, but instaed we my
start with antifungal therapy in patients with gastroduedanl perforation or with risk factors for fungal
diasease that include high clinical severity, long-antibiotic exposure, long-history of parenteral nutrition.

Diagnostic testing
Tests
v BCs (blood cultures)
v Surgical sample (at least 1 mL)
- Gram stain (CIII)
- Cultures for aerobic and anaerobic bacteria (AI)

If the sample is sent after 24-48h, it loses significance.

è we should try to obtain the sample either during surgery or after the position of the
drainage.

Management
The management doesn’t just consist in antibiotic therapy. Antibiotic therapy is adjuvat to the favorable
course of the patient, but the management should be shared among surgeons, pharmacologists,
radiologists, intensivists.
The patient may sometimes start with a renal replacement therapy.

Antimicrobial therapy
- On one side, we need to provide an early adequte antibiotic therapy because it imporves the
outcome.
- On the other side, we have to avoid overuse to avoid furthur resistance. Fo example,
enterobacteria are very prone to acquire resistance.
- We have to administer an empirical therapy tailored on risk factors, clinical severity,
epidemiological evaluation, presumed source, previous colonization, immunocompromised
condition.
- Right dose, right schedule, de-escalation, avoid prolonged duration
- For all complicated-IAI, the therapy is IV antibiotics, usually large-sectrum antibiotics in hospital

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Lecture 04 Infectious Diseases 20/10/2021

- In patients with cholecystitis, the use of antibiotics is controversial since the clinical picture can
be kept under controll with a good surgical prophylaxis.
- For C. Difficile infection, the standard therapy is oral vancomycin (which is completely different
from iv vancomycin). Dosage: 125mg, 4 times a day, for 10 days.

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