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The methodological quality of guidelines for hospital-acquired pneumonia and ventilator-associated pneumonia: A systematic review

Ambaras Khan R, Aziz Z

J Clin Pharm Ther, 2018 Aug;43(4):450-459.
PMID: 29722052 DOI: 10.1111/jcpt.12696

WHAT IS KNOWN AND OBJECTIVES: Clinical practice guidelines serve as a framework for physicians to make decisions and to support best practice for optimizing patient care. However, if the guidelines do not address all the important components of optimal care sufficiently, the quality and validity of the guidelines can be reduced. The objectives of this study were to systematically review current guidelines for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), evaluate their methodological quality and highlight the similarities and differences in their recommendations for empirical antibiotic and antibiotic de-escalation strategies.
METHODS: This review is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Electronic databases including MEDLINE, CINAHL, PubMed and EMBASE were searched up to September 2017 for relevant guidelines. Other databases such as NICE, Scottish Intercollegiate Guidelines Network (SIGN) and the websites of professional societies were also searched for relevant guidelines. The quality and reporting of included guidelines were assessed using the Appraisal of Guidelines for Research and Evaluation II (AGREE-II) instrument.
RESULTS AND DISCUSSION: Six guidelines were eligible for inclusion in our review. Among 6 domains of AGREE-II, "clarity of presentation" scored the highest (80.6%), whereas "applicability" scored the lowest (11.8%). All the guidelines supported the antibiotic de-escalation strategy, whereas the majority of the guidelines (5 of 6) recommended that empirical antibiotic therapy should be implemented in accordance with local microbiological data. All the guidelines suggested that for early-onset HAP/VAP, therapy should start with a narrow spectrum empirical antibiotic such as penicillin or cephalosporins, whereas for late-onset HAP/VAP, the guidelines recommended the use of a broader spectrum empirical antibiotic such as the penicillin extended spectrum carbapenems and glycopeptides.
WHAT IS NEW AND CONCLUSIONS: Expert guidelines promote the judicious use of antibiotics and prevent antibiotic overuse. The quality and validity of available HAP/VAP guidelines would be enhanced by improving their adherence to accepted best practice for the management of HAP and VAP.

Matched MeSH terms: Pneumonia, Ventilator-Associated/drug therapy*
A retrospective study of antibiotic de-escalation in patients with ventilator-associated pneumonia in Malaysia

Khan RA, Aziz Z

Int J Clin Pharm, 2017 Aug;39(4):906-912.
PMID: 28643112 DOI: 10.1007/s11096-017-0499-2

Background Antibiotic de-escalation is an important strategy to conserve the effectiveness of broad-spectrum antibiotics. However, the outcome of this strategy for the treatment of ventilator-associated pneumonia (VAP) has not been widely studied in developing countries. Objectives To evaluate the outcome on intensive care unit (ICU) mortality, 28 days mortality, and length of ICU stay among VAP patients who receive de-escalation therapy. Setting This study was conducted in an ICU of a Malaysian public hospital. Method The electronic medical records of patients who developed VAP in the ICU were retrieved and relevant data was collected. Records of antibiotic prescriptions were also reviewed to collect the details of changes to antibiotic therapy (de-escalation). Main outcome measure Impact of antibiotic de-escalation on mortality. Results The mean age of the 108 patients was 46.2 ± 18.2 years; the majority being males (80%). The antibiotic de-escalation rate was about 30%. Out of this, 84% involved a change from broad to narrow-spectrum antibiotics and the remaining, withdrawal of one or more antibiotics. ICU mortality was 23% while 28 days mortality was 37%. There was no statistically significant difference in mortality rate, survival probability and the mean length of ICU stay between the de-escalation and the non-de-escalation group. However, patients with Simplified Acute Physiology Score II of ≥50 were significantly associated with ICU mortality and 28 days mortality. Conclusions In VAP patients, antibiotic de-escalation provides an opportunity to promote the judicious use of antibiotics without affecting the clinical outcomes.

Matched MeSH terms: Pneumonia, Ventilator-Associated/drug therapy*
Efficacy and safety of cefepime in late-onset ventilator-associated pneumonia in infants: a pilot randomized and controlled study

Shahid SK

Ann Trop Med Parasitol, 2008 Jan;102(1):63-71.
PMID: 18186979 DOI: 10.1179/136485908X252151

