OBJECTIVE: This study aimed to appraise clinical practice guidelines (CPGs) for the treatment of carbapenem-resistant Gram-negative Bacilli (CRGNB) infections and to summarise the recommendations.
METHODS: A systematic search of the literature published from January 2012 to March 2023 was undertaken to identify CPGs related to CRGNB infections treatment. The methodological and reporting quality of eligible CPGs were assessed using six domains of the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool and seven domains of the Reporting Items for practice Guidelines in HealThcare (RIGHT) checklist. Basic information and recommendations of included CPGs were extracted and compared.
RESULTS: A total of 21 CPGs from 7953 relevant articles were included. The mean overall AGREE II score was 62.7%, and was highest for \"clarity of presentation\" (90.2%) and lowest for \"stakeholder involvement\" (44.8%). The overall reporting quality of all of the CPGs was suboptimal, with the proportion of eligible items ranging from 45.7 to 85.7%. The treatment of CRGNB infections is related to the type of pathogen, the sensitivity of antimicrobial agents, and the site of infection. In general, the recommended options mainly included novel β-lactam/ β-lactamase inhibitors, cefiderocol, ampicillin-sulbactam (mainly for carbapenem-resistant Acinetobacter baumannii [CRAB]), and combination therapy, involving polymyxin B/colistin, tigecycline (except for carbapenem-resistant Pseudomonas aeruginosa), aminoglycosides, carbapenems, fosfomycin, and sulbactam (mainly for CRAB).
CONCLUSIONS: The methodological and reporting quality of CPGs for the treatment of CRGNB infections are generally suboptimal and need further improvement. Both monotherapy with novel drugs and combination therapy play important roles in the treatment.

Appendicitis is a frequent clinical condition in normal children that may be complicated by community-acquired secondary peritonitis (CASP). We evaluated the potential efficacy of different drugs for initial treatment of this condition, as recommended by recent Consensus Conference and Guidelines for paediatric patients. Susceptibility to ampicillin-sulbactam, ertapenem, gentamycin, piperacillin, piperacillin-tazobactam, vancomycin, and teicoplanin was evaluated according to EUCST 2012 recommendations in aerobic bacteria isolated from peritoneal fluid in CASP diagnosed from 2005 to 2011 at \'Istituto Giannina Gaslini\', Genoa, Italy. A total of 114 strains were analysed: 83 E. coli, 15 P. aeruginosa, 6 Enterococci, and 10 other Gram-negatives. Resistance to ampicillin-sulbactam was detected in 37% of strains, while ertapenem showed a potential resistance of 13% (all P. aeruginosa strains). However, the combination of these drugs with gentamicin would have been increased the efficacy of the treatment to 99 and 100%, respectively. Resistance to piperacillin-tazobactam was 3%, while no strain was resistant to meropenem. Our data suggest that monotherapy with ampicillin-sulbactam or ertapenem for community-acquired secondary peritonitis would present a non-negligible rate of failure, but the addition of gentamycin to these drugs could reset to zero this risk. On the contrary, monotherapy with piperacillin-tazobactam or meropenem is highly effective.

For in vitro susceptibility tests with cefoperazone and sulbactam (a beta-lactamase inhibitor), 75/30-micrograms disks may be used with the interpretive zone size breakpoints that are currently used for 75-micrograms cefoperazone disks. For dilution tests, a 2:1 ratio of cefoperazone to sulbactam is recommended. For quality control purposes, MIC limits that are used to monitor cefoperazone tests were also applied to tests with the combination of drugs. For gram-negative control strains, zone size limits were calculated to be 1 mm smaller than those used for cefoperazone disks. To monitor the sulbactam portion of the combination, Acinetobacter calcoaceticus subsp. anitratus ATCC 43498 was selected; zones with 75/30-micrograms disks were 26 to 32 mm in diameter, and broth microdilution MICs ranged from 1.0/0.5 to 8.0/4.0 micrograms/ml. With cefoperazone alone, MICs for Acinetobacter calcoaceticus subsp. anitratus were 16 to 64 micrograms/ml and zones ranged from 14 to 18 mm in diameter. For anaerobic dilution tests, only Bacteroides thetaiotaomicron ATCC 29741 is recommended for cefoperazone-sulbactam; MICs ranged from 8.0/4.0 to 32/16 micrograms/ml.

The ampicillin-sulbactam combination was evaluated in vitro to determine the optimal susceptibility testing conditions among five combination ratios and four fixed concentrations of sulbactam. The organisms tested were markedly resistant to aminopenicillins and most other beta-lactams. The ratio of 2:1 is recommended to assure recognition of the ampicillin-sulbactam spectrum and minimize false-susceptible results among strains known to be resistant to this combination. Proposed MIC breakpoint concentrations were compatible with levels in serum achieved with recommended clinical doses. Cross-resistance analyses comparing ampicillin-sulbactam and amoxicillin-clavulanate showed comparable activity and spectra. However, the major interpretive disagreement was sufficient to require separate testing of these aminopenicillin-inhibitor combinations. The recommended ampicillin-sulbactam MIC susceptibility breakpoints are as follows: (i) less than or equal to 8.0/4.0 micrograms/ml for tests against members of the family Enterobacteriaceae, anaerobes, nonenteric gram-negative bacilli, staphylococci, Haemophilus influenzae, and Branhamella catarrhalis; (ii) the ampicillin MICs alone interpreted by National Committee for Clinical Laboratory Standards criteria should predict ampicillin-sulbactam susceptibility for the enterococci, streptococci, and Listeria monocytogenes. MIC quality control ranges were determined by multiple laboratory broth microdilution trials for the ampicillin-sulbactam 1:1 and 2:1 ratio tests.