*2.2.1. Generalised septicaemic infections*

The generalised septicaemic infection is an infection with an unpredictable outcome, high severity and increased mortality in the absence of adequate treatment. The correct choice of empirical antibiotic treatment depends on the intelligent use of clinical knowledge and epidemiological and microbiological data regarding the pathology in the area where the patient comes from. The lack of knowledge on the local resistance prevalence is a predictive factor for an incorrect treatment. The basic principle, which guides the treatment of the critical patient, is to rapidly initiate antibiotic treatment at correct doses, concordant with the pharmacokinetic and pharmacodynamic characters of the chosen drug and to adapt the treatment to the changes occurring in the clinical evolution and to the results of the antimicrobial sensitivity tests as soon as these become available.

Immediately after a patient with suspected sepsis is admitted, an attentive anamnesis and a thorough clinical examination are conducted in order to establish the entry and the location of the primary and secondary septic sites. The first emergency microbiological investigations are conducted (repeated blood cultures, cultures from secretions, lesions, urine, sputum, exudates, pleural fluid, etc.) together with evaluations of the renal, hepatic functions and state of consciousness, thus determining the severity of the case [8, 9].

The practical approach includes the emergency admission of the patient into the ICU where prevention or correction of hypovolemia, functional and metabolic dysfunctions are attempted, concomitantly with the prompt initiation of antibiotic treatment according to the maximal probability criterion.

The correct antibiotic treatment targets the resident microbial flora in the organ presumed to be the source of the infectious process.

The empirical treatment of sepsis consists of the association of bactericidal antibiotics with synergistic actions or monotherapy with an ultra-broad-spectrum antibiotic; antibiotics are administered intravenously in order to rapidly achieve an effective concentration in the infection site.

Empirical antibiotic therapy proved to be equally effective in beta-lactam-aminoglycoside associations, monotherapy with carbapenems, broad-spectrum penicillins/beta-lactamase inhibitors (ticarcillin/clavulanic acid, piperacillin/tazobactam) or third- and fourth-generation cephalosporins [10].

The aetiology of sepsis varies with the age of the patient, and the empirical treatment must be adapted to the most probable aetiology, but correlated with age, weight and associated pathology.

Adults with severe sepsis of unknown source must be treated with antibiotics effective against Gram-negative bacilli, *Staphylococcus aureus*, streptococci, respectively carbapenems (meropenem or imipenem) plus vancomycin. Septic shock requires the urgent refilling of the vascular system by infusions with saline solutions until the central venous pressure is re-established (over 80 mm at 6 h from hospital admission); at the same time, the primary source of infection is investigated, blood culture is collected and the first dose of antibiotic is administered, knowing that the time from admission to the initiation of antibiotic therapy is the strongest prognostic factor.

catheters used for the haemodynamic monitoring and peripheral catheters show lower infec-

Infections and Multidrug-Resistant Pathogens in ICU Patients

http://dx.doi.org/10.5772/intechopen.79229

21

The removal of intra-vascular, gastric or bladder catheters, neurosurgical shunts, etc. as soon as they are no longer needed, represents an infection prevention measure. Both their insertion and removal is done by specialised staff, trained to work under sterile conditions, avoiding the risk of contamination. Knowing that invasive devices, catheters included, are the most frequent cause of HCAIs, their insertion must be conducted under aseptic conditions, choosing the most suitable site (for instance, sub-clavian rather than femoral), after ensuring the asepsis of the cutaneous area, preferably with chlorhexidine, and not with alcohol or iodine solutions. In severely immunocompromised patients, the recommendation is to use antibiotic-impregnated catheters. Clinical studies confirm the significant reduction in catheter-associated infec-

An increasing number of patients require central venous catheters for long periods of time (for haemodialysis, total parenteral nutrition, chemotherapy), which favours complications such as thrombosis or infection. Central venous catheter-associated bacteraemia imposes the removal of the catheter and systemic administration of antibiotics. The clinical decision to remove a catheter suspected of infection relies on the presence of local infection signs. The decision to maintain the device is made in the absence of severity signs in patients with tech-

