Table 1.
General features of the included studies for quantitative synthesis.
| Author, Year [Ref.] | Country, Design and No. Centers |
Study Period |
Main Inclusion and Exclusion Criteria | Type of Infection |
Study Population |
Group | Mortality (Definition) | Safety Assessment (Definition) |
Length of Stay(Definition) | Multivariable Analysis on Mortality (Type and Variables) |
Comments | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Reference Regimen (Number of Patients, Daily Dose, Treatment Duration, Combination Therapy [%]) |
Comparator (Number of Patients, Daily Dose, Treatment Duration, Combination Therapy [%, Drug]) |
Other Comparators (Number of Patients, Daily Dose, Treatment Duration, Combination Therapy [%, Drug]) If Any |
|||||||||||
| Garcia Paez et al., 2008 [21] | Brazil—Retrospective -single center | From July 1999 to July 2005 |
Inclusion: only adult patients. Exclusion: colonization and not infection by SM, medical record unavailable | BSI: 87% Pneumonia: 13% |
Adults Male: 70% Mean age 48.9 years Malignancy: 45% |
Regimen: TMP/SMX (Dosage not specified) Duration undefined |
Regimen: others (Dosage not specified) Duration undefined |
N/A | TMP/SMX: 26% Others: 46% (14-day) |
Not addressed | Not addressed | Not addressed | Absence of therapy excluded from comparator; not clear if TMP/SMX used as monotherapy or not Polymicrobial infection: 30% Non-comparative study |
| Czosnowski et al., 2011 [22] | United States, Retrospective- Single center | January 1997–December 2007 | Inclusion: only adult, ICU. Exclusion: incomplete medical record data. |
VAP | Adults Male: 76% Mean age 40 years Traumatic brain injury: 56% |
Regimen: TMP/SMX (11.2 ± 3.8 mg/kg/day) Duration undefined Combination allowed |
Regimen: Others (Dosage not specified) Duration undefined Combination allowed |
N/A | N/A | Not addressed | Not addressed | Not addressed | Polymicrobial infection: 66% No data on mortality, only on clinical failure Treatment failure defined as either clinical failure, or microbiologic plus clinical failure: TMP/SMX: 14% Others: 8% Overall treatment duration was 11.4 days (mean) Non-comparative study |
| Tekce et al., 2012 [23] | Turkey—Retrospective cohort—Single center | From January 2008 to December 2010 |
Inclusion: Patients who had received more than 3 days of TMP/SMX or tigecycline for nosocomial SM infection |
Pneumonia: 51% SSI: 29% |
Adults. Male: 53% Mean age 65.4 years Malignancy: 29% ICU stay: 87% |
Regimen: TMP/SMX (Dosage not specified) Duration undefined 0% combination |
Regimen: Tigecycline (Dosage not specified) Duration undefined 0% combination |
N/A | TMP/SMX: 31% Tigecycline: 21% (30-day) |
Not addressed | Not addressed | Not reported | Polymicrobial infection: 29 (64.4%) patients Comparative study |
| Cho et al., 2014 [24] | South Korea—Retrospective cohort—Single center | From 2000 to 2012 |
Inclusion: only adult patients. Exclusion: combination therapy between TMP/SMX and levofloxacin, death within the first 2 days after the start of the therapy | BSI | Adults Median age 58 years (IQR 45–67) Malignancy: 52% MV: 16% |
Regimen: TMP/SMX 51-patients (15–20 mg/kg of body weight/day TMP) Duration undefined 18% combination |
Regimen: Levofloxacin—35 patients (750 mg/day) Duration undefined 9% combination |
N/A | TMP/SMX: 27% Levofloxacin: 20% (30-day) |
TMP/SMX: 24% Levofloxacin: 0% (adverse events) |
TMP/SMX: median 25 days (IQR 12–51) FQs: median 27 days (IQR 15–52) (hospital stay) |
Levofloxacin use versus TMP/SMX: aOR 0.62 (95% CI 0.19–2.04) Adjusted was made for septic shock and pneumonia |
Data could be stratified according to monotherapy and combination therapy. Polymicrobial infection: 20% Recurrence (30-day): TMP/SMX = 12% Levofloxacin = 6% Comparative study |
| Wang YL et al., 2014 [25] | United States—Retrospective cohort—Single center | From January 2008 to December 2011 | Adult patients with nosocomial SM infection received monotherapy with TMP/SMX or an FQ for at least 48 h. |
Pulmonary infection: 56% SSTI: 19% UTI: 9% IAI: 9% Secondary BSI: 6% |
Adults Male: 61% Mean age: 73 years Solid organ malignancy: 39% MV: 30% |
Regimen: TMP/SMX 35-patients (Dosage not specified) Median duration 8 days (IQR 2–28) 0% combination |
Regimen: FQs—63 patients Levofloxacin = 76% Ciprofloxacin = 24% (Dosage not specified) Median duration 9 days (IQR 2–8) 0% combination |
N/A | TMP/SMX: 22% FQs: 31% (30-day) |
Not addressed | TMP/SMX: median 16 days (IQR 8–42) FQs: median 25 days (IQR 15–37) (hospital stay) |
Not reported | Polymicrobial infection: 77% ICU admission at time of culture: 24% Comparative study |
| Gokhan Gozel et al., 2015 [26] | Turkey— Retrospective, Single center |
From January 2006 to December 2013 | Inclusion: only adult patients. Exclusion: polymicrobial infection |
BSI: 49% Pneumonia 51% | Adults Male: 66% Median age 68 years (IQR 20–87) Malignancy: 24% |
Regimen: TMP/SMX—26 patients (Dosage not specified) Duration undefined 0% combination |
Regimen: Levofloxacin-31 patients (Dosage not specified) Duration undefined 0% combination |
N/A | TMP/SMX: 31% Levofloxacin: 23% (14-day) |
Not addressed | Not addressed | Not addressed | Unpublished data of the original article were retrieved from the paper of Ko et al. [10] Polymicrobial infection: 11% Non-comparative study |
| Hand et al., 2016 [27] |
United States—Retrospective—Single center | From January 2006 to December 2012 | Inclusion: adult and pediatric patients with; one positive culture for SM. Exclusion: combination therapy, concomitant antibiotics with anti-SM activity other than the ones studied. |
Mixed | Male: 47% Mean age: 52 years (calculated combining two means) MV: 51% |
Regimen: TMP/SMX—22 patients (average daily doses of 200 mg/day SMX and 8.5 mg/kg/day TMP) Median duration 7 days (IQR 3–15) 0% combination |
Regimen: Minocycline-23 patients (200 mg daily) Median duration 14 days (IQR 4–12) 0% combination |
N/A | TMP/SMX: 9% Minocycline: 9% (30-day) |
Not addressed | TMP/SMX: median 54 days (IQR 4–265) Minocycline: median 41 days (IQR 6–136) (hospital stay) |
Not addressed | Polymicrobial infection: 73% Treatment failure (isolation of SM on follow-up culture from the same site as the initial infection within 30 days of the initial culture or in-hospital death within 30 days of the initial positive culture or receipt of an alternative or additional antibiotic possessing in vitro activity against SM during any point of initial therapy): TMP/SMX = 39% Minocycline = 48% Comparative study |
| Wang CH et al., 2016 [28] |
Taiwan—Retrospective—Single center | From January 2004 to December 2013 | Inclusion: All patients with monomicrobial SM BSI. Exclusion: patients who had polymicrobial BSI or who were aged <18 years. |
BSI | Adults Male: 73% Mean age: 68.3 years Malignancy: 38% MV: 64% |
Regimen: TMP/SMX—64 patients (Dosage not specified) Duration undefined 0% combination |
Regimen: FQs—23 patients (Dosage not specified) Duration undefined 0% combination |
N/A | TMP/SMX: 59% FQs: 9% (in-hospital) |
Not addressed | Not addressed | Not addressed | Unpublished data of the original article were retrieved from the paper of Ko et al. [10] Non-comparative study |
| Chen et al., 2017 [29] |
China—Retrospective cohort—Single center | From January 2009 to March 2015 | Inclusion: only adult patients. Exclusion: patients without adequate medical records or any clinical manifestation. |
BSI | Adults Male: 64% Solid tumors: 26% ICU: 26% |
Monotherapy—51 patients (Dosage not specified) Duration undefined |
Combination therapy—27 patients (Dosage not specified) Duration undefined |
N/A | Monotherapy: 25% Combination therapy: 26% (30-day) |
Not addressed | Not addressed | Not addressed | In two-thirds of cases combo based on levofloxacin Non-comparative study |
| Ebara et al., 2017 [30] | South Korea—Retrospective cohort—Multicenter | From January 2007 to December 2013 | Inclusion: Adults and pediatrics with SM BSI | BSI | Adults Male: 64% |
Regimen: FQs—15 patients (Dosage not specified) Duration undefined 0% combination |
Regimen: Minocycline—10 patients (Dosage not specified) Duration undefined 0% combination |
N/A | FQs: 53% Minocycline: 40% (90-day) |
Not addressed | Not addressed | Not addressed | Unpublished data of the original article were retrieved from the paper of Ko et al. [10] Non-comparative study |
| Kim SH et al., 2018 [31] | South Korea—Retrospective cohort—Single center | From January 2006 to December 2016 | Inclusion: Adults, cancer patients; Exclusion: combination therapy |
BSI | Adults Male: 59% Mean age: 55.7 years |
Regimen: TMP/SMX—31 patients (Dosage not specified) Duration undefined 0% combination |
Regimen: Levofloxacin—40 patients (Dosage not specified) Duration undefined 0% combination |
N/A | TMP/SMX: 43% Levofloxacin: 36% (30-day) |
Not addressed | Not addressed | Not addressed | Case-control study (controls being not-SM BSI) Non-comparative study |
| Velázquez-Acosta et al., 2018 [32] | Mexico—Retrospective cohort—Single center | From January 2000 to December 2016 | Adult patients with BSI or pneumonia by SM | BSI: 55% Pneumonia: 45 |
Adults Male: 42% Mean age: 46.9 years Solid tumors: 63% Hematologic malignancies: 37% |
Regimen: TMP/SMX—87 patients (Dosage not specified) Duration undefined 22% combination |
Regimen: FQs—39 patients (Dosage not specified) Duration undefined Combination allowed |
Regimen: Other—84 patients Not reported |
TMP/SMX: 44% FQs: 18% Other: 24% (30-day) |
Not addressed | Not addressed | No TMP/SMX use versus its use: aOR 0.87 (95% CI 0.3–2.65) Adjusting was made for age and appropriateness of therapy |
Polymicrobial bacteremia: 20% (out of 95 BSI) All study population was composed of oncologic/ onco-hematologic patients Non-comparative study |
| Watson et al., 2018 [33] | United States—Retrospective cohort—Single center | From January 2004 to October 2014 | Inclusion: patients at least 18 years of age that received at least 48 h of monotherapy with FQ or TMP/SMX. Exclusion: combination active therapy or therapy for less than 48 h. |
BSI | Adults Male: 48% Mean age: 51.4 years (calculated combining two means) MV: 33% |
Regimen: TMP/SMX—32 patients (Dosage not specified) Duration undefined 0% combination |
Regimen: FQs—22 patients (Dosage not specified) Duration undefined 0% combination |
N/A | TMP/SMX: 31% FQs: 14% (in-hospital) |
TMP/SMX: 6% FQs: 5% (drug discontinuation) |
TMP/SMX: 15 (IQR 7–38) days Levofloxacin:9 (IQR 5–16) days (hospital LOS) |
Not addressed | Comparative study |
| Kim EJ, 2019 [34] | South Korea—Retrospective cohort—Multicenter | From January 2006 to December 2014 | Inclusion: patients at least 18 years of age and positive blood culture for SM |
BSI | Adults Solid tumor: 40% Hematological malignancy: 14 |
Regimen: TMP/SMX—31 patients (Dosage not specified) Duration undefined Combination allowed |
