Abstract
Background
Reported beta-lactam allergies often lead to avoidance of first-line antibiotics and may increase surgical complications. Cesarean sections (CSs), where prophylactic antibiotics are universally administered, offer a unique setting to assess the clinical impact of these labels on outcomes. The objective of this study was to investigate the impact of beta-lactam allergy labels on surgical site infection (SSI) rates and adherence to CS prophylactic antibiotic guidelines.
Methods
We performed a retrospective cohort study of all women undergoing CS at a secondary medical center between 2018 and 2023. Women with chorioamnionitis or missing antibiotic data were excluded. Patients were grouped by the presence or absence of a beta-lactam allergy label. For each group, we assessed 30-day SSI rates and adherence to prophylaxis guidelines (drug, dose, timing). Multivariable logistic regression identified independent predictors of SSI.
Results
Among 7,060 eligible women, 307 (4.3%) carried a beta-lactam allergy label. Not-per protocol antibiotic administered in 201/307 (65%) of labeled vs. 739/6,753 (11%) of unlabeled patients (p < 0.001), mainly due to clindamycin monotherapy (88% of inadequate regimens). SSI rates were higher among labeled patients, 20/307 (6.5%) vs. 271/6,753 (4.0%) (p = 0.031). Among all patients, SSI occurred in 266/6,733 (3.9%) receiving cefazolin-based prophylaxis, 4/64 (6.3%) with clindamycin plus gentamicin, and 21/256 (8.2%) with inadequate regimens (p = 0.003). Beta-lactam allergy labeling independently increased SSI risk (aOR 1.68, 95% CI 1.05–2.71, P = 0.031).
Conclusions
Beta-lactam allergy labels were associated with an increased risk of SSI after cesarean section, due to suboptimal selection of prophylactic antibiotics. These findings underscore the importance of accurate allergy documentation and evidence-based perioperative antimicrobial stewardship to ensure optimal prophylaxis.
Keywords: beta-lactam allergy, antibiotic prophylaxis, surgical site infection, cesarian section
Introduction
Approximately 10% of hospitalized patients report a beta-lactam allergy, yet more than 90% can safely tolerate beta-lactam after formal evaluation [1, 2]. Inaccurate allergy labels are associated with avoidance of first-line agents, unnecessary broader-spectrum antibiotic use, and adverse outcomes when given as prophylaxis in surgical patients [3–5]. Despite evidence and consensus statements supporting cefazolin use in most patients labeled as penicillin allergic [6–8], clinicians frequently continue to prescribe alternative agents for patients with reported beta-lactam allergy and rarely reassess or formally challenge the accuracy of the allergy label. Cesarean sections offer a unique opportunity to study the consequences of these practices as antibiotic prophylaxis is universally administered, and regimen selection is tightly protocolized.
Cesarean section (CS) is one of the most frequently performed surgical procedures worldwide. In Israel, CSs account for approximately 20% of deliveries in the country [9]. Women undergoing CS are at a substantially increased risk of postoperative infection, five to twenty times higher than those with vaginal births, with 5–10% complicated by surgical site infections (SSIs) [10, 11]. These infections range from superficial to deep and organ/space incisional infections, as defined by the Centers for Disease Control and Prevention (CDC)’s National Healthcare Safety Network (NHSN [12]. SSIs are associated with prolonged hospitalization, increased healthcare costs, and significant maternal morbidity [11].
Prophylactic antibiotics effectively reduce SSIs risk following both elective and non-elective CSs [13–15]. Current guidelines from the American College of Obstetricians and Gynecologists (ACOG), the CDC and the Surgical Infection Society recommend administration of a single preoperative dose of a first-generation cephalosporin, typically cefazolin, within one hour of incision, with the addition of azithromycin in non-elective cases [16–23]. For patients with true cefazolin allergy, clindamycin combined with gentamicin is advised as an alternative regimen [16–18]. However, this substitution is less well validated and may provide suboptimal coverage against key pathogens.
This study aimed to evaluate the impact of reported beta-lactam allergy labels on adherence to antibiotic prophylaxis guidelines in women undergoing CS and to assess their subsequent effect on SSIs rates.
