Identification of antibiotic consumption targets for the management of Clostridioides difficile infection in hospitals- a threshold logistic modelling approach

Figures & data

Figure 1. Monthly hospital-onset, healthcare-associated (HOHA) incidence (thick line, no. Of cases/1000 OBD) versus use of fluoroquinolones (thin line, DDD/1000 OBD), January 2015 to December 2021.

Figure 2. Monthly hospital-onset, healthcare-associated (HOHA) incidence (thick line, no. Of cases/1000 OBD) versus use of piperacillin-tazobactam (thin line, DDD/1000 OBD), January 2015 to December 2021.

Figure 3. The empirical cumulative distribution function for hospital-onset, healthcare-associated (HOHA) CDI historical data. The solid vertical line represents the 85th percentile (0.2645 cases/1000 OBD).

Figure 4. Receiver operator characteristic (ROC) chart showing the true positive classification rate against the false positive classification rate at different probability cutoff thresholds. The area under the curve (AUC) is an aggregate measure of performance across all possible classification thresholds.

Figure 5. The cumulative CDI incidence rates relative to fluoroquinolone and piperacillin-tazobactam use being above or below their respective thresholds.

Table 1. Threshold logistic results in modeling hospital-onset, healthcare-associated (HOHA) CDI incidence rate at the 85^th percentile, January 2015 to December 2021.

Predictor variable	Lag	Median (IQR)	Threshold (95% Confidence Limit)*	Relation to threshold	Coefficient (95% CI)	p-value	Odds Ratio (95% CI)
Constant	NA	NA	NA	NA	−2.849 (−4.010 to −1.687)	0.0034	0.058 (0.018 to 0.185)
Fluoroquinolones use (DDD/1000 OBD)	3	64.43 (53.58 to 76.39)	84.82 (83.25 to 84.82)	Above	0.123 (0.017 to 0.228)	0.0226	1.131 (1.017 to 1.256)
Piperacillin-tazobactam use (DDD/1000 OBD)	1	59.55 (48.48 to 67.50)	53.99 (43.80 to 70.08)	Above	0.098 (0.020 to 0.176)	0.0137	1.103 (1.020 to 1.192)

*95% confidence limit around the optimized threshold value derived using a one-at-a-time (OAT) sensitivity analysis approach; IQR, interquartile range; NA, not applicable.

Table 2. Risk scores for CDI incidence rate exceeding the 85th percentile for 2020 and 2021.

Date	HOHA CDI (cases/1000 OBD)	Fluoroquinolones use (DDD/1000 OBD) at Lag 3	Piperacillin- tazobactam (DDD/1000 OBD) at Lag 1	HOHA CDI Observed Above Median (0.1268 (cases/1000 OBD)	HOHA CDI Observed Above 85th Percentile (0.2645 (cases/1000 OBD)	Predicted Probability HOHA CDI > 85th Percentile	Coded Alert Signal
January 2020	0.3124	75.3486	51.5024	Above	Above	0.0548	Low
February 2020	0.0989	61.4988	53.0375	Below	Below	0.0548	Low
March 2020	0.1116	81.3046	55.5658	Below	Below	0.0633	Medium
April 2020	0.1536	81.9790	62.8667	Above	Below	0.1215	Medium
May 2020	0.0630	58.8139	70.0846	Below	Below	0.2190	Medium
June 2020	0.3647	96.5792	59.3821	Above	Above	0.2941	Medium
July 2020	0.3332	108.5938	59.7163	Above	Above	0.6531	High
August 2020	0.0534	61.1416	57.9710	Below	Below	0.0788	Medium
September 2020	0.0550	72.5963	53.9901	Below	Below	0.0548	Low
October 2020	0.2519	60.0117	54.9952	Above	Below	0.0601	Medium
November 2020	0.2516	51.1270	60.1860	Above	Below	0.0961	Medium
December 2020	0.1974	78.5231	61.9743	Above	Below	0.1124	Medium
January 2021	0.0944	58.2552	66.1878	Below	Below	0.1607	Medium
February 2021	0.3146	59.6880	59.7643	Above	Above	0.0926	Medium
March 2021	0.2520	52.6965	61.8441	Above	Below	0.1112	Medium
April 2021	0.1062	54.5710	69.8339	Below	Below	0.2149	Medium
May 2021	0.1452	37.3735	73.1200	Above	Below	0.2741	Medium
June 2021	0.0973	93.3579	63.6442	Below	Below	0.2987	High
July 2021	0.2843	68.8383	80.6035	Above	Above	0.4402	High
August 2021	0.1784	52.7838	67.7126	Above	Below	0.1819	Medium
September 2021	0.2323	59.8199	64.5071	Above	Below	0.1397	Medium
October 2021	0.4859	71.2120	70.4928	Above	Above	0.2260	Medium
November 2021	0.2748	50.1003	67.0806	Above	Above	0.1728	Medium
December 2021	0.5006	57.0937	83.6626	Above	Above	0.5148	High

