**2.5. Meningitis**

The antibiotic treatment must be urgently initiated, immediately after blood collection for blood culture and after performing the lumbar puncture. Delayed administration of the first dose of antibiotic is associated with an aggravated prognosis, and it is a strong independent factor of increased mortality, exceeding the importance of disease severity upon hospital admission and of the isolation of a penicillin-resistant strain.

The most frequent cause of delayed antibiotic therapy is the missed diagnosis due to an atypical form of meningitis (absence of fever, headache or neck stiffness). Another possible cause of temporization is represented by scheduling the imagistic investigation immediately after admitting the patient in whom the spinal tap is not safe: risk of a cerebral hernia after 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.

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

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,

The antibiotic, which is active only against Gram-negative bacilli and anaerobic bacteria, is

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 nor-

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

The antibiotic treatment must be urgently initiated, immediately after blood collection for blood culture and after performing the lumbar puncture. Delayed administration of the first dose of antibiotic is associated with an aggravated prognosis, and it is a strong independent factor of increased mortality, exceeding the importance of disease severity upon hospital

The most frequent cause of delayed antibiotic therapy is the missed diagnosis due to an atypical form of meningitis (absence of fever, headache or neck stiffness). Another possible cause of temporization is represented by scheduling the imagistic investigation immediately after admitting the patient in whom the spinal tap is not safe: risk of a cerebral hernia after

association of vancomycin.

24 Current Topics in Intensive Care Medicine

MRSA and some anaerobic bacteria [22].

metronidazole, for which no resistance has been reported.

malisation of the biological inflammatory syndrome.

admission and of the isolation of a penicillin-resistant strain.

eliminate the site of infection.

**2.5. Meningitis**

*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 pneumococcus and coagulase-negative staphylococci.

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

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 intravenous administration.

The lumbar puncture should be repeated after the first 24–36 h from the initiation of the treatment in order to assess CSF cytological, biochemical and bacteriological changes.

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

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

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

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

**Hospital-acquired bacterial meningitis (HABM)** may be the result of an invasive procedure (craniotomy, insertion of internal or external ventricular catheter, lumbar puncture, intrathecal medication, spinal anaesthesia), of a complicated cranial trauma or, in more rare cases, of an infectious metastasis in patients with hospital-acquired bacteraemia. Such meningitis is caused by microorganisms with different spectra from community-acquired cases, and the disease is the result of particular pathogenetic mechanisms.

depending on the local chemotherapeutics susceptibility profiles of Gram-negative bacilli. The empirical treatment in skull base fracture or early after ENT surgery includes vancomycin plus a third-generation cephalosporin (cefotaxime, ceftriaxone). After isolating the involved pathogen, antimicrobial therapy is changed for an optimal management. Linezolid and daptomycin are effective in staphylococcal meningitis; linezolid has good pharmacoki-

Infections and Multidrug-Resistant Pathogens in ICU Patients

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

27

The initiation of empirical treatment is recommended in all patients with post-surgical signs of meningitis; this is withdrawn after 72 h in case the results of CSF cultures are negative. The treatment must be individualised, especially in patients previously treated with antibiotics, in

Given the emergence of MDR Gram-negative bacilli, the antimicrobial therapy of HABM caused by these pathogens becomes problematic. This is especially true in cases of HABM caused by *Acinetobacter baumannii* species, bacteria with acquired resistance to third- and fourth-generation cephalosporins and even to carbapenems. The treatment of *Acinetobacter* meningitis includes meropenem associated with an aminoglycoside administered intra-ventricularly or intrathecally. If the identified isolate is resistant to carbapenems, intra-ventricular or intrathecal administration of colistin or polymyxin B will be given instead of meropenem. Treatment protocols recommended depending on the pathogenesis of the infectious process:

• *Infection after neurosurgical procedure—*Gram-negative bacilli (including *P. aeruginosa*), *Staphylococcus aureus* and coagulase-negative staphylococci (*S. epidermidis*) may be involved.

• *Ventricular or lumbar catheter—*coagulase-negative staphylococci, *S. aureus*, Gram-negative bacilli (*P. aeruginosa*) and *Propionibacterium acnes* may be present. Vancomycin plus cefepime

• *Penetrating trauma: S. aureus*, coagulase-negative staphylococci, Gram-negative bacilli.

• *Skull base fracture: Streptococcus pneumoniae*, *Haemophilus influenzae*, *Streptococcus pyogenes*. Vancomycin plus a third-generation cephalosporin (ceftriaxone or cefotaxime) is

With the increasing incidence of MRSA, skin and soft tissue infections require more frequent admission of patients presenting tissue necrosis, fever, hypotension, intense pain, altered consciousness, respiratory, hepatic or renal failure, to the ICU. When choosing the therapeutic scheme, the possibility of a polymicrobial infection must be considered, with consecutive need to cover not only MRSA but also Gram-negative and anaerobic bacteria. An inadequate initial empirical treatment is associated with prolonged evolution and hospital stay [25].

