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Published on 1 December 2002

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Treating hospital-acquired pneumonia

Francesco Blasi
MD PhD
Associate Professor
Institute of Respiratory Diseases
University of Milan
IRCCS Ospedale Maggiore Milano
Milan, Italy

Roberto Cosentini
MD
Consultant

Paolo Tarsia
MD
Consultant
Department of Emergency Medicine IRCCS Ospedale Maggiore Milano
Milan, Italy

Contact
Francesco Blasi
E:francesco.blasi@unimi.it

The most important risk factors for HAP development are shown in Table 1.(2–7) The clinical diagnosis of HAP is often difficult to establish.(8) Fever and leukocytosis in a patient with a chest radiograph showing infiltrates is certainly compatible with HAP, but also with other noninfectious aetiology such as pulmonary embolism, lung cancer and acute respiratory distress syndrome.

[[HPE06_table1_31]]

Cultures obtained by endotracheal aspirate, protected bronchial brushing or bronchoalveolar lavage may merely reflect airways colonisation. Microbial diagnosis of HAP should not be based on endotracheal aspirate cultures. Protected bronchial brushing and bronchoalveolar lavage with semiquantitative bacterial cultures appear to better reflect the aetiology. Transbronchial lung biopsy with specimen culture and histology shows high sensitivity and specificity.(9,10) Culture of pleural or empyema fluid and percutaneous lung biopsy culture prove the causative role of the bacteria identified. (Staphy-lococcus aureus cutaneous contamination should be taken into account.)

There is still controversy over whether invasive sampling by bronchoscopy has a positive impact on the outcome. Two recent studies support the use of invasive techniques in the ICU, showing a lower mortality in patients who underwent bronchoscopy sampling.(11,12)

A chest X-ray may sometimes be a useful tool supporting a specific aetiology. In necrotising pneumonia, rapid cavitation (<72 hours), is compatible with Staph. aureus or Pseudomonas aeruginosa infection, whereas delayed cavitation is seen with Klebsiella pneumoniae pneumonia.

Pathogens involved
The spectrum of pathogens involved in HAP is certainly different from that of community-acquired pneumonia and is influenced by the presence of at least three main factors:(13,14)

  • Severity of illness.
  • Presence of risk for specific pathogens.
  • Time to onset of pneumonia.

The pathogens most frequently involved in HAP are enteric Gram-negative bacilli (eg, Enterobacter spp., E. coli, Klebsiella spp.), Staph. aureus and Streptococcus pneumoniae. The role of polymicrobial aetiology of HAP has been proposed in about 50% of cases,(15,16) but a recent review questioned the aetiologic role of multiple pathogens recovery in respiratory secretion specimens.(8)

Treatment
Once the diagnosis of HAP has been made, treatment should be started immediately. Inadequate initial therapy is associated with an increased mortality,(17) and prompt use of appropriate therapy seems to be critical for patient outcome. In all cases empiric antibiotic therapy should cover a broad spectrum of pathogens, including all the “core” bacteria.

The use of monotherapy or combination therapy approaches is still controversial. Combination therapy is the traditional approach – a beta-lactam plus an aminoglycoside or a fluoroquinolone.(18,19) Vancomycin should be considered in the presence of risk factors for methicillin-resistant Staph. aureus (MRSA). Recently, innovative approaches have been suggested, such as monotherapy with new antibiotics.(20) However, combination therapy results in much lower resistance rates than monotherapy.(21) Nonsevere HAP can usually be treated with a single antibiotic if no additional risk factors are present, whereas severe HAP or patients with risk factors should be treated with combination antibiotic therapy.

Treatment of specific pathogens

Pseudomonas aeruginosa
Since HAP caused by this pathogen is associated with the worst prognosis, most physicians use combination therapy with two drugs possessing in-vitro activity against P. aeruginosa. Monotherapy may be suboptimal in treating this infection.(19) The combination of antipseudomonal beta-lactams (piperacillin/tazo-bactam, ceftazidime, imipenem/cilastatin) with an aminoglycoside (amikacin, tobramycin) is probably the most common. The rationale of such a combination relies on the synergistic effect between the two classes and the potential reduction of the development of resistance. Some concerns still remain regarding the use of aminoglycosides. This type of drug penetrates poorly into bronchopulmonary secretions and may be inactivated at low pH. Furthermore, aminoglycosides have some serious potential toxicity such as nephrotoxicity and ototoxicity. Aggressive aminoglycoside dosing followed by monitoring of drug pharmacokinetics has demonstrated a good risk/benefit ratio.(22) The association between piperacillin/tazobactam and aminoglycosides was more effective than ceftazidime/aminoglycoside or imipenem–cilastatin/ aminoglycoside combinations in terms of bacterial failures, mortality and superinfections.(18,23,24)

The carbapenems have broad-spectrum activity and resist beta-lactamase degradation; despite this excellent in-vitro activity, the response rate appears to be suboptimal when the drug is used as monotherapy. Furthermore, a high rate of detection of resistant strains has been reported, even during combination therapy with aminoglycosides.(16) Their use should probably be reserved for treatment of infections in which resistance to other beta-lactam antibiotics is proven or suspected.

Recently, new combinations of antipseudomonal beta- lactams and fluoroquinolones with anti-pseudomonal activity (ciprofloxacin and levofloxacin) have been proposed as possible alternatives. P. aeruginosa strains show similar susceptibility patterns both with ciprofloxacin and levofloxacin.(25) Neither ciprofloxacin nor levofloxacin could be used as monotherapy in pseudomonal infections – both drugs should be used in combination. A possible advantage in terms of safety could be reached with the beta-lactam/ fluoroquinolones combination.

Staphylococcus aureus infection
If Staph. aureus infection is suspected, it is advisable to know the institution-specific prevalence of methicillin- resistant organisms before antibiotic therapy is selected. Risk factors for infection caused by resistant organisms are antibiotic treatment before the onset of pneumonia, corticosteroid use and COPD. Vancomycin may be associated with a higher mortality than oxacillin in methicillin-susceptible Staph. aureus (MSSA), suggesting that beta-lactam antibiotics may be preferred to vancomycin in MSSA.(26) In the presence of documented MRSA infection, vancomycin can be used, taking into account that large use can predisposes to vancomycin-resistant Enterococcus. Linezolid and quinupristin/dalfopristin offer potentially promising activity against MRSA.

Legionella infection
Many antibiotics that present high in-vitro activity against Legionella species, including imipenem and amoxycillin/clavulanic acid, are not clinically useful in vivo. The best treatment regimen is probably a full three-week treatment with a macrolide. Resistant strains may develop if using rifampicin as sole therapy.(27) An alternative treatment regimen may be the association of second-generation fluoroquinolones (ciprofloxacin) with tetracyclines. A notable improvement in most of the new fluoroquinolones is their activity against Legionella. Their use as a single agent may be considered even if clinical data are still insufficient for a definitive indication.

Prevention
Considering that the two main processes that lead to HAP are bacterial colonisation of the oropharyngeal and gastric reservoirs and aspiration of contaminated secretions into the lower airways, the strategies for the prevention of HAP must be focused on reducing colonisation and aspiration. (28,29) Noninvasive ventilation compared with endotracheal intubation is associated with a reduction of nosocomial infections.(30) On the other hand, prophylaxis against stress ulcers with sucralfate, a cytoprotective agent with no activity on gastric pH, has been associated with a trend towards a reduction of HAP, as compared with histamine H(2)-receptor antagonists plus antacids. However, a recent large study did not show any differences between ranitidine and sucralfate prophylaxis.(31)

Some studies have shown beneficial effects of antibiotic prophylaxis in high-risk ICU patients.(6,7) The protective effects of cefuroxime 1.5g twice daily have been demonstrated in patients with closed head injury or stroke requiring prolonged mechanical ventilation.(32) However, although a brief course of antibiotics may have a beneficial effect in selected patients, widespread and prolonged use of antibiotic prophylaxis may be harmful, leading to the selection/acquisition of P. aeruginosa, Acinetobacter spp. and other potentially resistant bacteria.(33,34)

Selective decontamination of the digestive tract seems to be useful only in surgical patients – no significant effects have been shown in critically ill medical patients.(35) The use of regimens employing nonabsorbable antibiotics, oral antibiotic paste and parenteral agents to reduce gastrointestinal colonisation is not supported by risk–benefit analysis.(36,37)

Table 2 shows the main preventive strategies that may be used to reduce HAP incidence.(38)

[[HPE06_table2_32]]

Conclusion
HAP has still a major impact in terms of mortality and morbidity among hospitalised patients. Appropriate early antibiotic therapy is associated with a reduction in mortality and improved outcomes. Nonsevere HAP can usually be treated with a single antibiotic if no additional risk factors are present, whereas severe HAP or patients with risk factors should be treated with a combination antibiotic therapy approach.

Patient follow-up in terms of microbiological, clinical, and radiological monitoring is important.

Prevention strategies are critical and are based on understanding the epidemiology and pathogenesis of HAP. Routine efforts at prevention should be directed at effective surveillance and infection control programmes, including staff education, proper isolation techniques and infection control practices.

References

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