Methods
This is an observational cohort retrospective study analyzing electronic medical records (EMRs) of women aged 18 years and older, who underwent elective or non-elective CSs at Meir medical center between January 2018 and September 2023. Meir medical center is a secondary hospital with 780 admission beds and approximately 1,000 CSs annually. Inclusion criteria encompassed all eligible women, excluding those with chorioamnionitis (defined as maternal fever above 39 °C or above 38 °C combined with fetal tachycardia of above 160 beats per minute) or lacking prescribed antibiotic data. Data extracted from EMRs included demographic details and clinical characteristics such as maternal and labor specifics, details of prescribed prophylactic antibiotics (names, dosages, and dates), reported beta-lactam allergies and SSI events in the 30 days post procedure.
Reported beta-lactam allergy labels were considered as the exposure variable and were defined as any documented allergy to antibiotics within the beta-lactam group, based on previous reports in the patient EMR. Mild reactions such as rashes and pruritus were categorized as mild allergic responses, whereas severe symptoms including angioedema, severe urticaria, dyspnea, and anaphylactic shock were classified as severe reactions.
Antibiotic prophylaxis regimens were considered appropriate per-protocol as follows:
For elective CSs (intact membranes, not in labor) or for women in labor without ruptured membranes: cefazolin (< 120 kg given 2 g intravenously (IV), > 120 kg given 3 g IV).
For laboring women with ruptured membranes: cefazolin (same dosages as mentioned above) plus azithromycin 500 mg IV.
Alternative regimen for patients with reported beta-lactam allergy: clindamycin 900 mg IV plus gentamicin 5 mg/kg IV plus azithromycin 500 mg IV if deemed necessary as described above. At our institution, cefazolin is recommended as first-line prophylaxis, including for most patients with a reported penicillin allergy, consistent with contemporary evidence that cefazolin can be safely administered in most patients with penicillin allergy due to its distinct side chain structure [6–8]. However, for the purposes of this study, clindamycin plus gentamicin was also considered an accepted alternative in patients with a documented beta-lactam allergy label at clinician discretion. Therefore, patients with a penicillin allergy who received either cefazolin or clindamycin plus gentamicin were classified as having received per-protocol prophylaxis. Regimens were considered not per protocol only if they fell outside these recommended options (a, b or c) or were not administered within one hour of the incision at the recommended dosages. No changes were made to the local antibiotic prophylaxis guidelines during the study period.
SSIs were defined according to CDC’s NHSN criteria as infections occurring within 30 days post-operation [12]. These were further classified into superficial incisional, deep incisional or organ/space infections (such as endometritis and intra-abdominal abscess). SSI events were identified in real-time by an infectious control specialist as part of our medical center’s infection control unit’s surveillance program. To ensure thorough monitoring, our infection control team proactively reached out to all women who underwent CSs at our medical center within 30 days post-surgery via telephone. This proactive follow-up was conducted to verify the absence of any SSI occurrence, thereby contributing to comprehensive post-operative surveillance.
The primary outcome of this study was 30-day SSIs rates among women undergoing CS. Secondary outcomes included adherence to prophylactic antibiotic guidelines including antibiotic selection, timing and dosages.
Statistics
Data analysis involved presenting the results as percentages for nominal variables and mean or median for continuous data. Comparisons between groups were made using appropriate statistical tests, such as chi-square or Fisher exact test for categorical variables and Student t-test or Mann-Whitney U-test for continuous variables. Multivariate logistic regression was employed to estimate odds ratios for SSIs, which were considered the dependent variable. Explanatory variables that were associated with SSI in the bivariate analysis with a p < 0.1 were included in the regression model, along with age, which was treated as a universal variable. The regression model was carried out twice with ENTER method: first with beta-lactam allergy as an explanatory variable, and then again with inappropriate antibiotic treatment replacing beta-lactam allergy as an explanatory variable. Goodness of fit was determined using Hosmer and Lemeshow test. Statistical significance was set at p-values < 0.05. The analysis was performed using SPSS version 27 (IBM Corp., Armonk, NY).
Results
Patient characteristics
A total of 7,060 women met inclusion criteria during study period (Fig. 1). The mean maternal age was 32.7 years (SD ± 5.7). The majority of women had a mean parity of 2.1 (SD ± 1.2 deliveries), 42.7% had a history of previous CS and the mean gestational age at delivery was 38.1 weeks (SD ± 2.4). While 307 women (4.3%) reported beta-lactam allergies (83% mild and 17% with severe reactions), there were no statistically significant differences between the allergy reported group and women without these allergy labels, in terms of maternal and labor specifics (Table 1).
Fig. 1.
Study design. Cohort selection of women undergoing cesarean surgery (2018–2023), with exclusions and stratification by beta-lactam allergy label
Table 1.
Baseline characteristics of patients
| Variable | Total (n = 7,060) |
Reported beta-lactam allergy (n = 307) |
Non-beta-lactam allergy (n = 6,753) |
P-value |
|---|---|---|---|---|
| Maternal age (years) | 32.7 ± 5.7 | 34.1 ± 5.3 | 32.6 ± 5.7 | 0.040 |
| Gravidity | 2.6 ± 1.6 | 2.7 ± 1.5 | 2.6 ± 1.6 | 0.480 |
| Parity | 2.1 ± 1.2 | 2.1 ± 1.1 | 2.1 ± 1.2 | 0.780 |
| Previous CS | 3,013 (42.7) | 126 (41.0) | 2,887 (42.7) | 0.596 |
| BMI (kg/m2) |
n = 6,940 29.9 ± 5.9 |
n = 304 29.7 ± 5.3 |
n = 6,636 30 ± 5.9 |
0.748 |
| Diabetes mellitus | 1,543 (21.9) | 66 (21.5) | 1,477 (21.9) | 0.877 |
| Gestational age at delivery (weeks ± days) | 38.1 ± 2.4 | 38.0 ± 2.5 | 38.1 ± 2.4 | 0.813 |
|
Number of fetuses Singleton birth Twin birth Triplet birth |
6,563 (93.0) 488 (6.9) 9 (0.1) |
285 (92.8) 21 (6.8) 1 (0.3) |
6,278 (93.0) 467 (6.9) 8 (0.1) |
0.825 |
| Preterm birth | 1,312 (18.6) | 64 (20.8) | 1,248 (18.5) | 0.166 |
| Active labor | 2,573 (36.4) | 117 (38.1) | 2,456 (36.4) | 0.535 |
| Second stage of labor (min) |
n = 563 10.6 ± 13.5 |
n = 21 6.5 ± 5.7 |
n = 542 10.7 ± 13.7 |
0.076 |
|
ROM No SROM AROM PROM PPROM |
4,099 (58.1) 1,498 (21.2) 869 (12.3) 104 (1.5) 490 (6.9) |
183 (59.6) 58 (18.9) 39 (12.7) 5 (1.6) 22 (7.2) |
3,916 (58.0) 1,440 (21.3) 830 (12.3) 99 (1.5) 468 (6.9) |
0.979 |
|
Duration of ROM (hours) No 0.1–5.9 6.0-11.9 12-17.9 > 18 |
4,129 (58.5) 1,058 (15.0) 762 (10.8) 304 (4.3) 807 (11.4) |
185 (60.3) 50 (16.3) 26 (8.5) 14 (4.6) 32 (10.4) |
3,944 (58.4) 1,008 (14.9) 736 (10.9) 290 (4.3) 775 (11.5) |
0.419 |
|
Amniotic fluid Clear Meconium Bloody |
6,436 (91.2) 548 (7.8) 76 (1.1) |
279 (90.9) 24 (7.8) 4 (1.3) |
6,157 (91.2) 524 (7.8) 72 (1.1) |
0.784 |
|
CS indication Elective Urgent |
2,412 (34.2) 4,646 (65.8) |
102 (33.2) 205 (66.8) |
2,312 (34.2) 4,441 (65.8) |
0.715 |
|
Anesthesia Regional General Combined |
6,306 (89.3) 676 (9.6) 78 (1.1) |
270 (87.9) 32 (10.4) 5 (1.6) |
6,036 (89.4) 644 (9.5) 73 (1.1) |
0.339 |
|
ASA score 1–2 3–5 |
6,473 (91.7) 587 (8.3) |
281 (91.5) 26 (8.5) |
6,192 (91.7) 561 (8.3) |
0.916 |
|
Wound class Clean-contaminated Contaminated |
6,505 (92.1) 555 (7.9) |
283 (92.2) 24 (7.8) |
6,222 (92.1) 531 (7.9) |
0.977 |
| Surgery duration (min) | 49.7 ± 20.2 | 49.1 ± 16.8 | 49.7 ± 20.3 | 0.816 |
Continues variables are presented as mean ± SD, and categorical variables as n (%). Diabetes mellitus- included gestational and pre-gestational diabetes mellitus; Preterm birth- delivery prior to 37 weeks; Active labor was defined as CS performed at more than 4 cm dilation,CS, Cesarean section; BMI, body mass index; ROM, rupture of membranes; SROM, spontaneous ROM;AROM, artificial ROM; PROM, pre-labor ROM; PPROM, premature PROM prior to 37 weeks of gestation; ASA, American society anesthesiologists.