Perianal infections and abscesses, infected decubitus ulcers, and moderate and severe infections of the diabetic foot frequently involve multiple aetiologies and require coverage for

whom the treatment is continued despite the negative results of cultures.

Vancomycin plus cefepime or meropenem are recommended.

Vancomycin plus cefepime or meropenem is administered.

or meropenem are recommended.

**2.6. Infections of the skin and soft tissues**

recommended.

netic properties—CSF penetration is around 80%.

Bacterial meningitis is a redoubtable complication of craniotomy, occurring in 0.8–1.5% of the patients who undergo this procedure. One-third of the post-craniotomy meningitis cases develop during the first week after the surgical intervention, another third during the second week and one-third after the second week from the intervention, sometimes even years after the surgical procedure. The risk of post-surgical meningitis may be minimised by the attentive use of surgical techniques, especially those which decrease the possibility of liquid fistulae. Other factors associated with meningitis after craniotomy include concomitant infection at the incision site and duration of procedure exceeding 4 h.

The incidence of meningitis associated with internal ventricular catheters (cerebrospinal shunt) used in the treatment of hydrocephaly varies between 4 and 17%. The most important causative factor is the colonisation of the catheter at the time of insertion so that most infections become manifest in less than 1 month from the procedure.

External ventricular catheters are used to monitor intra-cranial pressure or to temporarily deviate the CSF if there is an obstruction in the system or as a treatment component in cases of infection of the internal catheter. The rate of external catheter-associated infection is around 8%.

The incidence of meningitis after moderate or severe cranial trauma is 1.4%. The open cranial trauma is encountered in 5% of cranial trauma and is complicated by meningitis in 2–11% of cases. Most patients in whom meningitis occurs as a complication of closed cranial trauma present a skull base fracture, which creates a communication between the sub-arachnoid space and the sinus cavities, posing an infection risk of up to 25%. The average time interval between the trauma and the onset of meningitis is 11 days. The CSF leak is the major risk factor, even though most post-traumatic leaks are not diagnosed. Most fistulae resolve spontaneously within 7 days, a surgical intervention is recommended if the breach persists. The cranial trauma is the most frequent cause of recurrent meningitis.

The diagnostic procedure relies on neuroimagistic investigations, CSF analysis (cell count, biochemical tests for glucose, proteins, Gram staining, cultures) and blood cultures. Neuroimagistics is indicated in most patients as it allows the ventricular size evaluation and brings information on a possible poor functioning of the shunt or the presence of residual catheters after previous surgical interventions.

The most frequently encountered bacteria in these cases are Gram-negative bacilli (*Klebsiella pneumoniae*, *Pseudomonas aeruginosa*), *S. aureus* and coagulase-negative staphylococci.

The empirical antibiotic therapy in HABM depends on the pathogenesis of the infectious process. In patients with meningitis occurring after neurosurgical interventions, or in patients with long-term hospitalisation after open cranial trauma or skull base fractures, vancomycin is associated with cefepime, ceftazidime or meropenem; the second antibiotic is selected depending on the local chemotherapeutics susceptibility profiles of Gram-negative bacilli. The empirical treatment in skull base fracture or early after ENT surgery includes vancomycin plus a third-generation cephalosporin (cefotaxime, ceftriaxone). After isolating the involved pathogen, antimicrobial therapy is changed for an optimal management. Linezolid and daptomycin are effective in staphylococcal meningitis; linezolid has good pharmacokinetic properties—CSF penetration is around 80%.

The initiation of empirical treatment is recommended in all patients with post-surgical signs of meningitis; this is withdrawn after 72 h in case the results of CSF cultures are negative. The treatment must be individualised, especially in patients previously treated with antibiotics, in whom the treatment is continued despite the negative results of cultures.

Given the emergence of MDR Gram-negative bacilli, the antimicrobial therapy of HABM caused by these pathogens becomes problematic. This is especially true in cases of HABM caused by *Acinetobacter baumannii* species, bacteria with acquired resistance to third- and fourth-generation cephalosporins and even to carbapenems. The treatment of *Acinetobacter* meningitis includes meropenem associated with an aminoglycoside administered intra-ventricularly or intrathecally. If the identified isolate is resistant to carbapenems, intra-ventricular or intrathecal administration of colistin or polymyxin B will be given instead of meropenem.

Treatment protocols recommended depending on the pathogenesis of the infectious process:

