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A Systematic Review of the Peer-Reviewed Literature on Personalized Phage Therapy

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16 June 2026

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17 June 2026

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Abstract
The increase in antimicrobial resistant infections has fueled a resurgent interest in bacteriophage (phage) therapy. We conducted a systematic review of personalized phage therapy cases in the peer-reviewed, English-language literature reported between 1/1/2005, to 8/31/2025 for which individual patient data were available, for a total of 323 patients in 83 studies. Most patients (68%, 221/323) were treated with ≥2 phages (a phage cocktail). The median concentrations of phages was 108 PFU/mL (IQR 107-109). Most patients (76%, 246/323) received antibiotics concurrent with phage therapy. The median duration of therapy was 10 days (IQR 5-21). The most common indications for phage therapy were skin/soft tissue, pulmonary, orthopedic, osteoarticular, and genitourinary infections. 144 patients received fixed (off-the shelf) phage preparations whereas 179 received bespoke phage preparations in which all of these were screened for in vitro efficacy against the patient’s clinical isolates prior to treatment initiation (e.g. personalized therapy). For cases where outcomes data were available, 78% (253/323), experienced clinical improvement while the targeted pathogen was eradicated in 61% (177/290) of cases. Nine patients had treatment withdrawn due to tolerability concerns. These data indicate that there is substantial heterogeneity in current personalized phage therapy clinical practices but that this approach can be successful.
Keywords: 
bacteriophage
;  
therapy
;  
systematic review
;  
bacteriophage therapy
;  
antimicrobial resistance
;  
phage therapy
;  
antibiotic resistance
;  
case report
;  
compassionate use
Subject: 
Medicine and Pharmacology  -   Epidemiology and Infectious Diseases

1. Introduction

Antimicrobial resistance (AMR) to antibiotics is a growing critical threat to global health outcomes, requiring new therapeutic approaches. Lytic bacteriophages (phages), viruses that kill bacteria, are a promising therapeutic approach in the fight against AMR infections [1,2,3,4]. In the past, phage therapy was largely sidelined in Western Europe and North America in favor of small molecule antibiotics [5,6]. However, as conventional antibiotics become increasingly ineffective against resistant infections, Western researchers have begun to reexamine phage therapy as a possible therapeutic modality [7,8].
Currently, most phage therapy is implemented in a personalized manner, where phages are matched to a patient’s particular bacterial pathogen [9,10]. Personalized phage preparations are either bespoke, that is to say, isolated anew or selected from a library, or matched to a pre-established set of fixed phages [11]. The phages used in these cases are typically unique to each facility. There also remains substantial variation in phage production and quality control practices, though evidence-based protocols are starting to emerge [12,13]. Non-personalized, off-the shelf phage therapy is also used, typically in the context of randomized clinical trials (RCT). Most RCTs conducted to date have largely failed to demonstrate efficacy, although there are several recent studies reporting promising results [14,15,16]. Nonetheless, at present most phage therapy cases involved personalized regimens.
There are some areas of emerging consensus around phage therapy practices [17]. For example, multiple phages are typically administered simultaneous as a “cocktail” to limit the emergence of bacterial resistance to phage; however, the number of phages in cocktails can vary [18,19,20,21]. Phages are also usually administered together with small molecule antibiotics which are given as standard of care [22,23].
However, there is also substantial heterogeneity in the phage administration protocols, including in regards to the dose, route, frequency, and duration of phage therapy [24,25,26]. Moreover, most clinical data published in the medical literature from personalized phage therapy are from case reports, case series, or small uncontrolled studies, making the optimal practices unclear [27]. There are several systematic reviews that have interpreted this literature [26,28,29,30]. However, there has been rapid growth in the number of published cases such that an updated assessment is warranted. Moreover, those studies are typically not limited to personalized phage therapy cases.
Here, we have performed a systematic review of personalized phage therapy cases reported in the peer-reviewed, English-language literature between January 1, 2005, to August 31, 2025. By focusing on reports where individual patient data is available, we hope to gain both an understanding of current practices as well as to facilitate an appreciation of best practices in personalized phage therapy.