There are situations when catheters may not be removed or replaced (lack of venous approach, counter indication of a new intervention, etc.). In such cases, attempts are made to save the venous line by eliminating the intra-luminal colonisation before the onset of bacteraemia or, once bacteraemia is present, the general administration of antibiotic is associated with exposing the inner surface of the catheter, after its closure, at a very high concentration of the adequate antibiotic meant to eradicate the colonisation. This technique proved effective in the case of Gram-negative bacilli and coagulase-negative staphylococci, but it is not recom-

UTIs are the most frequent HCAIs. In most hospitals, catheter-related bacteriuria represents 40% of all HCAI within 1 year. The decision to treat is made after discriminating between the presence of bacteria (colonisation) and symptomatic infectious processes. The signs of

tions when these are removed as soon as their role is no longer essential [15–17].

tion risks than central venous caterers (**Table 2**).

nical difficulties of catheter reinsertion in a new site.

mended in colonisations with *S. aureus* [18].

**Table 2.** Distribution of the infection risk in the intra-vascular catheterisation.

**2.3. Urinary tract infections**

Patients admitted in a state of septic or toxic-septic shock will not be treated with betalactam (The bacterial load is very high, the pathogens are in a stationary phase with low protein synthesis, hence with a low synthesis of penicillin-binding proteins, so antibiotics lack their target.)

Colistin has a rapid antibacterial effect completed by a significant post-antibiotic effect against *P. aeruginosa*, *A. baumannii* and *K. pneumoniae*. The most effective administration regimen is at 8 h. Colistin proved an important alternative in the treatment of MDR Gram-negative bacilli. Resistance to colistin is caused by sub-optimal doses. Colistin dosage must be optimised, as this antibiotic is the last option in the treatment of MDRO [11–13].

When a biliary infection is suspected to be at the origin of bacteraemia, the most frequently encountered bacteria are enterococci and aerobic Gram-negative bacilli, which respond well to piperacillin/tazobactam or ticarcillin/clavulanate; alternatively, ceftriaxone, ciprofloxacin or levofloxacin associated to metronidazole may be administered.

A great part (around 25%) of sepsis cases occur as a result of community or hospital-acquired urinary tract infections (UTI), evolving with a renal or complication of prostatic parenchyma. In such cases, the time from hospital admission to the initiation of antibiotic treatment is also decisive for the evolution. After collection of samples for blood and urine cultures, the first dose of broad-spectrum antibiotic active against *E.coli*, *Proteus* spp., *Enterobacter* spp., *Klebsiella* spp., *P. aeruginosa* is administered; more rare cases of sepsis of urinary origin may be caused by Gram-positive bacteria (15%) or by *Pseudomonas* spp., especially in patients with immune deficits. For an effective treatment of community-acquired urosepsis, depending on the type of local susceptibility, a third-generation cephalosporin or a fluoroquinolone may be indicated; in urosepsis following urologic surgery in patients with long-term urinary catheters, the association of a third-generation cephalosporin active against *Pseudomonas* or piperacillin/tazobactam with an aminoglycoside or a carbapenem is useful, this association being required to cover MDRO [14].

It should be noted that treatment in sepsis is complex, antibiotic therapy being accompanied with measures to eradicate the entry site and septic metastases, to correct tissue hypoxia and to maintain hydro-electrolyte and acid-base balance.

#### *2.2.2. Infections associated with invasive devices*

Invasive devices (endotracheal, intra-vascular catheters) increase the risk of HCAI especially with MDRO, by colonisation and biofilm formation on the internal surface of these devices. All types of intra-vascular devices may become complicated with blood infections, but arterial catheters used for the haemodynamic monitoring and peripheral catheters show lower infection risks than central venous caterers (**Table 2**).