Surgical site infections
Among the 7,060 cases analyzed, 291 events of SSI were identified, accounting for 4.1% of all cases (Table 2). Women who received a cefazolin-based regimen had an SSI rate of 266/6,733 (3.9%), those who received clindamycin plus gentamicin had 4/64 (6.3%), and those who were administrated an inadequate antibiotic regimen had 21/256 (8.2%) SSI rate (p = 0.003). Patients with beta-lactam allergy labels experienced higher SSI rates (6.5% vs. 4.0% in patients without reported allergies, p = 0.031). Furthermore, women with beta-lactam allergy labels had higher rates of deep infections (5.0% vs. 2.6%) and organ/space infections (60.0% vs. 49.4%), although these differences did not reach statistical significance (Table 2).
Table 2.
SSI rates and adherence to prophylactic antibiotic guidelines
| Variable | Total (n = 7,060) |
Reported beta-lactam allergy (n = 307) |
Non beta-lactam allergy (n = 6,753) |
P value |
|---|---|---|---|---|
| SSI events | 291 (4.1) | 20 (6.5) | 271 (4.0) | 0.031 |
|
SSIs classification Superficial Deep Organ-spaced |
n = 291 137 (47.1) 8 (2.7) 146 (50.2) |
n = 20 7 (35.0) 1 (5.0) 12 (60.0) |
n = 271 130 (48.0) 7 (2.6) 134 (49.4) |
0.478 |
| Not per-protocol antibiotic administration | 940 (13.3) | 201 (65.5) | 739 (10.9) | < 0.001 |
|
Inadequate antibiotic regimen Clindamycin monotherapy Azithromycin monotherapy Gentamicin monotherapy Clindamycin and azithromycin Ampicillin monotherapy Other |
256 (3.6) 153 (59.8) 24 (9.4) 21 (8.2) 19 (7.4) 15 (5.9) 24 (9.4) |
164 (53.4) 144 (87.8) 2 (1.2) 0 (0) 16 (9.8) 0 (0) 2 (1.2) |
92 (1.4) 9 (9.8) 22 (23.9) 21 (22.8) 3 (3.3) 15 (16.3) 22 (23.9) |
< 0.001 |
| Inadequate antibiotic timing | 718 (10.2) | 46 (15.0) | 672 (10.0) | 0.004 |
| Inadequate antibiotic dosage | 37 (0.5) | 19 (6.2) | 18 (0.3) | < 0.001 |
Continues variables are presented as mean ± SD, and categorical variables as n (%).Active labor was defined as cesarean deliveries performed at more than 4 cm dilation. Not per protocol antibiotics indicate error inantibiotics selection, timing, or dosage.
Adherence to prophylactic antibiotic guidelines
Among women without reported beta-lactam allergies, 739 (10.9%) received not per protocol prophylactic antibiotics (drug, dosage or timing), compared to 201 (65.5%) in the allergy-labeled group (p < 0.001, Table 2). Inadequate antibiotic regimens were observed in 92 (1.4%) cases in the non-allergy labeled group and 164 (53.4%) in the allergy-labeled group (p < 0.001, Table 2). The majority of inadequate regiments involved the administration of clindamycin monotherapy, accounting for 144/164 (88%) of cases (Table 2). Errors in timing and dosage were also more frequent in the allergy-labeled group (Table 2).
Risk factors for SSI
In bivariate analysis, factors statistically associated with increased SSI risk included previous CS, preterm birth, CS performed in active labor, early and artificial rupture of membranes, urgent CS, high American Society Anesthesiologists (ASA) score, contaminated wound (due to meconial amniotic fluid), CS duration and beta-lactam allergy (Table 3). Multivariate logistic regression analysis identified beta-lactam allergy as independent risk factor for SSI (aOR 1.68, CI 95% 1.05 to 2.71, p = 0.031, Table 4). Additional risk factors were identified in the multivariate analysis including CS in Active labor (aOR 2.09, CI 95% 1.49 to 2.93, p < 0.001), high ASA score (aOR 2.00, CI 1.42 to 2.82, p < 0.001, contaminated wound (aOR 1.48, CI 95%, 1.03 to 2.13, p = 0.035) and CS duration (aOR 1.01, CI 95% 1.01 to 1.02, p < 0.001). When beta-lactam allergy was replaced by non-per-protocol antibiotics in the multivariable analysis, non-compliance with antibiotic protocols emerged as preventable independent risk factor for SSI with aOR of 1.95 (CI 95% 1.22 to 3.13, p = 0.006). Hosmer and Lemeshow goodness of fit test was 0.65 and 0.43 for the model with beta-lactam allergy and non-per protocol antibiotics as an explanatory variable respectively.
Table 3.
Risk factors associated with SSIs; Univariate analysis
| Variable | Total (N = 7,060) |
SSI (N = 291) |
No SSI (N = 6,769) |
P value |
|---|---|---|---|---|
| Maternal age (years) | 32.7 ± 5.7 | 32.3 ± 5.6 | 32.7 ± 5.7 | 0.321 |
| Parity | 2.1 ± 1.6 | 2.1 ± 1.3 | 2.1 ± 1.6 | 0.974 |
| Previous CS | 3,013 (42.7) | 101 (34.7) | 2,912 (43.0) | 0.005 |
| BMI (kg/m2) | 29.9 ± 5.9 | 29.5 ± 7.5 | 29.9 ± 5.7 | 0.190 |
| Diabetes mellitus | 1,543 (21.9) | 71 (24.4) | 1,472 (21.7) | 0.159 |
| Gestational age at delivery (weeks ± days) | 38.1 ± 2.4 | 37.8 ± 3.0 | 38.1 ± 2.4 | 0.415 |
|
Number of fetuses 1 2 3 |
6,563 (93) 488 (6.9) 9 (0.1) |
267 (91.8) 22 (7.6) 2 (0.7) |
6,296 (93) 466 (6.9) 7 (0.1) |
0.133 |
| Preterm birth | 1,312 (18.6) | 68 (23.4) | 1,244 (18.4) | 0.032 |
| CS in active labor | 2,573 (36.4) | 163 (56.0) | 2,410 (35.6) | < 0.001 |
|
ROM No SROM AROM PPROM PROM |
4,099 (58.1) 1,498 (21.2) 869 (12.3) 104 (1.5) 490 (6.9) |
130 (44.7) 76 (26.1) 59 (20.3) 9 (3.1) 17 (5.8) |
3,969 (58.6) 1,422 (21.0) 810 (12.0) 95 (1.4) 473 (7.0) |
< 0.001 |
|
Duration of ROM 0.1–5.9 h 6.0-11.9 12-17.9 > 18 |
n = 2,954 1,075 (36.4) 766(25.9) 306 (10.4) 807 (27.3) |
n = 160 49 (30.6) 44 (27.5) 18 (11.3) 49 (30.6) |
n = 2,794 1,026 (36.7) 722 (25.8) 288 (10.3) 758 (27.1) |
0.473 |
|
Amniotic fluid character Clear Meconium Bloody |
6,436 (91.2) 548 (7.8) 76 (1.1) |
246 (84.5) 39 (13.4) 6 (2.1) |
6,190 (91.4) 509 (7.5) 70 (1.0) |
< 0.001 |
|
CS indication Elective Urgent |
2,414 4,646 |
61 (20.9) 230 (79.1) |
2,353 (34.8) 4,416 (65.2) |
< 0.001 |
|
Anesthesia Regional General Combined |
6,306 (89.3) 676 (9.6) 78 (1.1) |
271 (93.1) 15 (5.2) 5 (1.7) |
6,035 (89.2) 661 (9.8) 73 (1.1) |
0.021 |
|
Asa score 1-2 3-5 |
6,473 (91.7) 587 (8.3) |
246 (84.5) 45 (15.5) |