2. Materials and Methods

2.1. Electronic Search

Two investigators (PMB and GC) independently completed literature searches using the Medline database (PubMed) from January 1, 2005, to August 31, 2025. The search terms, “phage”, “phages”, “bacteriophage”, and “treatment”, “administration,” “intervention”, or “therapy” were used with the filters for “case reports”, “clinical trial”, “randomized controlled trial” were used. A list of potentially eligible studies was compiled from this list using the 2020 Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) recommendations.

2.2. Inclusion/Exclusion

We sought to include studies with consistent patient data to conduct our review. Studies were included if they met the following criteria: (1) published in a peer-reviewed English-language journal between January 1, 2005 and August 31, 2025, (2) phage therapy was administered in human subjects for the purpose of treating a bacterial infection, (3) individual patient data reported included (a) phage concentration or titer of administered dose, (b) frequency and duration of phage therapy, (c) clinical outcome posttreatment, and (d) safety data. Studies that did not meet these criteria were excluded from our report. Some studies included patients that had previously been described in multiple case reports. Here, the first published study was included and the patient listed in subsequent reports were omitted so as not to duplicate patient cases. If the case series provided new or missing information to the individual case report, this was included and referenced. Due to this strict individual patient data inclusion criteria, many clinical trials lacking this information were excluded.

2.3. Data Extraction

The following information was extracted from the studies and compiled into a database: author, year, article PMID, patient sex and age, patient history, type of infection, hardware infection (yes/no), species of the targeted pathogens, whether surgery was concurrent (yes/no), number of and administration route(s), frequency and duration of phage administration, whether phages were ‘off the shelf’, number of phage types, phage treatment log, in vitro phage susceptibility testing (yes/no; this was considered to be positive if at least one phage had lytic plaque activity against at least one of the target pathogens), use of concurrent anti-infectives (yes/no), host bacteria eradication (yes/no), clinical efficacy defined as perceived clinical improvement and/or resolution of the infection attributed to phage therapy, patient survival, and adverse effects attributed to phage therapy. When multiple sites of infection were involved, typically the primary site of infection was used for disease categorization. When multiple phage concentrations were administered, the highest concentration reported was documented. When multiple frequencies of administration were reported and multiple modalities were used, the most common frequency of administration was recorded. Duration was calculated as the total number of days, consecutive and non-consecutive, phage administered.
Lastly, we examined site(s) of infection and pathogen for each patient, as well as whether therapy was given with surgical revision surgery. We categorized patient outcomes by whether the infection was eradicated, or if the patient substantially improved over a 1+ month period, and presence of suspected adverse effects.
Summary statistics were performed to assess each treatment modality. Due to the heterogeneity of the treatment protocols, phage preparations, and treatment centers, no further statistical analysis could be performed.

3. Results

3.1. Literature Search

A total of 263 articles were obtained from two independent searches done by two investigators (PB and GC). Eighty-three studies and eighty-five reports met criteria for inclusion (Figure 1). Note, two articles or studies published data on the same case, hence the distinction of 83 studies and 85 reports. These two reports included additional information on previously described patients. The information was merged to provide a more accurate clinical picture, references of the included studies were manually searched for additional relevant publications. Major case reports and clinical trials not found in our literature search were included [9,14,31,32]. From these articles, 323 individual patient cases were identified after duplicates from multiple reports removed.

3.2. Patient Characteristics

A total of 323 patients who received personalized phage therapy were included in this study. Sex was reported for 156 patients; 55% were males (85/156). Age was reported in ranges for 219 patients, with exact age being disclosed for 119 patients with a median age of 52 (IQR 35-68, minimum 1, maximum 96). The age and gender of patients is shown in Figure 2.

3.3. Indications

The most common pathogens involved in phage therapy in this dataset were Staphylococcus aureus and Pseudomonas aeruginosa. Smaller numbers of patients were treated for other Staphylococcus spp, Klebsiella pneumoniae, Acinetobacter baumannii, and other pathogens (Figure 3).
Patients were treated with phage therapy for the following indications: skin and soft tissue infections (56/323), pulmonary infections (54/323), orthopedic hardware infections (53/323), osteoarticular infections (40/323), genitourinary infection (32/323), upper respiratory tract infections (29/323), cardiac hardware infections (26/323), otitis infections (14/323), abdominal infections (8/323), native infective endocarditis (5/323), sepsis (3/323), other hardware infections (2/323), and one central nervous system infections.

3.4. Regimens

Most patients (68%, 221/323) were treated with 2 or more phages, (i.e. a “cocktail” of phages) while 32% (102/323) were treated with a single phage. The median concentration was 108 (IQR 107-109). Most patients (76%, 246/323) received antibiotics concurrently with phage therapy.
Phage therapy was administered in a variety of routes, with the most common being intravenous, intraoperative, and topical (Figure 4). Local routes of administration were defined as phages delivered to a specific non-cutaneous, non-mucosal anatomical site to achieve a localized effect, whereas topical administration was defined specifically as application of phage to skin surface. Intranasal was defined as delivery through the nasal cavity without aerosolization, while nebulized phage was defined as aerosolized phage delivered through the nasal or oral cavity. Most patients received phage by only one route (195/323, 60%), with a median of 1 (IQR 1-2) route of delivery.
Patients received phage therapy in varying frequencies. The mean cumulative duration of therapy was 24 days (1-1492), median duration was 10 days (IQR 5-21). For the subset of 290 cases where outcomes data were available, bacterial eradication rates were 57% (106/186) for one route vs 68% (71/104) for multiple routes of administration.

3.5. Safety of Phage Therapy

Phage therapy was generally well-tolerated. Overall, 10% (31/323) of patients experienced adverse events possibly or probably related to phage therapy. These adverse events, some of which occurred in the same patient, included 9 fevers, 7 transient tachycardic events, 7 afebrile chills, 9 transaminitis events, 2 instances of local pain, 2 instances of leukopenia, and one instance of wheezing, vasopressor dependency, shortness of breath, lip rash, local redness, fatigue, dizziness, cytokine storm, coughing, and abdominal discomfort. (Figure 5).

3.5.1. Phage Therapy Efficacy

Phage therapy efficacy was assessed by reports of clinical improvement or cure as well as bacterial eradication. Most patients, 78% (253/323), experienced clinical improvement or cure following phage therapy. Phage therapy eradicated the targeted pathogen in 61% (177/290) of cases whereas 39% (113/290) of patients had persistent bacterial infection despite phage therapy. Pathogen eradication was unknown in 6% (24/323) of total cases and 9 patients had their therapy withdrawn due to transient tachycardia and chills in the singular study’s other participants (Figure 6).

3.5.2. Skin and Soft Tissue Infections

A total of 56 patients across 8 studies [9,31,33,34,35,36,37,38,39] were treated for difficult-to-treat soft tissue infections with phage. Common indications were chronic non-healing ulcers (n=21), diabetic foot infections with amputation risk (n=10), infection secondary to burns (n=9), and infection secondary to surgical wounds (n=5), among other indications (Table 1). The pathogens involved in these cases included S. aureus (n=30), P. aeruginosa (n=22), E. coli (n=6), S. hominis, S. maltophilia, Streptococcus spp., and A. baumanii (n=1 each).
Patients with these infections were given phage therapy primarily via topical administration (n=44), but also through IV (n=7), orally (n=4), locally (n=4), intraoperatively (n=4), nebulized (n=2), and via catheter (n=1).
The median titer of administered phage was 109 PFU/mL (IQR 107-109 PFU/mL) given at frequency of every 8 hours to every 48 hours. Four interventions were one-time administrations. Excluding one-time administrations, the median treatment duration was 7 days (IQR 5-14). A total of 30 patients had phage therapy concurrent with antibiotic therapy.
Out of 56 patients, 84% experienced clinical recovery (47/56). 61% showed total eradication of pathogen (35/56). One patient experienced fever with dubious links to therapy [34]. No other adverse events were attributed to phage therapy.

3.5.3. Pulmonary Infections

A total of 54 patients across 23 studies [9,38,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60] were given therapy for difficult-to-treat pulmonary infections with phage therapy. The treated indications were cystic fibrosis related complications (n=14), COVID-19 related complications (n=8), surgical related infections (n=7), and COPD (n=4) (Table 2). The pathogens involved in these cases included P. aeruginosa (n=31), A. baumanii (n=6), A. xylosoxidans (n=5), M. abscessus (n=5), K. pneumoniae (n=3), S. aureus (n=2), and 1 patient each for B. dolosa, B. multivorans, S. marcescens, and S. maltophilia.
Patients with these infections were given therapy primarily via nebulizer (n=46), IV (n=14), via catheter or drain (n=4), oral administration (n=7), and locally (n=1). Several routes of administration, including topical, catheter, rectal, and intrathoracic administrations were provided for 1 patient each.
The median titer of phage administered was 109 PFU/mL (IQR 108-109 PFU/mL) given at a frequency from hourly to daily, with no instances of single administration. The median treatment duration was 15 days (IQR 7-42). A total of 43 patients had phage therapy concurrent with antibiotic therapy.
Out of 54 patients, 68% experienced clinical improvement (37/54), while 63% showed total eradication of pathogens (34/54). Three patients experienced adverse reactions to phage therapy, transient fever [53], cytokine storm [46], and coughing during nebulized administration [9]. No other adverse events were linked to therapy.

3.5.4. Native Osteoarticular Infections

A total of 40 patients across 10 studies [9,31,35,38,44,61,62,63,64,65] were given phage therapy for osteomyelitis (37 patients), septic arthritis (2 patients), and joint infection (1 patient). The pathogens involved in these cases included S. aureus (n=22), P. aeruginosa (n=15), S. epidermidis (n=3), E. faecalis (n=3), K. pneumoniae (n=2), B. fragilis (n=1), and A. baumannii (n=1), E. coli (n=1). Patients with these infections were given phage therapy primarily by drain or catheter (n=13), intraoperatively (n=13), IV (n=12), topically (n=4), locally (n=10), orally (n=2).
The median titer of phage administered was 107 PFU/mL (IQR 107-109 PFU/mL). Phages were administered over a range of every 8 hours to four times a year. The median treatment duration was 14 days (IQR 10-28). All but one patient received phage with concurrent antibiotics. 15 patients received therapy as a part of a surgical intervention, with all but one of these patients showing clinical improvement.
Out of 40 patients who received phage therapy for native osteoarticular infections, 83% experienced clinical improvement (33/40), while 58% showed total eradication of pathogens (23/40). Four patients experienced adverse events: local irritation and pain [63], one fever [9], one experiencing dizziness and fatigue, and another experiencing transaminitis and leukopenia [31]. No other adverse events were linked to therapy.

3.5.5. Orthopedic Hardware

A total of 53 patients across 20 studies [9,31,35,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82] were given therapy for difficult-to-treat orthopedic hardware infections with phage. All but one of these infections were prosthetic joint infections, with one allograft infection. The pathogens involved in these cases included Staphylococcus spp. (n=28), S. aureus (n=12), P. aeruginosa (n=6), S. epidermidis (n=3), K. pneumoniae (n=2), E. faecalis (n=2), E. coli (n=1). Patients with these infections were given phage intraoperatively (n=45) or via drain or catheter (n=29), IV (n=16), local application (n=5), orally (n=1), intra-arterial (n=1), topically (n=1).
The median titer of phage administered was 107 PFU/mL (IQR 105-109 PFU/mL). This was administered over a range of every 8 hours to daily. Eight patients received a single treatment. Excluding one-time treatments, the median treatment duration was 10 days (IQR 5-10). All but two patients received concurrent antibiotic therapy. All but four patients received phage therapy as a part of surgical revision.
Out of 53 patients, 92% experienced clinical improvement (49/53), while 87% showed total eradication of pathogens (40/46). Ten patients experienced adverse reactions, 4 fever (one patient with local pain as well) [9,75,80] and 6 elevated transferase concerns [68,77,78,82]. No other adverse events were linked to therapy.

3.5.6. Cardiac Hardware

A total of 26 patients across 16 studies [9,31,38,44,83,84,85,86,87,88,89,90,91,92,93,94] were given therapy for difficult-to-treat cardiac device and vascular graft infections: infected grafts (8 patients), LVADs (12), and prosthetic valves (6). The pathogens involved in these cases included S. aureus (n=16), P. aeruginosa (n=11), E. coli (n=1), C. acnes (n=1), E. faecium (n=1), and P mirabilis (n=1).
Patients with these infections were given phage via IV (n=16), intraoperatively (n=9), via drain or catheter (n=9), orally (n=2), topically (n=2), and intranasally (n=1). The median titer of phage administered was 109 PFU/mL (IQR 107-109 PFU/mL) with a range of every 8 hours to daily. Four patients received one time treatment. Excluding one-time treatments, the median treatment duration was 14 days (IQR 7-25). All patients received concurrent antibiotic therapy. 14 patients received therapy as a part of surgical revision, with all but 1 of these patients experiencing clinical improvement.
Out of 26 patients, 60% experienced clinical improvement (18/26), while 65% showed total eradication of pathogens (17/26). One patient experienced shortness of breath and fever at 1011 PFU/mL which was well tolerated with a log reduction of dose, suggesting concentration dependent adverse event relationship [88]. Two patients experienced fever, with one of these patients experiencing multiple recurring fevers [31]. No other adverse events were linked to therapy.

3.5.7. Genitourinary Infections

32 patients across 9 studies were treated for genitourinary infections with phage [50,88,95,96,97,98,99,100,101]. Most of these patients were treated as a part of a UTI clinical trial Kim et al. with 24 patients with per-patient information. Patients were treated primarily for UTI (n=29), transplant related infection (n=2), and vaginitis (n=1). The pathogens involved in these cases were E. coli (n=26), K. pneumonia (n=4), E. faecalis (n=1), P. aeruginosa (n=6), S. epidermidis (n=3), E. faecalis (n=2), K. pneumonia (n=2), E. coli (n=1), S. aureus (n=1).
Patients were treated for these infections with IV (n=27), via drain or catheter (n=16), oral (n=5), per rectum (n=3), and vaginal suppositories (n=1). The median titer of phage administered was 1012 PFU/mL (IQR 1011-1012 PFU/mL) with a range of twice a day to q24h. Treatment lasted a median of 4 days (IQR 3 – 6 days) with all but 2 patients receiving concurrent antibiotic treatment.
Out of 32 patients, 69% experienced clinical improvement (22/32) while 56% experienced pathogenic eradication (18/32). 7 patients all in the Kim et al. study experienced mild transient tachycardia and afebrile chills. Notably, this study had 9 patients which had therapy withdrawn due to safety signal before intravenous titer was reduced by a log due to these adverse events. After the reduction of titer, therapy was well tolerated [95]. No adverse events were otherwise noted.

3.5.8. Upper Respiratory

A total of 29 patients across 5 studies [9,31,32,35,102] were given therapy for difficult-to-treat head and neck infections. 18 patients presented as sinusitis, 10 patients as rhinosinusitis, with 1 patient presenting with a skin infection with nasal colonization. The pathogens involved in these cases included S. aureus (n=24), P. aeruginosa (n=5), and A. xylosoxidans (n=2).
Patients with these infections were given therapy primarily intranasally (n=25), but also orally (n=4), locally (n=4), and via IV (n=1).
The median titer of phage administered was 107 PFU/mL (IQR 107-108 PFU/mL) with a range of every 8 hours to daily. The median treatment duration was 21 days (IQR 14-21). 28% of patients received concurrent antibiotic therapy (8/29). None of these interventions were associated with surgical revision.
Out of 29 patients, 69% experienced clinical improvement (20/29), while only 27% experienced eradication of pathogen (8/29). One patient experienced an adverse reaction of lip rash with a possible link to therapy while one patient experienced abdominal discomfort [9].

3.5.9. Otitis

A total of 14 patients across 3 studies [103] were given therapy for ear infections. Wright et al. reported that 12 patients were treated for P. aeruginosa ear infections with intra-otic administration of a phage cocktail in a randomized clinical trial [31,103]. Treatment was given on day 1 of the study. Out of these 12 patients, 91% experienced clinical improvement (11/12) by 6 weeks and 25% experienced bacterial eradication. No adverse events were attributed to therapy. Two other successful cases of otitis treatment were documented in Onallah et al, with IV phage therapy with a titer of 1010 PFU/mL – 1011 PFU/mL was given to patients suffering from P. aeruginosa infections over the span of 8 – 10 days[31].

3.5.10. Native Infective Endocarditis

5 patients across 3 studies [44,104,105] were treated for bloodstream infections secondary to endocarditis with intravenous phage administration. One patient died during surgical intervention [44] but this was not attributed to phage therapy, while all others fully recovered with no adverse effects.

3.5.11. Abdominal Infections

8 patients across 4 studies [9,31,106,107,108] were treated for abdominal infections with phage. 6 patients fully recovered with clearance of pathogen while one patient died from their illness during treatment. One patient that experienced leukopenia and vasopressor dependency died, though this was not linked to phage therapy [31]. No adverse events were noted.