The removal of intra-vascular, gastric or bladder catheters, neurosurgical shunts, etc. as soon as they are no longer needed, represents an infection prevention measure. Both their insertion and removal is done by specialised staff, trained to work under sterile conditions, avoiding the risk of contamination. Knowing that invasive devices, catheters included, are the most frequent cause of HCAIs, their insertion must be conducted under aseptic conditions, choosing the most suitable site (for instance, sub-clavian rather than femoral), after ensuring the asepsis of the cutaneous area, preferably with chlorhexidine, and not with alcohol or iodine solutions. In severely immunocompromised patients, the recommendation is to use antibiotic-impregnated catheters. Clinical studies confirm the significant reduction in catheter-associated infections when these are removed as soon as their role is no longer essential [15–17].

An increasing number of patients require central venous catheters for long periods of time (for haemodialysis, total parenteral nutrition, chemotherapy), which favours complications such as thrombosis or infection. Central venous catheter-associated bacteraemia imposes the removal of the catheter and systemic administration of antibiotics. The clinical decision to remove a catheter suspected of infection relies on the presence of local infection signs. The decision to maintain the device is made in the absence of severity signs in patients with technical difficulties of catheter reinsertion in a new site.

There are situations when catheters may not be removed or replaced (lack of venous approach, counter indication of a new intervention, etc.). In such cases, attempts are made to save the venous line by eliminating the intra-luminal colonisation before the onset of bacteraemia or, once bacteraemia is present, the general administration of antibiotic is associated with exposing the inner surface of the catheter, after its closure, at a very high concentration of the adequate antibiotic meant to eradicate the colonisation. This technique proved effective in the case of Gram-negative bacilli and coagulase-negative staphylococci, but it is not recommended in colonisations with *S. aureus* [18].

#### **2.3. Urinary tract infections**

Adults with severe sepsis of unknown source must be treated with antibiotics effective against Gram-negative bacilli, *Staphylococcus aureus*, streptococci, respectively carbapenems (meropenem or imipenem) plus vancomycin. Septic shock requires the urgent refilling of the vascular system by infusions with saline solutions until the central venous pressure is re-established (over 80 mm at 6 h from hospital admission); at the same time, the primary source of infection is investigated, blood culture is collected and the first dose of antibiotic is administered, knowing that the time from admission to the initiation of antibiotic therapy is

Patients admitted in a state of septic or toxic-septic shock will not be treated with betalactam (The bacterial load is very high, the pathogens are in a stationary phase with low protein synthesis, hence with a low synthesis of penicillin-binding proteins, so antibiotics

Colistin has a rapid antibacterial effect completed by a significant post-antibiotic effect against *P. aeruginosa*, *A. baumannii* and *K. pneumoniae*. The most effective administration regimen is at 8 h. Colistin proved an important alternative in the treatment of MDR Gram-negative bacilli. Resistance to colistin is caused by sub-optimal doses. Colistin dosage must be optimised, as

When a biliary infection is suspected to be at the origin of bacteraemia, the most frequently encountered bacteria are enterococci and aerobic Gram-negative bacilli, which respond well to piperacillin/tazobactam or ticarcillin/clavulanate; alternatively, ceftriaxone, ciprofloxacin

A great part (around 25%) of sepsis cases occur as a result of community or hospital-acquired urinary tract infections (UTI), evolving with a renal or complication of prostatic parenchyma. In such cases, the time from hospital admission to the initiation of antibiotic treatment is also decisive for the evolution. After collection of samples for blood and urine cultures, the first dose of broad-spectrum antibiotic active against *E.coli*, *Proteus* spp., *Enterobacter* spp., *Klebsiella* spp., *P. aeruginosa* is administered; more rare cases of sepsis of urinary origin may be caused by Gram-positive bacteria (15%) or by *Pseudomonas* spp., especially in patients with immune deficits. For an effective treatment of community-acquired urosepsis, depending on the type of local susceptibility, a third-generation cephalosporin or a fluoroquinolone may be indicated; in urosepsis following urologic surgery in patients with long-term urinary catheters, the association of a third-generation cephalosporin active against *Pseudomonas* or piperacillin/tazobactam with an aminoglycoside or a carbapenem is useful, this association

