Table 1.

Characteristics of studies considering the use of antibiotics associated with increased occurrence of neonatal sepsis related to resistant bacteria.

First author (year and publication country)	Type of study	Population	Outcome	Results	Newcasttle Otawaa			Imprecision (NNH)b
					Selection (****)	Outcome (***)	Comparability (**)
Bryan34	Prospective cohort	Lack of data about the total number of hospitalization.	Evaluation of time and number of GNB infection emergence during the replacement of the antibiotic empiric treatment with gentamicin after K. pneumoniae resistant to gentamicin outbreak and the use of cefotaxime as the replaced treatment.	Resistant to 3rd generation cephalosporin GNB appeared faster and seriousness.	**	*	*	–
Calil2	Prospective cohort	Phase 1: 67 samples from 31 patients. Phase 2: 342 patients. Phase 3: 891 colonizations of 324 patients. Phase 4: nosocomial infections: 1995: 78; 1996: 74; 1997: 75; 1998: 52; 1999: 57.	Incidence of multidrug resistance considering the period before and after implementation of infection control measures, including restricted use of cefotaxime.	Reduction in the incidence of resistant bacteria infection, from 18 per year to 2 per year, from 1995 to 1999.	***	***	**	NNH = 4.9
Singh33	Prospective cohort	From 240 colonized by resistant Enterobacteria. 34 developed infection.	Risk factors related to multidrug-resistant Enterobacteria infection in patients colonized by these bacteria.	At the multivariate analyzes, the prolonged use of antibiotics was considered as a risk factor, with OR: 1.8 (CI 95%: 1.32–2.44).				NNH = 8.3
Flidel-Ramon28	Prospective cohort	Phase 1: 5661 neonates/year. Phase 2: 6255 neonates/year.	Evaluates the reduction of MR-GNB after replacement of cefotaxime to piperacillin/tazobactam.	Important reduction in incidence of MR-GNB infection.	***	***	**	NNH = 1.85
Pessoa-Silva15	Prospective cohort	13 ESBL infected patients.	Evaluates risk factors related to ESBL colonization and infection.	Strong relation with infection and colonization OR: 5.19 (CI 95%:1.58–17.08) and presents as a risk factor to colonization the use of cephalosporin + aminoglycosides. OR: 4.69.	***	***	**	–
Linkin32	Case control	4 ESBL Enterobacteria infected patients and 6 non-ESBL Enterobacteria infected patients.	Clinical risk factors to develop ESBL infection.	Previous treatment with cephalosporin duration was considered as a risk factor p = 0.2.	**	*	*	–
Crivaro30	Case control	167 patients, including 100 ESBL K. pneumoniae and/or Serratia marcescens infection.	Infected and non-infected patients by GNB producer of ESBL during an outbreak.	Duration of treatment with ampicillin and gentamicin was OR: 1.316 (CI 95%: 1.021–1.695) with p < 0.034.	**	*	–	NNH = 5.1
Huang17	Case control	22 cases and 17 controls.	Risk factors for K. pneumoniae and E. coli producer of ESBL infection.	OR: 12.8 (CI 95%: 1.1–143.8) to the previous use of 3rd generation cephalosporin.	***	***	**	NNH = 2.3
Abdel-Hady5	Prospective cohort	473 hospital admissions including 138 proved cases of sepsis related to healthcare assistance.	Neonates infected with Klebisiella pneumoniae and neonates infected with ESBL K. pneumoniae.	The use of oxymin-antibiotics had OR: 4.9 (CI 95%: 1.1–21.5) with p < 0.04.	***	***	**	NNH = 3.7
Le31	Prospective cohort	Phase 1:130 neonates. Phase 2: 120 neonates.	Clinical characteristics after altering the treatment from cefotaxime to trobamycin on empiric treatment to late sepsis.	Significative reduction in ESBL infection. OR: 33.73 (CI 95%: 1.02–1136.2) to the exposure of cephalosporin and an of OR 3.09 (CI 95%: 1.28–7.49) to each additional day using ampicillin and gentamicin and OR: 1.55 (CI 95%: 0.963–2.49) related to the prolonged use of cefotaxime and trobamycin.	***	***	**	NNH = 2.7
Murki14	Prospective cohort	Phase 1:1046 neonates. Phase 2: 1074 neonates.	Clinical characteristics before and after the restriction of cephalosporin use.	22% reduction in ESBL infection (p = 0.035), 30% cefotaxime resistant infection (p = 0.006) and 27% in ciprofloxacine resistant infection (p = 0.01).	***	***	**	NNH = 4.5
Landre-Peigne26	Prospective cohort	Phase 1: 125 neonates. Phase 2: 148 neonates.	Evaluates the incidence of multidrug-resistant bacteria’s and antibiotic use after the implementation of infection control measures.	Despite the suspicious of precocious sepsis, there was a reduction in the treatment number and a significative decrease in the incidence of resistant bacteria (p < 0.001).	***	***	**	NNH = 1.49
Tsai29	Prospective cohort	70 multidrug resistant GNB infected neonates and 306 infected by other bacteria’s type.	Risk factors to multidrug-resistant GNB infection.	3rd generation cephalosporin, vancomycin/teicoplanin and carbapenem used (p < 0.001); time >48 h to adequate the antibiotic (p < 0.001). In multivariate analyses, 3rd generation cephalosporin use OR: 5.97, OR: 5.97 (CI 95%: 2.37–15.08) and carbapenem OR: 3.60 (CI 95%: 1.26–10.29) were associated with increased risk.	***	***	**	NNH = 2.47
Yusef4	Case control	35 multidrug-resistant bacteria infected neonates (ESBL, MARSA, KPC and MR Acineto baumannii) and 16 non-infected.	Risk factors to multidrug resistant bacteria.	Previous use of vancomycin and meropenem was considered as a risk factor to KPC and MDR – A. baumannii infection (OR: 0.07).	**	**	*	NNH = 2.38

The symbol * match the score on each item evaluated from the articles.

GNB, Gram-negative bacteria; OR, Odds Ratio; CI, Confidence intervals; MR, multidrug-resistant; ESBL, producers of extended-spectrum β-lactamases; MARSA, Methicillin-resistant Sthaphylococcus aureus; KPC, Klebisiella pneumoniae carbapenemase.

^aA study can be awarded a maximum of one star for each numbered item within the selection and exposure categories. A maximum of two stars can be given for comparability. For comparability the most important factor was HAI by resistant bacteria.

^bNNH, Number of patients Needed to Harm.