3.5.12. Other

2 patients were treated for hardware infections that could not be categorized as either cardiac or orthopedic [9,38], both experiencing clinical improvement and eradication of bacteria without adverse events. 3 patients were treated for non-specific systemic bacteremia, with one patient making a full recovery [109], one patient experiencing clinical improvement but persistent infection [110], and one patient died from their illness [111]. Only 1 patient was treated for a central nervous system infection with phage and died from their illness during treatment [112].

3.5.13. Phage Formulations

A total of 144 patients across 29 studies [9,32,33,35,36,41,42,43,44,45,50,63,65,76,80,84,85,86,88,90,91,92,95,96,103,104,106,108,111] received phage therapy using only fixed (off-the-shelf) cocktails. Of these 144 patients, 75 experienced bacterial eradication (52%) and 109 experienced clinical improvement (76%). In contrast 179 patients across 59 studies [34,35,37,38,40,42,46,47,48,49,50,51,52,61,62,64,66,67,68,69,71,72,73,74,75,77,82,83,87,88,89,97,98,99,102,107,110,112] received bespoke phage preparations formulated de novo for the patient and infection in question. Out of these, 102 experienced bacterial eradication (57%) and 144 experienced clinical improvement (80%). 6 patients were given a phage genetically engineered against the patient isolate [50,52,97,110], 2 of which had total bacterial eradication while 5 experienced clinical improvement. (Figure 7).

4. Discussion

We performed a systematic review of personalized phage therapy cases reported in the peer-reviewed, English-language literature for which individual patient data were available. Together, these data indicate that there is substantial heterogeneity in the current clinical practices involved in personalized phage therapy. However, several patterns emerge from this analysis.
Most patients who received personalized phage were treated with phage cocktails. This is consistent with extensive in vitro and in vivo data supporting the use of phage cocktails to prevent the emergence of resistant isolates [18,19,20,21].
Most patients received antibiotics concurrently with phage therapy. This is consistent with use of phages as an adjunctive treatment superimposed upon the standard of care in many cases. As with phage cocktails, is it also supported by extensive in vitro and in vivo data [22,23]. 144 patients received fixed (off-the-shelf) phage preparations whereas 179 received bespoke phage preparations. The rates of bacterial eradication were similar for these groups, though it is difficult to draw many conclusions from this given the heterogenous formulations and practices involved at each facility.
Most phage therapy is administered over a relatively narrow range of phage concentrations in these cases (median 108 PFU/mL; IQR 107-109).
In contrast, there was more heterogeneity regarding the route, frequency, and duration of phage administration, reflecting the many different indications and pathogens targeted by these treatments.
For cases where outcomes data were available, 78% (253/323), experienced clinical improvement following phage therapy while the targeted pathogen was eradicated in 61% (177/290) of cases. These numbers agree with the other recent reviews of the literature. Uyttebrook et al. examined 59 published studies prior to 2021 and reported a bacterial eradication rate of 87% and clinical improvement rate of 79% [28]. However, negative trials are less likely to be published, and the results may overly represent good outcomes.
Another assessment of personalized phage therapy efficacy should be drawn from the comprehensive report from the Belgian consortium (Queen Astrid Military Hospital) of 100 consecutive patients who received magistral therapy. They reported a bacterial eradication rate of 61% and a clinical improvement rate of 77% [9]. Of note, the present study of 323 cases includes 85 of these Belgian patients; when the remaining 238 patients are directly compared with Belgium, we find a similar eradication rate of 62% (137/222, reported) and 80% (190/238) clinical improvement rate. Taken together, these results are highly encouraging, particularly when one considers that phages are typically only used as salvage therapy in patients who have failed conventional antibiotic regimens.
Our review has multiple limitations in addition to the publication bias noted above. This dataset is a small and heterogenous. Moreover, 100 of these cases come from a single case series (Pirnay et al,) Additional randomized controlled trials are needed to better identify best practices. The definition of “clinical improvement” is also heterogeneous and includes patients with appreciable clinical effect as well as complete cure. Many key details were missing from these reports. For example, the actual total dose given to patients was missing in some reports. We encourage development of a phage therapy reporting standard to assess future case reports to address these concerns.
Despite these limitations the data presented here provides an encouraging snapshot of personalized phage therapy. There is clearly room for improvement but the fundamental outstanding questions in the field are clear.