Multidrug-resistant organisms cause late-onset ventilator-associated pneumonia (VAP). In a pilot, randomized and controlled study, the efficacy and safety of cefepime, in late-onset VAP in infants, have now been evaluated in Malaysia. Thirty children aged <1 year with late-onset VAP (i.e. VAP occurring 5 or more days after intubation) were randomized to receive cefepime or, as a control, ceftazidime. The clinical responses and the microbiological clearance of tracheal aspirates were evaluated in each arm. Adverse events, if any, were monitored clinically and by blood tests. Ten of the 15 children given cefepime and five of the 15 given ceftazidime showed a satisfactory clinical response (P<0.1). Cefepime appeared significantly better at clearing polymicrobial infections from tracheal aspirates. There were no fatalities in the cefepime arm but three in ceftazidime (P<0.1). The mean (S.E.) durations of antibiotic use were 9.4 (1.5) days for cefepime and 7.6 (1.0) days for ceftazidime (P>0.05). No serious adverse effects were observed in either arm. In conclusion, in late-onset VAP in infants, cefepime monotherapy appears to be at least as effective and safe as ceftazidime monotherapy, with better microbiological clearance.

Matched MeSH terms: Pneumonia, Ventilator-Associated/drug therapy*
Antibiotic resistance and sensitivity pattern of Metallo-β-Lactamase Producing Gram-Negative Bacilli in ventilator-associated pneumonia in the intensive care unit of a public medical school hospital in Bangladesh

Nusrat T, Akter N, Rahman NAA, Godman B, D Rozario DT, Haque M

Hosp Pract (1995), 2020 Aug;48(3):128-136.
PMID: 32271642 DOI: 10.1080/21548331.2020.1754687

BACKGROUND: Ventilator-associated pneumonia (VAP) is the most common nosocomial infection in intensive care units (ICU), accounting for 25% of all ICU infections. Antimicrobial resistance is increasing and becoming a significant health problem worldwide, increasing hospital length of stay, mortality and costs. Identifying antibiotic resistance patterns in VAP is important as this can cause outbreaks in ICUs. To date, there have been limited studies assessing this in Bangladesh. Consequently, the primary objective of this research was to study the species of bacterial growth and to determine the antibiotic resistance patterns of Metallo-β-Lactamase (MBL) producing gram-negative bacilli among ICU patients with VAP in a public medical school hospital, Bangladesh. In addition, identify the factors associated with a positive culture to provide future guidance.
METHOD: Cross-sectional study performed in the Chattogram Medical College Hospital, Bangladesh. Mueller Hinton agar plates were used for antibiotic sensitivity testing by the Kirby-Buer disc diffusion test.
RESULTS: Among 105 clinically suspected VAP cases, qualitative cultures were positive in 95 (90%) of them. The most common bacteria identified were Acinetobacter spp. (43.2%), Klebsiella spp. (20%) and Pseudomonas spp. (18.9%). A positive culture was not associated with patients' age or gender. Among 41 isolated Acinetobacter spp., 38 (92.7%) were resistant to gentamicin followed by 36 (87.8%) to ceftriaxone. Among 24 isolated Klebsiella spp., 22 (83.3%) were resistant to ceftriaxone. Among 18 isolated Pseudomonas spp., 16 (88.8%) were resistant to ciprofloxacin, and 13 (72.2%) were resistant to ceftriaxone. Among nine isolated E.coli, all were resistant to ceftriaxone and ciprofloxacin. All four Proteus spp. (100%) isolated were resistant to ciprofloxacin. Additionally, phenotype MBL producing was 65.22% and genotype was 45.65% among imipenem resistant pathogens. Imipenem resistant pathogens were sensitive to amoxyclav, amikacin¸ azithromycin, ceftazidime, ceftriaxone, colistin and gentamycin.
CONCLUSION: A positive culture was detected in 90% of VAP patients, but it was not associated with the patients' age and gender. The most common bacteria identified were Acinetobacter spp., Klebsiella spp. and Pseudomonas spp., where the majority of these were resistant to ceftriaxone. The results are being used to provide future guidance on the empiric management of VAP in this hospital.

Matched MeSH terms: Pneumonia, Ventilator-Associated/drug therapy
Pharmacokinetic/Pharmacodynamics-Optimized Antimicrobial Therapy in Patients with Hospital-Acquired Pneumonia/Ventilator-Associated Pneumonia

Sulaiman H, Abdul-Aziz MH, Roberts JA

Semin Respir Crit Care Med, 2017 06;38(3):271-286.
PMID: 28578552 DOI: 10.1055/s-0037-1602716

Hospital-acquired pneumonia and ventilator-associated pneumonia continue to cause significant morbidity and mortality. With increasing rates of antimicrobial resistance, the importance of optimizing antibiotic treatment is key to maximize treatment outcomes. This is especially important in critically ill patients in intensive care units, in whom the infection is usually caused by less susceptible organisms. In addition, the marked physiological changes that can occur in these patients can cause serious changes in antibiotic pharmacokinetics which in turn alter the attainment of therapeutic drug exposures. This article reviews the various aspects of the pharmacokinetic changes that can occur in the critically ill patients, the barriers to achieving therapeutic drug exposures in pneumonia for systemically delivered antibiotics, the optimization for commonly used antibiotics in hospital- and ventilator-associated pneumonia, the agents that should be avoided in the treatment regimen, as well as the use of adjunctive therapy in the form of nebulized antibiotics.

Matched MeSH terms: Pneumonia, Ventilator-Associated/drug therapy*
Comparative efficacy and safety of treatment options for MDR and XDR Acinetobacter baumannii infections: a systematic review and network meta-analysis

Kengkla K, Kongpakwattana K, Saokaew S, Apisarnthanarak A, Chaiyakunapruk N

J Antimicrob Chemother, 2018 Jan 01;73(1):22-32.
PMID: 29069421 DOI: 10.1093/jac/dkx368

Objectives: To comprehensively compare and rank the efficacy and safety of available treatment options for patients with MDR and XDR Acinetobacter baumannii (AB) infection.
Methods: We searched PubMed, Embase and the Cochrane register of trials systematically for studies that examined treatment options for patients with MDR- and XDR-AB infections until April 2016. Network meta-analysis (NMA) was performed to estimate the risk ratio (RR) and 95% CI from both direct and indirect evidence. Primary outcomes were clinical cure and microbiological cure. Secondary outcomes were all-cause mortality and nephrotoxic and non-nephrotoxic adverse events.
Results: A total of 29 studies with 2529 patients (median age 60 years; 65% male; median APACHE II score 19.0) were included. Although there were no statistically significant differences between treatment options, triple therapy with colistin, sulbactam and tigecycline had the highest clinical cure rate. Colistin in combination with sulbactam was associated with a significantly higher microbiological cure rate compared with colistin in combination with tigecycline (RR 1.23; 95% CI 1.03-1.47) and colistin monotherapy (RR 1.21; 95% CI 1.06-1.38). No significant differences in all-cause mortality were noted between treatment options. Tigecycline-based therapy also appeared less effective for achieving a microbiological cure and is not appropriate for treating bloodstream MDR- and XDR-AB infections.
Conclusions: Combination therapy of colistin with sulbactam demonstrates superiority in terms of microbiological cure with a safety profile similar to that of colistin monotherapy. Thus, our findings support the use of this combination as a treatment for MDR- and XDR-AB infections.

Matched MeSH terms: Pneumonia, Ventilator-Associated/drug therapy
A PROspective study on the Usage patterns of Doripenem in the Asia-Pacific region (PROUD study)

Mustafa M, Chan WM, Lee C, Harijanto E, Loo CM, Van Kinh N, et al.

Int J Antimicrob Agents, 2014 Apr;43(4):353-60.
PMID: 24636429 DOI: 10.1016/j.ijantimicag.2014.01.017

Doripenem is approved in the Asia-Pacific (APAC) region for treating nosocomial pneumonia (NP) including ventilator-associated pneumonia (VAP), complicated intra-abdominal infections (cIAIs) and complicated urinary tract infections (cUTIs). Clinical usage of doripenem (500mg intravenously, infused over 1h or 4h every 8h for 5-14 days) in APAC was evaluated in a prospective, open-label, non-comparative, multicentre study of inpatients (≥18 years) with NP, VAP, cIAI or cUTI. A total of 216 [intention-to-treat (ITT)] patients received doripenem: 53 NP (24.5%); 77 VAP (35.6%); 67 cIAI (31.0%); and 19 cUTI (8.8%). Doripenem MIC90 values for Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli and Klebsiella pneumoniae were 32, 32, 0.094 and 0.64μg/mL, respectively. Doripenem was used most commonly as monotherapy (86.6%) and as second-line therapy (62.0%). The clinical cure rate in clinically evaluable patients was 86.7% at the end of therapy (EOT) and 87.1% at test of cure (TOC) (7-14 days after EOT). In the ITT population, overall clinical cure rates were 66.2% at EOT and 56.5% at TOC. The median duration of hospital stay, intensive care unit (ICU) stay and mechanical ventilation was 20, 12 and 10 days, respectively. Of 146 discharged patients, 7 were re-admitted within 28 days of EOT; 1 VAP patient was re-admitted to the ICU. The all-cause mortality rate was 22.7% (49/216). The most common treatment-related adverse events were diarrhoea (1.4%) and vomiting (1.4%). Doripenem is a viable option for treating APAC patients with NP, VAP, cIAI or cUTI. [ClinicalTrials.gov: NCT 00986102].

Matched MeSH terms: Pneumonia, Ventilator-Associated/drug therapy*