6,227 (92.0) 542 (8.0) |
< 0.001 |
|
Wound class Clean-contaminated Contaminated |
6,505 (92.1) 555 (7.9) |
249 (85.6) 42 (14.4) |
6,256 (88.6) 513 (7.6) |
< 0.001 |
| CS duration (min) | 49.7 ± 20.2 | 56.8 ± 23.7 | 49.4 ± 19.9 | < 0.001 |
|
Beta-lactam allergy Mild Severe |
307 (4.3) 255 (3.6) 52 (0.7) |
20 (6.9) 15 (5.2) 5 (1.7) |
287 (4.2) 240 (3.5) 47 (0.7) |
0.031 0.098 |
| Not per-protocol antibiotic administration | 940 (13.3) | 60 (20.6) | 880 (13.0) | < 0.001 |
| Inadequate antibiotic regimen | 256 (3.6) | 21 (7.2) | 235 (3.5) | < 0.001 |
| Inadequate antibiotic timing | 718 (10.2) | 42 (14.4) | 676 (10.0) | 0.014 |
| Inadequate antibiotic dosage | 37 (0.5) | 4 (1.4) | 33 (0.5) | 0.064 |
Continues variables are presented as mean ± SD, and categorical variables as n (%). Diabetes mellitus- included gestational and pre-gestational diabetes mellitus; Preterm birth- delivery prior to 37 weeks; Active labor was defined as CS performed at more than 4 cm dilation,
CS, Cesarean section; BMI, body mass index; ROM, rupture of membranes; SROM, spontaneous ROM; AROM, artificial ROM; PROM, pre-labor ROM; PPROM, premature PROM prior to 37 weeks of gestation; ASA, American society anesthesiologists
Table 4.
Risk factors associated with SSIs; Multivariate analysis
| Variable | Odds ratio | 95% Confidence interval | P value |
|---|---|---|---|
| Maternal age (years) | 0.998 | 0.976–1.019 | 0.821 |
| Previous CS | 0.976 | 0.734–1.2980 | 0.868 |
| Preterm birth | 1.487 | 1.093–2.024 | 0.012 |
| CS in active labor | 2.090 | 1.490–2.932 | < 0.001 |
|
ROM No SROM AROM PROM PPROM |
1.008 | 0.906–1.1220 | 0.883 |
|
CS indication Elective Urgent |
1.024 | 0.704–1.489 | 0.902 |
|
Asa score 1-2 3-5 |
2.002 | 1.420–2.822 | < 0.001 |
|
Anesthesia Regional General Combined |
0.715 | 0.488–1.047 | 0.085 |
|
Wound class (%) Clean-contaminated Contaminated |
1.480 | 1.027–2.133 | 0.035 |
| CS duration (min) | 1.010 | 1.006–1.015 | < 0.001 |
| Beta-lactam allergy | 1.686 | 1.048–2.714 | 0.031 |
| Inadequate antibiotic timing | 0.911 | 0.639–1.299 | 0.607 |
Continues variables are presented as mean ± SD, and categorical variables as n (%). Diabetes mellitus- included gestational and pre-gestational diabetes mellitus; Preterm birth- delivery prior to 37 weeks; Active labor was defined as CS performed at more than 4 cm dilation,
CS, Cesarean section; ROM, rupture of membranes; SROM, spontaneous ROM, AROM, artificial ROM; PROM, pre-labor ROM; PPROM, premature PROM prior to 37 weeks of gestation; ASA, American society anesthesiologists
Discussion
This study investigated the impact of reported beta-lactam allergy labels on SSIs rates among women undergoing CS. The results demonstrated that women with such labels had an increased risk of SSI, primarily mediated by the administration of non-protocol-compliant antibiotics. These findings underscore that a cefazolin-based prophylactic regimen remains the optimal choice, associated with the lowest SSI rate (3.9% vs. 6.3% with clindamycin plus gentamycin and 8.2% with non-per-protocol regimens).