Supplementary Materials

The following supporting information can be downloaded at the website of this paper posted on Preprints.org.

Acknowledgments

This work was supported by grants KL2TR003143, R21AI133370, R21AI133240, R01AI12492093, P01AI1960471, K24 AI166718, R01 AI182349-01A1, R01EB038154, and grants from Stanford SPARK, the Falk Medical Research Trust, the Orthopedic Research and Education Foundation (OREF), and the Cystic Fibrosis Foundation (CFF).

Conflicts of Interest

The authors declare no conflict of interest.

Abbreviations

Food and Drug Administration (FDA); European Medicines Agency (EMA); Good Manufacturing Practice (GMP); Intravenous (I.V.); Intraperitoneal (I.P.); Oral (P.O.); Intramuscular (I.M.); Infusion related reactions (IRR); Endotoxin release (ER); Erythrocyte sedimentation rate (ESR); C-reactive protein (CRP); Endotoxin units (EU); Bacteriophage therapy (BT); Plaque forming units (PFU); Every 24 hours (q24h); Every 8 hours (q8h); Every 12 hours (q12h); Species (spp.)

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Figure 1. PRISMA 2020 flow diagram illustrating the study selection process. Adapted from Page MJ, et al. BMJ 2021;372. doi: 10.1136/bmj.n71. Used under the terms of the Creative Commons Attribution License (CC BY 4.0).
Figure 1. PRISMA 2020 flow diagram illustrating the study selection process. Adapted from Page MJ, et al. BMJ 2021;372. doi: 10.1136/bmj.n71. Used under the terms of the Creative Commons Attribution License (CC BY 4.0).
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Figure 2. Data Describing Patient Demographics, Indications, and Pathogens. a) Distribution of patients by sex and age for the 119 patients in this dataset for whom exact age was available.
Figure 2. Data Describing Patient Demographics, Indications, and Pathogens. a) Distribution of patients by sex and age for the 119 patients in this dataset for whom exact age was available.
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Figure 3. Graphic comparing the number of patients afflicted with a given bacterial species. On the X-axis, the type of bacterial species. On the y-axis, the count of how many patients were affected by the given bacterial species. Note the total number shown exceeds 323 patients due to polyclonal infections.
Figure 3. Graphic comparing the number of patients afflicted with a given bacterial species. On the X-axis, the type of bacterial species. On the y-axis, the count of how many patients were affected by the given bacterial species. Note the total number shown exceeds 323 patients due to polyclonal infections.
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Figure 4. Distribution of phage route administrations. The total number exceeds the number of patients as some patients received phage via more than 1 route.
Figure 4. Distribution of phage route administrations. The total number exceeds the number of patients as some patients received phage via more than 1 route.
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Figure 5. Description of phage adverse events. A. The number and B. type of adverse events is shown. Overall, 292 of the 323 cases (90%) evaluated here were well-tolerated without adverse events.
Figure 5. Description of phage adverse events. A. The number and B. type of adverse events is shown. Overall, 292 of the 323 cases (90%) evaluated here were well-tolerated without adverse events.
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Figure 6. Bacterial eradication rates following phage therapy grouped by indication. On the X axis the different indications are shown while on the y axis the number of patients for that infectious group are shown. Data are shown for the number of cases successfully eradicated (blue), cases where the infection persisted (red), cases where the outcome was unknown (green), and cases where therapy was withdrawn before an outcome could be determined due to safety signal(gray).
Figure 6. Bacterial eradication rates following phage therapy grouped by indication. On the X axis the different indications are shown while on the y axis the number of patients for that infectious group are shown. Data are shown for the number of cases successfully eradicated (blue), cases where the infection persisted (red), cases where the outcome was unknown (green), and cases where therapy was withdrawn before an outcome could be determined due to safety signal(gray).
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Figure 7. Graphic comparing the clinical outcomes of patients by the selection criteria for the phage therapy. A: outcome determined by clinical improvement. B: outcome determined by bacterial eradication.
Figure 7. Graphic comparing the clinical outcomes of patients by the selection criteria for the phage therapy. A: outcome determined by clinical improvement. B: outcome determined by bacterial eradication.
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Copyright: This open access article is published under a Creative Commons CC BY 4.0 license, which permit the free download, distribution, and reuse, provided that the author and preprint are cited in any reuse.
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