**2.4. Intra-abdominal infections**

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

The Infectious Disease Society of America defines asymptomatic bacteriuria as the absence of

cies 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

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,

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,

or leukopenia under 4000/mm<sup>3</sup>

In medium clinical forms, ciprofloxacin, 400 mg iv, for every 12 h or levofloxacin 500 mg iv /24 h

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/tazo-

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.

colony forming units/ml of one or more bacterial spe-

under 33 mmHg,

) piperacillin-tazobactam is

may be present.

22 Current Topics in Intensive Care Medicine

symptoms with the presence of over 105

leukocytosis over 12,000/mm<sup>3</sup>

or ceftriaxone for 1 g iv/day are administered.

administered.

bactam 3.375 g iv/6 h.

adverse reactions associated with useless antibiotic treatment.

previous administration of antibiotics, and local resistance patterns.

tachycardia over 90/minute, tachypnoea over 20 respirations/minute or Pco2

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

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 decrease the risk of generalisation of the infectious process.

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 deficitary perfusion of internal organs.

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 bacteria; *Bacteroides fragilis* is sometimes present.

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 present, these are very likely to be enterococci or other faecal streptococci, which imposes the association of vancomycin.

cerebrospinal fluid (CSF) collection, in cases of expansive intra-cranial processes accompanied by papilledema or focal signs. In this latter situation, computerised tomography (CT) or nuclear magnetic resonance (NMR) examinations should be conducted after blood collection for blood culture and after the first dose of antibiotic, despite the risk of excessive treatment.

Infections and Multidrug-Resistant Pathogens in ICU Patients

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*The antibiotic administration route* in meningitis is intravenous, which is capable to ensure the CSF bactericidal concentrations; the exception is for rifampicin, which may be administered orally and is useful in the treatment of meningitis caused by beta-lactam-resistant pneumo-

*Antibiotic selection*: in the treatment of bacterial meningitis, bactericidal antibiotics able to cross the blood-brain barrier are administered, so that optimal CSF concentrations are ensured regardless of the meningeal inflammation degree (meningeal inflammation favours the penetration of the antibiotic in the sub-arachnoid space at the onset of the disease, but as the inflammation regresses under treatment, the concentration tends to decrease, so that higher

Patients with suspected bacterial meningitis will be initially treated with a broad-spectrum antibiotic concordant to the most probable aetiology, the selection being made depending on the age and comorbidities. After establishing the aetiology and antibiotic susceptibility of the isolated pathogen, the antibiotic therapy will be focused, maintaining the high doses and

The lumbar puncture should be repeated after the first 24–36 h from the initiation of the treat-

The immune competent adult with bacterial meningitis requires an initial antibiotic treatment aiming at meningococcus and pneumococcus, consisting in the association of ceftriaxone (2 g/12 h) or cefotaxime (2 g/6 h) with vancomycin (30–60 mg/kg/day for every 8 or 12 h); third-generation cephalosporins must be administered even if the antibiogram shows that the respective strain presents intermediate sensitivity or resistance, because vancomycin acts

Patients with bacterial meningitis and compromised cell immunity due to pre-existing conditions or immunosuppressive treatment, but with conserved renal function, should be treated with vancomycin (60 mg/kg/day divided into two or three doses) plus cefepime (6 g/day

If a *Listeria* infection is suspected, the empirical treatment may consist in the association between vancomycin and moxifloxacin (400 mg in a single daily dose) plus trimethoprim-

The duration of the antibiotic treatment in meningitis is not standardised, but it should be individualised based upon the clinical response of each patient, but usually 7 days of treatment is sufficient for meningococcal and *H. influenzae* meningitis, 10–14 days for pneumococcal meningitis, 14–21 days for meningitis with *S. agalactiae* and 21 days or more for meningitis with *L. monocytogenes*; meningitis with aerobic Gram-negative bacilli requires antibiotic

ment in order to assess CSF cytological, biochemical and bacteriological changes.

divided into three doses) or meropenem (6 g/day divided into three doses).

coccus and coagulase-negative staphylococci.

intravenous administration.

doses are required as compared to other diseases) [23].

synergically and increases the efficiency of the therapy [24].

sulfamethoxazole (10–20 mg/kg/day divided at 6 or 12 h).

administration for 21 or 14 days after the last CSF sterile culture.

Aerobic and anaerobic Gram-negative cocci may be covered by administration of cefoxitin, ampicillin/sulbactam, piperacillin/tazobactam, imipenem, meropenem, moxifloxacin, while aerobic Gram-negative bacilli may be destroyed with aminoglycosides, second-, third- and fourth-generation cephalosporins, aztreonam, antipseudomonal penicillins or fluoroquinolones (ciprofloxacin, levofloxacin). It must be mentioned that ertapenem is not active on *Pseudomonas aeruginosa* and *Acinetobacter* spp., and in the case of critical patients infected with *P. aeruginosa*, the dose of meropenem must be increased to 1 g administered for every 6 h. Vancomycin-resistant enterococci produce extremely difficult to treat infections, the only useful antibiotic being daptomycin. Tigecycline has been approved for the treatment of complicated intra-abdominal infections caused by *Citrobacter freundii, Enterobacter cloacae, E. coli, Klebsiella oxytoca, Klebsiella pneumoniae, Enterococcus faecalis (*vancomycin-susceptible), MSSA, MRSA and some anaerobic bacteria [22].

The antibiotic, which is active only against Gram-negative bacilli and anaerobic bacteria, is metronidazole, for which no resistance has been reported.

The patients at high risk of unfavourable evolution and reserved prognosis have a high APACHE II score, poor nutritional status, significant cardiovascular diseases, immune suppression induced by medicines or by co-morbidities, while the infection source cannot be controlled. The predictive factors of therapeutic failure include the duration of the evolution prior to hospital admission, more than 2 days of presurgical treatment, as well as the presence of the MDRO. These patients should be treated similarly to those with hospital-acquired infections with carbapenems and vancomycin, but also considering the local antibiotic resistance.

The antibiotic treatment must be administered until the resolution of the clinical signs of infection (normalisation of the thermal curve, restoration of the intestinal transit) and normalisation of the biological inflammatory syndrome.

In cases with recurrent intra-abdominal infections, the diagnosis must be reassessed after 5–7 days of treatment and the investigations should be broadened (echography, CT). Often, the antibiotic therapy must be adjusted or a new surgical intervention is required in order to eliminate the site of infection.