It should be noted that treatment in sepsis is complex, antibiotic therapy being accompanied with measures to eradicate the entry site and septic metastases, to correct tissue hypoxia and

Invasive devices (endotracheal, intra-vascular catheters) increase the risk of HCAI especially with MDRO, by colonisation and biofilm formation on the internal surface of these devices. All types of intra-vascular devices may become complicated with blood infections, but arterial

this antibiotic is the last option in the treatment of MDRO [11–13].

or levofloxacin associated to metronidazole may be administered.

the strongest prognostic factor.

20 Current Topics in Intensive Care Medicine

being required to cover MDRO [14].

to maintain hydro-electrolyte and acid-base balance.

*2.2.2. Infections associated with invasive devices*

lack their target.)

UTIs are the most frequent HCAIs. In most hospitals, catheter-related bacteriuria represents 40% of all HCAI within 1 year. The decision to treat is made after discriminating between the presence of bacteria (colonisation) and symptomatic infectious processes. The signs of


**Table 2.** Distribution of the infection risk in the intra-vascular catheterisation.

catheter-associated UTIs are fever, lateral lumbar pain, sensitivity in the costovertebral angle, haematuria and delirium with recent onset. After catheter removal, pollakiuria or dysuria may be present.

Most hospital-acquired UTIS are expensive and may be prevented. The implementation of protocols based on present guidelines will reduce the inadequate use, as well as the antimicrobial resistance. When catheterisation is necessary, its duration should be limited. In case infections occur, the empirical treatment should be conducted according to the suspected pathogens and on the hospital's antibiogram. When the results of cultures become available, antibiotics narrow their spectrum. The treatment should be limited to 7–14 days, depending on the response to treatment. Catheter removal is a key factor because catheterisation increases the risk for hospital-acquired UTI and other complications, resulting in prolonged

Infections and Multidrug-Resistant Pathogens in ICU Patients

http://dx.doi.org/10.5772/intechopen.79229

23

Intra-abdominal infections include a series of diseases with variable severity, from uncomplicated appendicitis to faecal peritonitis. Uncomplicated infections involve a single organ and may not reach the peritoneum, and they may be solved either by surgical resection or by administration of antibiotics. Complicated intra-abdominal infections are those which extend to the peritoneum causing localised or generalised peritonitis; in order to solve these, the

The antimicrobial therapy of intra-abdominal infections, which are to be solved percutaneously or by surgery, has the following goals: to accelerate the elimination of the infecting microorganisms, to decrease the recurrence risk of the intra-abdominal infection, to shorten the clinical evolution, to limit the expansion of the infection to the abdominal wall and to

The antibiotic therapy is initiated after hydroelectrolyte rebalance, the restored volemia determining the restoration of the visceral perfusion and a better distribution of the medication. Moreover, this diminishes the side effects of antibiotics, which have been exacerbated by the

The empirical antibiotic treatment is initiated in concordance with the most probable microbiological spectrum, the type and density of germs being dependant on the level where the perforation of the digestive tract has occurred. By gastric, duodenal and proximal jejunal perforations, a low number of aerobic Gram-positive and anaerobic Gram-negative bacteria, generally sensitive to cephalosporins, are released into the peritoneum. *Candida albicans* has also been isolated, but antifungal treatment is only required in the case of patients under immunosuppressive treatment or in patients with recurrent intra-abdominal infections. The perforations of the distal small intestine often evolve as localised abscesses and peritonitis only takes place when these are ruptured. The intra-abdominal infections propagated from the colon into the peritoneum are caused by anaerobic or facultative anaerobic Gram-negative

The selection of the antibiotic should then be guided by the results of the cultures from the biological specimens obtained by percutaneous drainage or during the surgical intervention, but until these become available, it is necessary and useful to perform the microscopical examination directly on a Gram-stained smear. If high numbers of Gram-positive cocci are

infection source must be solved by both surgery and antibiotic therapy.

decrease the risk of generalisation of the infectious process.

deficitary perfusion of internal organs.

bacteria; *Bacteroides fragilis* is sometimes present.

hospitalisation and increased costs [20, 21].