Since cefazolin and penicillins are structurally distinct antibiotics with different side chain attached to the beta-lactam ring, the American Academy of Allergy, Asthma, and Immunology (AAAAI) guidelines support the use of cefazolin in most patients with a penicillin allergy [6]. Our study demonstrates that in real-world practice, clinicians continue to avoid cefazolin in these patients, opting for substitutes instead of reassessing or challenging the reported allergy, and that such decisions are associated with higher SSI rates. The fact that most self-reported beta-lactam allergy labels are inaccurate [1, 2] with true allergies confirmed in only a small fraction of cases, further questions the justification for routine use of second-line agents. Moreover, emerging resistance to clindamycin among Staphylococci [24] and Streptococci [25, 26] species amplifies the clinical risk linked to these substitutions. Importantly, allergy labels remain essential tools for patient safety and should not be removed indiscriminately. Rather, our findings highlight the need for structured, risk-stratified allergy evaluation and evidence-based perioperative antimicrobial stewardship to ensure that patients receive the most appropriate prophylactic regimen while avoiding preventable adverse reactions.
Previous studies have consistently shown higher rates of SSIs among patients with beta-lactam allergy labels [5, 27, 28]. However, few have examined this specifically in CSs [29–32]. Because antibiotic prophylaxis is universal in this population, our cohort provided a natural control for treatment indication, minimizing selection bias and enabling clearer assessment of the allergy label’s impact on outcomes. In retrospective studies, antibiotic choice is often influenced by patient characteristics, complicating causal inference. In our study, all cesarean patients received prophylaxis regardless of clinical status, and this uniformity served as an instrumental controlled variable [33].
The results revealed that 65% of patients with reported beta-lactam allergies experienced non-adherence to antibiotic guidelines, with 53% receiving an inappropriate antibiotics agent. In most cases, these patients were administered clindamycin alone, which lacked adequate gram-negative coverage. The growing resistance to clindamycin further exacerbates the problem, highlighting the risks associated with its improper use. These findings indicate that beta-lactam allergy labels are a significant source of errors in antibiotic selection and are thus indirectly a clear risk factor for SSIs. In a multivariable analysis, beta-lactam allergy was identified as a significant risk factor for SSI, with an adjusted odds ratio of 1.68 (95% CI 1.048–2.714, p = 0.031), alongside other well-known risk factors such as CS during active labor, high ASA score, contaminated wounds and CS duration. This finding is consistent with those reported by Lam et al. [5] ,Johnston et al. [30] and Harris et al. [32]. Since the impact of beta-lactam allergy on SSIs rates is largely attributed to the use of not per-protocol antibiotics, when a parallel analysis was conducted using inappropriate antibiotic administration as a risk factor instead of beta-lactam allergy, the odds ratio was 1.95 (95% CI 1.217–3.128, p = 0.006), highlighting the combined effect of beta-lactam allergy and other causes of incorrect antibiotic prescriptions.
Our findings highlight the importance of optimizing perioperative antibiotic selection in the setting of reported beta-lactam allergy labels. Both inaccurately documented allergies and overly cautious avoidance of cefazolin may contribute to unnecessary use of second-line or partial regimens. Contemporary evidence indicates that cefazolin can be safely administered to most patients with penicillin allergy, including many with confirmed reactions, due to minimal cross-reactivity and its distinct side-chain structure. Improving allergy assessment and stewardship practices may help ensure appropriate prophylaxis and reduce the risk of surgical site infection.
