Patient 1 was a 33-year-old male with high-risk refractory acute myeloid leukemia (AML) who developed neutropenia after chemotherapy. On June 2, 2024, the patient presented with chills and fever, with a maximum temperature (Tmax) of 39 °C. NGS of the peripherally inserted central catheter (PICC) revealed Klebsiella michiganensis (sequence count: 3108, resistance genes KPC-9 and CTX-M-159) and Enterobacter cloacae complex (sequence count: 39). Concurrent chest computed tomography (CT) indicated bilateral pneumonia. NGS of the patient's sputum detected Escherichia coli (sequence count 837) with resistance genes NDM, KPC, and CTX-M. On June 4, 2024, the PICC catheter was removed, and colistin and tigecycline were initiated to treat the patient's infection. On June 6, a blood culture from the catheter showed Klebsiella oxytoca: +++, and antimicrobial susceptibility results indicated the presence of extended-spectrum beta-lactamase, with resistance to piperacillin-tazobactam, cephalosporins, meropenem, and imipenem. The minimum inhibitory concentration value for tigecycline is 1 mg/mL. According to EUCAST breakpoints, the isolate was classified as resistant to tigecycline. By June 8, the patient developed two red, indurated nodules on the right lower limb, the largest measuring 10 cm in diameter and associated with tenderness (Fig. 2A). Given the progression of the bloodstream infection with cutaneous dissemination, the antibiotic regimen was empirically adjusted to ceftazidime-avibactam, aztreonam, daptomycin and caspofungin. On June 9, the patient experienced recurrent fever, with a maximum oral temperature of 38.3 °C, accompanied by limb soreness. Despite ongoing treatment with ceftazidime-avibactam, aztreonam, daptomycin, and caspofungin, the fever persisted, suggesting an uncontrolled infection. Consequently, antibiotic regimens were modified to include colistin, eravacycline, fosfomycin, and daptomycin. Eravacycline was administered at a dose of 1 mg/kg every 12 h via intravenous infusion [12]. The patient’s temperature stabilized on the same day after adjustment of the treatment regimen.

The patient continued the combination therapy of eravacycline, colistin, fosfomycin, and daptomycin for 10 days, during which the oral temperature remained around 36.5 °C without fever (Fig. 1). Specific patient data are shown in Table 1. The red nodules on the right lower limb gradually diminished in size (Fig. 2B) (the observed improvement occurred under combined antibacterial and antifungal therapy, making attribution to a specific treatment or pathogen difficult. However, considering the combination of sepsis and blood culture results, clinical manifestations of skin lesions, and treatment response, it is more likely to be bacterial.). Subsequently, the patient’s blood count recovered, and he was discharged without further complications.

Temperature fluctuation curve of patient case 1

Changes in a typical disseminated infection of the lower limb skin before and after treatment. A Two tender, reddened indurated nodules (maximal diameter 10 cm) appeared on the right lower limb; B the indurated gradually regressed following treatment (the observed improvement occurred under combined antibacterial and antifungal therapy, making attribution to a specific treatment or pathogen difficult. However, considering the combination of sepsis and blood culture results, clinical manifestations of skin lesions, and treatment response, it is more likely to be bacterial)

The patient was a 22-year-old male with T-lymphoblastic lymphoma or acute T-lymphoblastic leukemia who experienced a relapse more than 1 year post-transplantation. He had a history of bloodstream infection with Klebsiella aerogenes and was found to have Klebsiella aerogenes colonization on rectal swab screening. On March 17, 2024, during the neutropenic phase following chemotherapy, the patient developed a fever and perianal pain. Peripheral blood NGS revealed Klebsiella aerogenes (resistance genes NDM-6 and SHV-12) with a sequence count of 481, indicating resistance to imipenem, ceftazidime, and meropenem. Tigecycline and colistin E treatment was initiated. However, the patient's fever remained uncontrolled, and on March 21, the antibiotic regimen was escalated to eravacycline, daptomycin, and colistin E owing to persistent fever and worsening perianal pain [13]. On March 25, the patient’s temperature spiked again, reaching a maximum of 39.9 °C. On March 26, the antibiotic regimen was adjusted to ceftazidime-avibactam, aztreonam, daptomycin, eravacycline, and amphotericin B, which successfully controlled the fever. Antimicrobial susceptibility testing on March 29 indicated monobactams and second-generation cephalosporins resistance with sensitivity toceftazidime-avibactam, polymyxin B, gentamicin, and tobramycin. and owing to financial constraints, eravacycline was discontinued, and the antibiotic regimen was adjusted to ceftazidime-avibactam combined with amikacin.

On April 9, 2024, the patient experienced recurrent fever and occasional right upper quadrant abdominal pain. Abdominal magnetic resonance imaging (MRI) on April 10 revealed multiple abscesses in the liver and spleen. Peripheral blood NGS on April 10 detected Klebsiella aerogenes (resistance genes NDM-18 and SHV-64) with a sequence count of 51,544. The patient again developed a bloodstream infection with dissemination to the liver and spleen. On April 11, the antibiotic regimen was adjusted to a previously sensitive combination of ceftazidime-avibactam, aztreonam, and eravacycline, along with intravenous immunoglobulin to enhance immunity [12]. The patient's fever decreased on the fourth day of treatment (Fig. 3) and was controlled from the fifth day onward (Table 2).

Temperature fluctuation curve of patient case 2

Imaging showed a reduction in splenic lesions 9 days after eravacycline treatment. On April 28, peripheral blood NGS did not reveal Klebsiella aerogenes. On April 29, contrast-enhanced MRI revealed varying degrees of reduction in the liver and spleen lesions (Fig. 4).

MRI of the abdomen. A Abdomen MRI on April 2, 2024, shows multiple signal abnormalities in the right and left lobes of the liver and spleen, revealing the abscesses. B Follow-up MRI on April 10 showed the lesions have expanded in size compared to the previous film. C The examination on April 19, 2024, continued to indicate multiple abscesses in the liver parenchyma and spleen. D The examination on April 29, 2024, showed that the splenic lesions were smaller. MRI magnetic resonance imaging

A 55-year-old middle-aged female experienced an AML relapse more than 10 months after transplantation. On March 16, 2024, she underwent reinduction chemotherapy. During the neutropenic phase, piperacillin-tazobactam combined with posaconazole was administered for infection prophylaxis. On March 28, 2024, during the post-chemotherapy bone marrow suppression period, the patient developed a fever with a maximum temperature (Tmax) of 39.3 °C. Peripheral blood NGS on March 29 revealed an Enterobacter cloacae complex with 2917 sequences. Antimicrobial susceptibility testing on April 5 indicated carbapenem resistance with sensitivity to amikacin, polymyxin B, and gentamicin. Based on the susceptibility results, treatment was adjusted to polymyxin E plus tigecycline for infection control.

Despite the treatment, the patient continued to experience recurrent fever, with a Tmax of 39.1 °C. Peripheral blood NGS on April 10 revealed the Enterobacter cloacae complex (resistance genes: NDM-5 and DHA-17) with 152,096 sequences, indicating resistance to imipenem, ceftazidime, and piperacillin. The patient developed renal dysfunction with a creatinine clearance rate of 30.56 mL/min, prompting the discontinuation of polymyxin E and the initiation of ceftazidime-avibactam, aztreonam, and posaconazole [14]. On April 11, the patient had a temperature of 38.5 °C and exhibited dull pain and tenderness in the liver area. Following consultation with the radiology department, abdominal contrast-enhanced CT revealed multiple small liver abscesses, suspected to be of bacterial origin. The patient was diagnosed with a bloodstream infection with hepatic dissemination, and eravacycline was added to the regimen. The treatment was adjusted to eravacycline, ceftazidime-avibactam, and aztreonam, with the patient's axillary temperature fluctuating between 37.5 and 38.2 °C. By April 16, the patient's renal function improved, and the anti-infection regimen was changed to polymyxin E plus eravacycline, resulting in normalization of the patient's temperature.

On April 21, the patient developed fever with chills again, with a Tmax of 39.7 °C. Abdominal MRI revealed multiple small liver abscesses. Peripheral blood NGS on April 22 revealed an Enterobacter cloacae complex (resistance genes: NDM-24, DHA-6, etc.) with 8,855 sequences, and procalcitonin (PCT) levels were elevated at 13.9 ng/mL. A throat swab culture also showed extensive growth of a drug-resistant Enterobacter cloacae complex, with susceptibility to eravacycline, gentamicin, amikacin, polymyxin B, and fosfomycin sodium. Based on the susceptibility results, treatment was adjusted to eravacycline, polymyxin E, and fosfomycin sodium on April 25. The patient's PCT levels decreased (Table 3), and her temperature normalized by the fourth day of the adjusted treatment (Fig. 5). On May 2 (1 week later), abdominal contrast-enhanced MRI showed a reduction in the size of the liver abscess. By May 15 (3 weeks later), abdominal contrast-enhanced MRI revealed significant resolution of multiple liver lesions (Fig. 6) (the observed radiological improvement occurred under combined antibacterial and antifungal therapy, making attribution to a specific treatment or pathogen difficult. However, considering the combination of sepsis and blood culture results and treatment response, it is more likely to be bacterial.).

Temperature fluctuation curve of patient case 3

A Abdominal contrast-enhanced CT on April 11, 2024, showed multiple small liver abscesses. B Follow-up Contrast-enhanced abdominal MRI on April 20 revealed multiple liver lesions, suggestive of small abscesses, along with gallstones. C On May 2, 2024, Contrast-enhanced abdominal MRI demonstrated multiple small liver abscesses with thickened walls and slightly reduced abscess cavities compared to previous imaging. D On May 15, Contrast-enhanced abdominal MR indicated significant resolution of multiple liver lesions (the observed radiological improvement occurred under combined antibacterial and antifungal therapy, making attribution to a specific treatment or pathogen difficult. However, considering the combination of sepsis and blood culture results and treatment response, it is more likely to be bacterial.)