HOHA: hospital-onset, healthcare-associated; CDI: Clostridioides difficile infection; DDD: defined daily doses; OBD: occupied bed-days.

Table 3. What-if threshold logistic model exploration.

Date	Fluoroquinolones use (DDD/1000 OBD) at Lag 3*	Piperacillin- tazobactam (DDD/1000 OBD) at Lag 1*	Predicted HOHA CDI Level	Predicted HOHA CDI Level + 1 Standard Deviation (SD)	Predicted Probability HOHA CDI > 85th Percentile	Coded Alert Signal
January 2022	73.7587	86.1628	0.2178	0.2381	0.5755	High
February 2022	66.4040	55.0000	0.1282	0.1486	0.0601	Medium
March 2022	75.1536	53.0000	0.1253	0.1457	0.0548	Low
April 2022	94.0000	63.0000	0.1877	0.2080	0.3020	High

*The cells that are highlighted in bold fonts represent months where we can substitute a range of possible lagged fluoroquinolone and piperacillin-tazobactam values since they have not yet been observed in the data history.

Table 4. HOHA CDI incidence rate distribution when antibiotic use is below/above thresholds.

	Months	Months (%)	Normalized Months (%)	HOHA CDI (Mean)	HOHA CDI (SEM)^†	Difference in HOHA CDI Mean (σ)*	Expected Reduction in HOHA CDI Cases for 2021 (95% CI)**
Fluoroquinolones use (DDD/1000 OBD) ≤ threshold	69	85.2%	41.1%	0.151	0.012
Piperacillin-tazobactam use (DDD/1000 OBD) ≤ threshold	32	38.6%	18.6%	0.129	0.013
Both Antibiotics ≤ threshold	25	83.3%	40.2%	0.136	0.015
Fluoroquinolones use (DDD/1000 OBD) > threshold	12	14.8%	15.9%	0.167	0.034	0.016	0.16
Piperacillin-tazobactam use (DDD/1000 OBD) > threshold	51	61.4%	66.1%	0.168	0.016	0.038	1.59
Both Antibiotics > threshold	5	16.7%	17.9%	0.251	0.054	0.115	1.30
						4.85% (0.82%)	3.06 (2.04 to 4.07)

*σ is the estimated standard error.

**63 HOHA CDI cases reported in year 2021.

^†SEM is the standard error of the mean.

Table 5. Estimated reduction in the number of cases of studied pathogens.

Pathogens	Total Cases in 2021	Expected Reduction in Cases	Expected Mean Incidence Reduction (σ)**
HOHA CDI	63	3	4.85% (0.82%)
MRSA	56	2	3.04% (1.12%)
Reduction in gram positives (HOHA CDI and MRSA)*			7.90% (1.94%)
ESBL-producing E. coli	71	3	4.12% (0.60%)
Overall reduction in the studied pathogens*			12.02% (2.54%)

*The reduction is weighted by the number of cases for each pathogen.

**σ is the estimated standard error.