In our cohort, the rate of patients reporting beta-lactam allergy was significantly lower (4.3%) compared to the commonly reported rate of approximately 10% among hospitalized patients [1, 2]. We hypothesize that this lower rate may be attributable to undocumented cases, potentially resulting from data collection inaccuracies or lapses in reporting by the care teams. Additionally, heightened awareness among our clinical teams regarding the importance of accurately assessing allergies may have contributed to these lower rates. Our medical policy encourages physicians to reassess and potentially de-label patients after thoroughly evaluating the reliability of their reported allergies. This proactive approach likely led to a reduced prevalence of reported beta-lactam allergies, as clinicians became more diligent in verifying these labels. Still, our findings indicate that once an allergy label is established, care teams are more prone to errors in antibiotic prescription. This highlights the need for further antibiotic stewardship interventions to address this issue.
Given the higher SSIs rates observed in patients with reported beta-lactam allergies, careful consideration of allergy testing strategies and wrong allergy labeling removal are warranted to optimize outcomes. Efforts to improve adherence to prophylactic guidelines through clinician education, antibiotic stewardship interventions and standardized protocols may mitigate the identified risks associated with antibiotic non-compliance [34, 35]. Importantly, deviations were also observed among patients without documented allergy labels, most commonly due to errors in prophylactic antibiotic timing (Table 2). This underscores the need for ongoing institutional quality improvement across obstetric prophylaxis practices, not only among allergy-labeled patients.
Additionally, for patients with a reported penicillin allergy who do not have a history of severe immediate reactions to cephalosporins, cefazolin remains an effective choice for surgical prophylaxis. In ongoing efforts to reduce SSIs risk factors, clinicians should be aware of the current guidelines and evidence supporting this approach to optimize patient care and minimize the risk of such infections.
Strengths and limitations
Several limitations merit consideration, including the retrospective nature of the study and the single-center design which may limit generalizability to broader populations. However, the study benefits significantly from a large cohort meeting inclusion criterion, providing robust statistical power. This large sample size enhances the study’s reliability and generalizability. Additionally, the classification of beta-lactam allergies relied on patient-reported data, which may introduce recall bias or inaccuracies. Yet, low rates of missing data are crucial in maintaining the integrity and completeness of the study’s analyses. The meticulous data collection and management protocols employed likely contributed to the minimal missing data, ensuring comprehensive and accurate representation of patient characteristics, antibiotic regimens, and surgical outcomes. Another notable strength of the study is its rigorous post-operative surveillance methodology. SSI events were identified in real-time by an infection control specialist. Moreover, to enhance monitoring accuracy, the infection control team conducted proactive outreach to all women who underwent CSs at our medical center post-surgery. This systematic follow-up allowed for thorough verification of SSI occurrences, contributing to a more comprehensive and reliable dataset.
Conclusion
In conclusion, our study highlights the significant impact of reported beta-lactam allergy labels on SSI rates and adherence to antibiotic prophylaxis guidelines among women undergoing CS. These findings underscore the critical need for rigorous antibiotic stewardship and personalized management strategies in allergic patients to enhance surgical outcomes and ensure patient safety. Importantly, for patients with a reported penicillin allergy who do not have a history of severe immediate reactions to cephalosporins, selecting cefazolin is not only a reasonable choice but a crucial one for effective surgical prophylaxis. Its use can significantly reduce the risk of SSI and aligns with current guidelines, making it essential for clinicians to be well-versed in the evidence supporting this approach. Future research should continue to explore innovative methods to reduce SSIs risk, including strategies for improving antibiotic selection and de-labeling incorrect allergy reports.
Acknowledgements
Not applicable.
Author contributions
Conceptualization: HMZ, MC, MK, GSM, PS; Data curation: HMZ; Formal statistical analysis: PS; Statistical analysis review: MC; Supervision: PS; Writing – original draft: HMZ; Writing – review and editing: MC, MK, GSM, PS.
Funding
The authors report no external funding or financial support relevant to this work.
Data availability
The datasets generated and analysed during the study are available from the corresponding author on reasonable request.
Declarations
Ethics approval and consent to participate
The study was approved by the hospital’s local ethics committee (approval number 0197-23MMC). Given the retrospective design and use of de-identified data, the requirement for informed consent was waived, in accordance with the Declaration of Helsinki.
Consent for publications
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets generated and analysed during the study are available from the corresponding author on reasonable request.