**2.4. Intra-abdominal infections**

The Infectious Disease Society of America defines asymptomatic bacteriuria as the absence of symptoms with the presence of over 105 colony forming units/ml of one or more bacterial species in a catheterised patient. In most cases of asymptomatic bacteriuria, the treatment led to the temporary sterilisation of urine and not to the eradication of pathogens [19]. Additionally, in 33–50% of patients, after catheter removal, the bacteriuria spontaneously resolved. This is why treating an asymptomatic bacteriuria increases the risk of antimicrobial resistance or of adverse reactions associated with useless antibiotic treatment.

Some pathogenic bacteria produce biofilms, which consist of an adherent layer of microorganisms and their extracellular products. The biofilm protects the pathogens against the host's defence mechanisms and against antibiotic therapy. Migration to the urinary bladder occurs in 1–3 days. The duration of catheterization is an important risk factor, with almost all patients who are catheterised for more than 30 days developing bacteriuria. These patients are at risk of upper urinary tract inflammation, which increases the risk of bacteraemia. Infections linked to long-term catheterisation are often polymicrobial, which involves a broad-spectrum treatment.

The selection of antibiotics used for the treatment of catheter-associated UTIs depends on the result of the microscopical examination, as well as on the colonial characters. In 60–80% of cases, the causative agent is a Gram-negative bacillus (*E.coli*, *Klebsiella* spp., *Pseudomonas* spp., *Proteus* spp., *Enterobacter* spp.). The remaining 20–40% is caused by Gram-positive bacteria, most often species of staphylococci or enterococci. The empirical treatment has to take the following factors, which increase the risk of antibiotic resistance: the duration of hospitalisation, previous administration of antibiotics, and local resistance patterns.

Urinary fluoroquinolones (ciprofloxacin and levofloxacin) are administered to patients with mild and moderate infections, who are considered haemodynamically stable and do not present an altered mental status. Moxifloxacin is not recommended, as it does not reach effective urine concentrations. Broad-spectrum cephalosporins, ceftriaxone or cefepime, may also be used. In patients with urosepsis or in those haemodynamically unstable (hypothermia, tachycardia over 90/minute, tachypnoea over 20 respirations/minute or Pco2 under 33 mmHg, leukocytosis over 12,000/mm<sup>3</sup> or leukopenia under 4000/mm<sup>3</sup> ) piperacillin-tazobactam is administered.

In medium clinical forms, ciprofloxacin, 400 mg iv, for every 12 h or levofloxacin 500 mg iv /24 h or ceftriaxone for 1 g iv/day are administered.

The recommended treatments in severe forms include: cefepime 2g iv/12h, ceftazidime 2g iv/8h, imipenem 500 mg iv/6 h, doripenem 500 mg iv/8 h, meropenem 1 g/8 h and piperacillin/tazobactam 3.375 g iv/6 h.

The treatment of UTIs associated with bladder catheterisation is done with antibiotics for 3 days in women aged over 65 years, from whom the catheter has been removed; otherwise, the treatment is given for 7 days. The duration of levofloxacin treatment is 5 days.

Most hospital-acquired UTIS are expensive and may be prevented. The implementation of protocols based on present guidelines will reduce the inadequate use, as well as the antimicrobial resistance. When catheterisation is necessary, its duration should be limited. In case infections occur, the empirical treatment should be conducted according to the suspected pathogens and on the hospital's antibiogram. When the results of cultures become available, antibiotics narrow their spectrum. The treatment should be limited to 7–14 days, depending on the response to treatment. Catheter removal is a key factor because catheterisation increases the risk for hospital-acquired UTI and other complications, resulting in prolonged hospitalisation and increased costs [20, 21].