Regimen: FQs—40 patients (Dosage not specified) Duration undefined Combination allowed |
N/A | TMP/SMX: 87% FQs: 48% (60-day) |
Not addressed | Not addressed | Not addressed | Non-comparative study |
| Nys et al., 2019 [35] | United States—Retrospective cohort—Single center | From January 2012 to October 2016 | Inclusion: Adults Exclusion: polymicrobial infections. |
Lung infection: 92% UTI: 3%. |
Adults Male: 54% Median age: 63 (IQR 51–70) years MV: 37% |
Regimen: TMP/SMX—45 patients (median dose 10.3 mg/kg/day) Median duration 13 days (IQR 8-15) 0% combination |
Regimen: Levofloxacin—31 patients (median dose 750 mg/day) Median duration 13 days (8–15) 0% combination |
N/A | TMP/SMX: 16% Levofloxacin: 13% (28-day) |
TMP/SMX: 7% Levofloxacin: 0% (Adverse events) |
Not addressed | Not addressed | Clinical cure (at the end of therapy): TMP/SMX = 82% Levofloxacin = 74% Comparative study |
| Shah et al., 2019 [36] | United States—Retrospective cohort | From November 2011 to October 2017 |
Patients with SM pneumonia. Exclusion: Less than 48 h of effective therapy. |
Pneumonia | Adults Mean age 62 years (derived from combining group) Male: 62% Immunocompromised: 20% Polymicrobial pneumonia: 54% |
Regimen: Monotherapy—214 patients TMP/SMX= 66% FQs = 30% Other = 4% (Dosage not specified) Duration undefined |
Regimen: Combination therapy—38 patients TMP/STX + FQ = 50% TMP/STX + minocycline = 16% FQs + minocycline = 13% Duration undefined (Dosage not specified) |
Not reported | Monotherapy: 23% Combination therapy: 40%% (30-day) |
Not addressed | Monotherapy: 22 (IQR 14–35) days Combination therapy: 22.5 (IQR 14–44) days (hospital LOS) |
Not addressed | Recurrence (30-day): Monotherapy = 8% Combination therapy = 11% Clinical cure (Improvement in signs and symptoms of infection after 7 days of effective therapy): Monotherapy = 60% Combination therapy = 53% Comparative study |
| Tokatly Latzer et al., 2019 [37] | Israel—Retrospective cohort—Multicenter | From 2012 to 2017 | Patients hospitalized in pediatric ICU affected by BSI related to SM with or without a culture from a commonly sterile respiratory site |
BSI: 42% CVC-related BSI: 22% BSI + Pleural fluid: 22% |
Children younger than 18 years old. Oncologic: 22% Cerebral palsy: 22% Congenital cardiac disease: 15% Immunodeficiency: 9% End-stage renal disease: 7% Burss: 4% |
Regimen: TMP/SMX—22 patients (Dosage not specified) Duration undefined Combination allowed |
Regimen: Ciprofloxacin—13 patients (Dosage not specified) Duration undefined Combination allowed |
Regimens Ciprofloxacin + TMP/SMX Ciprofloxacin + TMP/SMX + Minocycline Ceftazidime (Dosage not specified) Duration undefined Combination allowed |
TMP/SMX: 27% Ciprofloxacin: 21% Ciprofloxacin + TMP/SMX: 10% Ciprofloxacin + TMP/SMX + Minocycline: 17% Ceftazidime: 14% (7-day) |
Not addressed | Not addressed | Not addressed | Polymicrobial infection 37 (55%) When considering only monotherapy, just 35 cases were taken into account Non-comparative study |
| Alsuhaibani et al., 2021 [38] | Saudi Arabia,—Retrospective cohort—Single center | From January 2007 to December 2018 | Inclusion: Pediatrics patients; Exclusion: asymptomatic patients, no therapy | BSI | Pediatrics. Male: 50% Under 12 months: 38% Malignancy: 29% Polymicrobial infection 30.9% |
Regimen: TMP/SMX—36 patients (Dosage not specified) Duration undefined 0% combination |
Regimen: TMP/SMX + others—11 patients (Dosage not specified) Duration undefined 100% combination |
N/A | TMP/SMX: 31% TMP/SMX + others: 36% (7-day) |
Not addressed | Not addressed | Not addressed | Comparative study (monotherapy versus combination therapy) |
| Junco et al., 2021 [39] |
United States—Retrospective cohort—Multicenter | From January 2010 to January 2016 | Inclusion: Adults; Exclusion: combination therapy, less than 48 h of monotherapy, patients with diagnosis of cystic fibrosis, resistance to initial therapy; SM infection in the previous 12 months |
Pneumonia: 68%; BSI: 10%; UTI: 9%; ABSSSI: 11%; Other infections: 2%. |
Adults Male: 61% Mean age: 59.6 years MV: 56% |
Regimen: TMP/SMX—217 patients (median dose 9.7 mg/kg/day) Median duration 12 days 0% combination |
Regimen: FQs—28 patients (Ciprofloxacin 800 mg/day or levofloxacin 750 mg/daily or moxifloxacin 400 mg/day) Median duration 12 days 0% combination |
Regimen: Minocycline—39 patients (200 mg/day) Median duration 12 days 0% combination |
TMP/SMX: 15% FQs: 29% Minocycline: 5% (30-day) |
TMP/SMX: 47% FQs: 75% Minocycline: 74% (KDIGO AKI stage 1-2-3) |
Median values TMP/SMX: 12 days (IQR 8–17) FQs: 12.5 days (IQR 8–19) Minocycline: 14 days (IQR 11–18) (infection-related LOS) |
FQ use: aOR 0.3 (95% CI 0.1–2.1)— Adjusted for vasopressor support, APACHE, age, LOS prior to culture—FQ versus TMP/SMX Minocycline use: aOR 0.2 (95% CI 0.1–0–7)— Adjusted for vasopressor support, APACHE, age, LOS prior to culture-minocycline versus TMP/SMX) |
Polymicrobial infection included but not specificied Clinical failure (isolation of SM from a subsequently collected culture from the same site of index culture after at least 48 h of therapy or alteration of monotherapy after at least 48 h of treatment for either an adverse event or concern for clinical failure or 30-day in-hospital all-cause mortality): TMP/SMX = 35% FQs = 29% Minocycline = 39% Comparative study (for the meta-analysis the “others” group comprised FQs plus TDs) |
| Puech et al., 2021 [40] | Reunion Island (French overseas department)—Retrospective cohort—Single center | From January 2010 to December 2018 | Patients ICU-admitted with VAP by SM |
100% VAP | Adults Male: 64% Median age: 61 [IQR 51–70] years Median SOFA: 9 [IQR 7–12] Immunoompromised: 5%; BSI: 3% Polymicrobial 58% |
Regimen: TMP/SMX—80 patients (1200 mg/240 mg each 6 h) Duration undefined Combination allowed |
Regimen: FQs—84 patients (ciprofloxacin 400 mg/8 h or moxifloxacin 400 mg/day) Duration undefined Combination allowed |
Regimen (Other)—132 patients: Ticarcillin/ clavulanate 4 g/8 h; or ceftazidime 2 g/6 h Duration undefined Combination allowed |
TMP/SMX: 50% FQs: 52% Ticarcillin/ clavulanate: 79% Ceftazidime 56% (in-hospital) |
Not addressed | Not addressed | Not addressed | Monomicrobial infections in 55% cases. Monotherapy only in 4 patients (0.03%) Median MV duration: 21 [IQR 14–37] days Non-comparative study |
| Tuncel et al., 2021 [41] | Turkey—Retrospective cohort—Single center | From January 2002 to December 2016 | Adult patients with nosocomial SM BSI | Catheter-related BSI: 21% Pneumonia: 7% Intraabdominal Infection: 6% Undetected source: 67% |
Median (IQR) age: 54 (18–84) years Male: 58% ICU: 51%; Inpatient clinic: 49% Solid organ malignancy 30%.; Hematological malignancy 23%; Cerebrovascular disease: 17%; Multiple underlying diseases: 31% |
Regimen: TMP/SMX—49 patients Duration undefined (Dosage not specified) Combination allowed |
Regimen: Levofloxacin—17 patients Duration undefined (Dosage not specified) Combination allowed |
Regimen: Other—28 patients |
14-day mortality TMP/SMX: 22% Levofloxacin: 24% Other: 36% 30-day mortality TMP/SMX: 37% Levofloxacin: 24% Other: 55% |
Not addressed | Not addressed | Not addressed | Polymicrobial infections: 34% Exclusion of 38 patients under TMP/SMX plus levofloxacin Non-comparative study |
