A 70-year-old Japanese male who is currently receiving outpatient treatment for multiple myeloma at another hospital was admitted to our hospital for lower leg edema and nephrotic syndrome. His medical history included multiple myeloma (Durie-Salmon stage III), chronic kidney disease, type 2 diabetes mellitus (30 years), hypertension, dyslipidemia, benign prostatic hyperplasia, psoriasis vulgaris, and herpes zoster infection. Chemotherapy was administered every 5 weeks for multiple myeloma, and the most recent course was one month prior (course 26). The chemotherapy regimen consisted of oral administration of dexamethasone 10 mg on days 1, 2, 8, and 9; POM from day to 1–14, and bortezomib on days 1 and 8. He was administered with sulfamethoxazole 400 mg/trimethoprim 80 mg once daily to prevent Pneumocystis pneumonia. He had no known allergies to medication or food.
At the time of admission, there were no subjective symptoms; however, on the fourth day of hospitalization, the patient presented with fever, chills, and pain at the right thigh. The physical examination findings are as follows: body temperature of 36.9 ºC, heart rate of 65 beats per minute, respiratory rate of 18 breaths per minute, and blood pressure of 120/66 mmHg. The patient was in good general condition. Faint erythema, swelling, warmth, and tenderness were observed in the right thigh and front of the lower leg. Snowball crepitations were not observed. No petechiae, purpura, bullae, or vesicles were observed. Edema with indentation was observed in both lower legs. No other physical abnormalities, including findings suggestive of endocarditis, were observed.
Laboratory findings revealed elevated C-reactive protein level and decreased white blood cell count at 1.3×103/µL. The results of the other blood and urine tests are presented in Table 1. Computerized tomography scans did not reveal any abnormalities in the lungs, liver, gallbladder, pancreas, spleen, or intestine.
Table 1
Results of blood and urine tests on the fourth day of hospitalization with fever.
| Blood test | | Urine test (qualitative) |
| C-reactive protein | 5.6 | mg/L | | Glucose | 3+ |
| Urea nitrogen | 23 | mg/dL | | Protein | 3+ |
| Creatinine | 1.61 | mg/dL | | Occult blood | 2+ |
| Urine acid | 5.5 | mg/dL | | Urinary sediments | |
| Aspartate aminotransferase | 31 | U/l | | White blood cell (Cell/ High Power Field) | 10–19 |
| Alanine aminotransferase | 20 | U/l | | Red blood cell (Cell/High Power Field) | 1–4 |
| Lactate Dehydrogenase | 333 | U/l | | | |
| Alkaline Phosphatase | 48 | U/l | | | |
| Glutamyl transpeptidase | 15 | U/l | | | |
| Creatine kinase | 157 | U/dl | | | |
| Hemoglobin A1c | 5.9 | % | | | |
| White blood cell | 1.3 | ×103/µl | | | |
| Red blood cell | 3.57 | ×10༖/µl | | | |
| Haemoglobin | 10 | g/dl | | | |
| Hematocrit | 29.6 | % | | | |
| Platelet | 109 | ×103/µl | | | |
| Basophil | 0 | % | | | |
| Eosinophil | 0 | % | | | |
| Lymphocyte | 18.7 | % | | | |
| Monocyte | 18.7 | % | | | |
| Neutrophil | 62.6 | % | | | |
| Prothrombin time | 147 | % | | | |
| Activated partial thromboplastin time | 27.3 | sec | | | |
| Fibrinogen quantity | 741 | mg/dL | | | |
| D-dimer | 6.1 | µg/mL | | | |
| Immunoglobulin G | 313 | mg/dL | | | |
| Immunoglobulin A | 57 | mg/dL | | | |
| Immunoglobulin M | 11 | mg/dL | | | |
It was considered that there are humoral and cellular immunodeficiencies due to multiple myeloma and dexamethasone administration. Cellulitis was suspected based on skin findings, vital signs, and the patient’s general condition. Owing to the low neutrophil count and the prospective further decline, meropenem was initiated for febrile neutropenia after blood cultures were submitted.
The next day, gram-negative rods were detected in two sets of aerobic blood culture bottles. Bacterial colonies were initially small, smooth, and wrinkled after 24 h of incubation (Fig. 1). Biochemical characteristics were determined using the DxM Microscan WalkAway system (Beckman Coulter, Brea, CA, USA), which identified P. putida/fluorescens based on a high identification score of 99.99%. Conversely, Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) using MALDI Biotyper (Bruker Daltonics GmbH, Bremen, Germany) from the colony identified as P. otitidis with a high score of 2.29.
Carbapenem resistance was predicted based on previous reports on P. otitidis, and meropenem was substituted with cefepime and levofloxacin. Minimum inhibitory concentrations (MICs) were determined using the broth microdilution method according to the Clinical and Laboratory Standards Institute (CLSI) M07 tenth edition [6]. The results of the antimicrobial susceptibility testing are shown in Table 2. Although MIC of meropenem was found to be high and that of imipenem was relatively high (4 µg/mL), the MIC of penicillin and cephalosporin antibiotics were found to be low. The ciprofloxacin MIC was low (Table 2). The production of carbapenemase and MBL was confirmed using the modified carbapenem inactivation method and the double disk synergy test with sodium mercaptoacetate, respectively [7, 8]. Combination therapy with cefepime and levofloxacin was administered for two weeks to avoid the acquisition of resistance to levofloxacin during the two-week treatment period for bacteremia. Blood cultures obtained on the 5th day after the first positive blood culture were negative. The patient's condition improved and there was no recurrence of cellulitis or bacteremia thereafter.
Table 2
Results of drug susceptibility testing for isolated P. otitidis. It showed resistance to meropenem, while being susceptible to penicillin, cephalosporin, aminoglycoside, and quinolone.
| Antibiotics | MIC (µg/mL) |
| Piperacillin | <= 8 |
| Sulbactam/Ampicillin | > 32 |
| Tazobactam/piperacillin | <= 8 |
| Ceftazidime | <= 4 |
| Cefepime | <= 4 |
| Imipenem | 4 |
| Meropenem | > 8 |
| Gentamicin | <= 1 |
| Amikacin | <= 4 |
| Minocycline | 2 |
| Ciprofloxacin | <= 0.25 |
| Aztreonam | 4 |
| Sulfamethoxazole-Trimethoprim | <= 20 |