| Zha et al., 2021 [42] | China—Retrospective cohort—Multicenter | From January 2017 to December 2020 | Adult patients ICU-admitted with VAP by SM |
100% VAP | Median (IQR) age = 76 (64.25–85) years Male: 79% Median APACHE II Score: 21 (IQR 16.25–24) Median Charlson index comorbidity score: 5 (IQR 4–6) Malignancy: 10 (12.2%) |
Regimen: FQs—36 patients (dosage Levofloxacin 750 mg/daily; Moxifloxacin 400 mg/daily) 0% combination |
Regimen: Tigecycline—46 patients (dosage: 100 mg followed by 50 mg × 2/daily) 0% combination |
N/A | FQs: 28% Tigecycline: 48% (28-day) |
Not addressed | Not addressed | Tigecycline versus FQs: aOR 1.64 (95% CI 0.58–4.77) Adjusting was made for the following variable: age, gender, chronic kidney disease, coagulation disorder, malignancy, polymicrobial infection, definitive antibiotic therapy, combination therapy with carbapenems, APACHE II score and Charlson comorbidity index score |
Polymicrobial infections: 71% A. baumannii: 45% P. aeruginosa: 17% Clinical cure (complete resolution of all signs and symptoms of pneumonia at 14 days after the initial given dose of target antibiotics): FQs = 64% Tigecycline = 33% Comparative study |
| Ahlstrom et al., 2022 [43] | Denmark—Retrospective cohort—Single center | From January 2015 to June 2020 | Patients with positive blood culture with detectable SM | 100% BSI | Mainly adult patients with median age 41 (IQR 16–67) Male: 64% ICU: 23% |
Regimen: TMP/SMX—48 patients (Dosage not specified) Duration undefined Combination allowed |
Regimen: Ciprofloxacin —22 patients Duration undefined Combination allowed |
N/A | TMP/SMX: 19% FQs: 18% (90-day) |
Not addressed | Not addressed | TMP/SMX use: Adjusted HR 0.76 (95% CI 0.23–2.54) | 14/48 of TMP/SMX patients received ciprofloxacin, 14/22 viceversa Non-comparative study |
| Sarzynski et al., 2022 [44] | United States—Retrospective cohort—Multicenter | From January 2005 to December 2017 |
Adult patients with BSI or LRTI by SM infection Exclusion: Inconsistent/no therapy |
TMP/SMX: BSI = 8,4%; LRTI = 91.6% FQs: BSI = 12%; LRTI = 88% |
Adults Male: 57% TMP-SMX median age: 60 [IQR, 31–72] years MV: 38.7% ICU stay: 33.5% Immunocompromised: 1% Levofloxacin: age 66 [IQR, 53–76] years MV: 31.2% ICU stay: 28.8% Immunocompromised: 1.7% |
Regimen: TMP/SMX—758 patients (Dosage not specified) Duration undefined 0% combination |
Regimen: Levofloxacin—823 patients (Dosage not specified) Duration undefined 0% combination |
N/A | In-hospital: TMP/SMX =14.2% Levofloxacin = 10.6% Total mortality: TMP/SMX =17.7% Levofloxacin = 15.2% |
Not addressed | TMP/SMX: 17 (9–31.8) days Levofloxacin:10 (5–21) days (hospital LOS) |
FQs versus TMP/SMX: aOR 0.76 (95% CI 0.58–1.00). Adjusted values were computed using logistic regression after controlling for baseline patient and hospital level factors. |
Polymicrobial infection: Levofloxacin = 42%, TMP/SMX = 42% Comparative study |
Abbreviations: ABSSSI: Acute Bacterial Skin and Skin Structure Infection; AKI: cute kidney injury; aOR: adjusted odds ratio; BSI: bloodstream infection; CI: confidence interval; FQs = fluoroquinolones; HR: hazard ratio; ICU: intensive care unit; IQR: interquartile range; KDIGO: Kidney Disease: Improving Global Outcomes; IAI: intra-abdominal infection; LOS: length of stay; LRTI: lower respiratory tract infection; MV = mechanical ventilation; N/A: not applicable; OR: odds ratio; SM: Stenotrophomonas maltophilia; SSTI: skin and soft tissue infection; TMP/SMX = trimethoprim/sulfamethoxazole; UTI; urinary tract infection; VAP: ventilator-associated pneumonia.